المؤلفون: Hill F. Ip, Camiel M. van der Laan, Eva M. L. Krapohl, Isabell Brikell, Cristina Sánchez-Mora, Ilja M. Nolte, Beate St Pourcain, Koen Bolhuis, Teemu Palviainen, Hadi Zafarmand, Lucía Colodro-Conde, Scott Gordon, Tetyana Zayats, Fazil Aliev, Chang Jiang, Carol A. Wang, Gretchen Saunders, Ville Karhunen, Anke R. Hammerschlag, Daniel E. Adkins, Richard Border, Roseann E. Peterson, Joseph A. Prinz, Elisabeth Thiering, Ilkka Seppälä, Natàlia Vilor-Tejedor, Tarunveer S. Ahluwalia, Felix R. Day, Jouke-Jan Hottenga, Andrea G. Allegrini, Kaili Rimfeld, Qi Chen, Yi Lu, Joanna Martin, María Soler Artigas, Paula Rovira, Rosa Bosch, Gemma Español, Josep Antoni Ramos Quiroga, Alexander Neumann, Judith Ensink, Katrina Grasby, José J. Morosoli, Xiaoran Tong, Shelby Marrington, Christel Middeldorp, James G. Scott, Anna Vinkhuyzen, Andrey A. Shabalin, Robin Corley, Luke M. Evans, Karen Sugden, Silvia Alemany, Lærke Sass, Rebecca Vinding, Kate Ruth, Jess Tyrrell, Gareth E. Davies, Erik A. Ehli, Fiona A. Hagenbeek, Eveline De Zeeuw, Toos C.E.M. Van Beijsterveldt, Henrik Larsson, Harold Snieder, Frank C. Verhulst, Najaf Amin, Alyce M. Whipp, Tellervo Korhonen, Eero Vuoksimaa, Richard J. Rose, André G. Uitterlinden, Andrew C. Heath, Pamela Madden, Jan Haavik, Jennifer R. Harris, Øyvind Helgeland, Stefan Johansson, Gun Peggy S. Knudsen, Pal Rasmus Njolstad, Qing Lu, Alina Rodriguez, Anjali K. Henders, Abdullah Mamun, Jackob M. Najman, Sandy Brown, Christian Hopfer, Kenneth Krauter, Chandra Reynolds, Andrew Smolen, Michael Stallings, Sally Wadsworth, Tamara L. Wall, Judy L. Silberg, Allison Miller, Liisa Keltikangas-Järvinen, Christian Hakulinen, Laura Pulkki-Råback, Alexandra Havdahl, Per Magnus, Olli T. Raitakari, John R. B. Perry, Sabrina Llop, Maria-Jose Lopez-Espinosa, Klaus Bønnelykke, Hans Bisgaard, Jordi Sunyer, Terho Lehtimäki, Louise Arseneault, Marie Standl, Joachim Heinrich, Joseph Boden, John Pearson, L. John Horwood, Martin Kennedy, Richie Poulton, Lindon J. Eaves, Hermine H. Maes, John Hewitt, William E. Copeland, Elizabeth J. Costello, Gail M. Williams, Naomi Wray, Marjo-Riitta Järvelin, Matt McGue, William Iacono, Avshalom Caspi, Terrie E. Moffitt, Andrew Whitehouse, Craig E. Pennell, Kelly L. Klump, S. Alexandra Burt, Danielle M. Dick, Ted Reichborn-Kjennerud, Nicholas G. Martin, Sarah E. Medland, Tanja Vrijkotte, Jaakko Kaprio, Henning Tiemeier, George Davey Smith, Catharina A. Hartman, Albertine J. Oldehinkel, Miquel Casas, Marta Ribasés, Paul Lichtenstein, Sebastian Lundström, Robert Plomin, Meike Bartels, Michel G. Nivard, Dorret I. Boomsma

المصدر: Translational Psychiatry, Vol 11, Iss 1, Pp 1-9 (2021)

مصطلحات موضوعية: Neurosciences. Biological psychiatry. Neuropsychiatry, RC321-571

الوصف: Abstract Childhood aggressive behavior (AGG) has a substantial heritability of around 50%. Here we present a genome-wide association meta-analysis (GWAMA) of childhood AGG, in which all phenotype measures across childhood ages from multiple assessors were included. We analyzed phenotype assessments for a total of 328 935 observations from 87 485 children aged between 1.5 and 18 years, while accounting for sample overlap. We also meta-analyzed within subsets of the data, i.e., within rater, instrument and age. SNP-heritability for the overall meta-analysis (AGGoverall) was 3.31% (SE = 0.0038). We found no genome-wide significant SNPs for AGGoverall. The gene-based analysis returned three significant genes: ST3GAL3 (P = 1.6E–06), PCDH7 (P = 2.0E–06), and IPO13 (P = 2.5E–06). All three genes have previously been associated with educational traits. Polygenic scores based on our GWAMA significantly predicted aggression in a holdout sample of children (variance explained = 0.44%) and in retrospectively assessed childhood aggression (variance explained = 0.20%). Genetic correlations (r g ) among rater-specific assessment of AGG ranged from r g = 0.46 between self- and teacher-assessment to r g = 0.81 between mother- and teacher-assessment. We obtained moderate-to-strong r g s with selected phenotypes from multiple domains, but hardly with any of the classical biomarkers thought to be associated with AGG. Significant genetic correlations were observed with most psychiatric and psychological traits (range $$\left| {r_g} \right|$$ r g : 0.19–1.00), except for obsessive-compulsive disorder. Aggression had a negative genetic correlation (r g = ~−0.5) with cognitive traits and age at first birth. Aggression was strongly genetically correlated with smoking phenotypes (range $$\left| {r_g} \right|$$ r g : 0.46–0.60). The genetic correlations between aggression and psychiatric disorders were weaker for teacher-reported AGG than for mother- and self-reported AGG. The current GWAMA of childhood aggression provides a powerful tool to interrogate the rater-specific genetic etiology of AGG.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2158-3188Test

الوصول الحر: https://doaj.org/article/882fa84e3ace4249a3c5e7bb582ea021Test

المؤلفون: Bin Qiu, Susan E. Luczak, Tamara L. Wall, Aaron M. Kirchhoff, Yuxue Xu, Mimy Y. Eng, Robert B. Stewart, Weinian Shou, Stephen L. Boehm, Julia A. Chester, Weidong Yong, Tiebing Liang

المصدر: International Journal of Molecular Sciences, Vol 17, Iss 8, p 1271 (2016)

مصطلحات موضوعية: Fkbp5 knockout, alcohol drinking behavior, human alcohol use disorder, Biology (General), QH301-705.5, Chemistry, QD1-999

الوصف: FKBP5 encodes FK506-binding protein 5, a glucocorticoid receptor (GR)-binding protein implicated in various psychiatric disorders and alcohol withdrawal severity. The purpose of this study is to characterize alcohol preference and related phenotypes in Fkbp5 knockout (KO) mice and to examine the role of FKBP5 in human alcohol consumption. The following experiments were performed to characterize Fkpb5 KO mice. (1) Fkbp5 KO and wild-type (WT) EtOH consumption was tested using a two-bottle choice paradigm; (2) The EtOH elimination rate was measured after intraperitoneal (IP) injection of 2.0 g/kg EtOH; (3) Blood alcohol concentration (BAC) was measured after 3 h limited access of alcohol; (4) Brain region expression of Fkbp5 was identified using LacZ staining; (5) Baseline corticosterone (CORT) was assessed. Additionally, two SNPs, rs1360780 (C/T) and rs3800373 (T/G), were selected to study the association of FKBP5 with alcohol consumption in humans. Participants were college students (n = 1162) from 21–26 years of age with Chinese, Korean or Caucasian ethnicity. The results, compared to WT mice, for KO mice exhibited an increase in alcohol consumption that was not due to differences in taste sensitivity or alcohol metabolism. Higher BAC was found in KO mice after 3 h of EtOH access. Fkbp5 was highly expressed in brain regions involved in the regulation of the stress response, such as the hippocampus, amygdala, dorsal raphe and locus coeruleus. Both genotypes exhibited similar basal levels of plasma corticosterone (CORT). Finally, single nucleotide polymorphisms (SNPs) in FKBP5 were found to be associated with alcohol drinking in humans. These results suggest that the association between FKBP5 and alcohol consumption is conserved in both mice and humans.

وصف الملف: electronic resource

العلاقة: http://www.mdpi.com/1422-0067/17/8/1271Test; https://doaj.org/toc/1422-0067Test

الوصول الحر: https://doaj.org/article/7a43cea1c070404ba5f4758607d453c6Test

المؤلفون: Richard Border, Robin P Corley, Sandra A Brown, John K Hewitt, Christian J Hopfer, Michael C Stallings, Tamara L Wall, Susan E Young, Soo Hyun Rhee

المصدر: PLoS ONE, Vol 13, Iss 11, p e0206442 (2018)

مصطلحات موضوعية: Medicine, Science

الوصف: Externalizing problems (EP), including rule-breaking, aggression, and criminal involvement, are highly prevalent during adolescence, but the adult outcomes of adolescents exhibiting EP are characterized by heterogeneity. Although many youths' EP subside after adolescence, others' persists into adulthood. Characterizing the development of severe EP is essential to prevention and intervention efforts. Multiple predictors of adult antisocial personality disorder (ASPD) and legal outcomes of a large sample (N = 1205) of clinically- or legally-ascertained adolescents (ages 12-19 years) with severe EP were examined. Many psychosocial predictors hypothesized to predict persistence of EP demonstrated zero-order associations with adult outcomes, but accounted for little unique variation after accounting for baseline conduct disorder symptoms (CD) and demographic factors. Baseline measures of intelligence, which explained independent variation in legal outcomes, provided the only consistent exception to this pattern, though future work is needed to parse these effects from those of socioeconomic factors. CD severity during adolescence is a parsimonious index of liability for persistence of EP into adulthood that explains outcome variance above and beyond all other demographic and psychosocial predictors in this sample.

العلاقة: http://europepmc.org/articles/PMC6211688?pdf=renderTest; https://doaj.org/toc/1932-6203Test; https://doaj.org/article/80c8f79d1cf84274844f6cd7fa947dd6Test

الإتاحة: https://doi.org/10.1371/journal.pone.0206442Test
https://doaj.org/article/80c8f79d1cf84274844f6cd7fa947dd6Test

المؤلفون: Duncan B. Clark, Sandra A. Brown, Marybel Robledo Gonzalez, Kate B. Nooner, Tamara L. Wall, Sonja C Eberson-Shumate, Alejandro D. Meruelo, Susan F. Tapert, Connor J. McCabe

المصدر: Alcoholism, clinical and experimental research, vol 45, iss 6
Alcohol Clin Exp Res

مصطلحات موضوعية: Male, 030508 substance abuse, Medicine (miscellaneous), Prospective data, Toxicology, sensation seeking, Alcohol Use and Health, Substance Misuse, 0302 clinical medicine, Models, Reward sensitivity, 2.1 Biological and endogenous factors, Psychology, Longitudinal Studies, Aetiology, Pediatric, Substance Abuse, Cognition, Statistical, Late adolescence, Alcoholism, Psychiatry and Mental health, Female, 0305 other medical science, impulse control, Clinical psychology, Change over time, Adolescent, Clinical Sciences, Sensation, Difference score, Article, Binge Drinking, dual systems, Young Adult, 03 medical and health sciences, Risk-Taking, Clinical Research, Humans, Sensation seeking, Risk factor, Models, Statistical, Prevention, Neurosciences, Adolescent Development, alcohol use, Good Health and Well Being, Adolescent Behavior, adolescence, 030217 neurology & neurosurgery

الوصف: BackgroundDual systems theories suggest that greater imbalance between higher reward sensitivity and lower cognitive control across adolescence conveys risk for behaviors such as heavy episodic drinking (HED). Prior research demonstrated that psychological analogues of these systems, sensation seeking and premeditation, change from childhood through emerging adulthood, and each has been independently linked with HED. However, few studies have assessed whether change over time in these developing analogues is prospectively associated with HED. Moreover, we know of no research that has shown whether within-person differences between higher sensation seeking and relatively lower premeditation across the adolescent period predict HED in emerging adulthood.MethodsProspective data from the National Consortium on Alcohol and NeuroDevelopment in Adolescence study (n=715) were used to examine the association of sensation seeking and premeditation with HED among adolescents ages 16 to 20years. We used novel applications of latent difference score modeling and growth curve analysis to test whether increasing sensation seeking, premeditation, and their imbalance over time are associated with HED across the study period, and whether these associations differed by sex.ResultsWhereas premeditation increased linearly from adolescence through emerging adulthood across sexes, males reported growth and females reported decline in sensation seeking. Sensation seeking in adolescence (and not premeditation) was associated with higher levels of HED by emerging adulthood. Importantly, greater imbalance between sensation seeking and premeditation was associated with higher levels of HED by emerging adulthood though we note that variability capturing this imbalance correlated highly (r=0.86) with baseline levels of sensation seeking.ConclusionsDevelopmental imbalance between higher sensation seeking and lower premeditation in late adolescence may be a risk factor for greater HED in emerging adulthood.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b3fdf11448417c5b131fb265aafcf6d0Test
https://doi.org/10.1111/acer.14604Test

المؤلفون: Emma C Johnson, Ditte Demontis, Thorgeir E Thorgeirsson, Raymond K Walters, Renato Polimanti, Alexander S Hatoum, Sandra Sanchez-Roige, Sarah E Paul, Frank R Wendt, Toni-Kim Clarke, Dongbing Lai, Gunnar W Reginsson, Hang Zhou, June He, David A A Baranger, Daniel F Gudbjartsson, Robbee Wedow, Daniel E Adkins, Amy E Adkins, Jeffry Alexander, Silviu-Alin Bacanu, Tim B Bigdeli, Joseph Boden, Sandra A Brown, Kathleen K Bucholz, Jonas Bybjerg-Grauholm, Robin P Corley, Louisa Degenhardt, Danielle M Dick, Benjamin W Domingue, Louis Fox, Alison M Goate, Scott D Gordon, Laura M Hack, Dana B Hancock, Sarah M Hartz, Ian B Hickie, David M Hougaard, Kenneth Krauter, Penelope A Lind, Jeanette N McClintick, Matthew B McQueen, Jacquelyn L Meyers, Grant W Montgomery, Ole Mors, Preben B Mortensen, Merete Nordentoft, John F Pearson, Roseann E Peterson, Maureen D Reynolds, John P Rice, Valgerdur Runarsdottir, Nancy L Saccone, Richard Sherva, Judy L Silberg, Ralph E Tarter, Thorarinn Tyrfingsson, Tamara L Wall, Bradley T Webb, Thomas Werge, Leah Wetherill, Margaret J Wright, Stephanie Zellers, Mark J Adams, Laura J Bierut, Jason D Boardman, William E Copeland, Lindsay A Farrer, Tatiana M Foroud, Nathan A Gillespie, Richard A Grucza, Kathleen Mullan Harris, Andrew C Heath, Victor Hesselbrock, John K Hewitt, Christian J Hopfer, John Horwood, William G Iacono, Eric O Johnson, Kenneth S Kendler, Martin A Kennedy, Henry R Kranzler, Pamela A F Madden, Hermine H Maes, Brion S Maher, Nicholas G Martin, Matthew McGue, Andrew M McIntosh, Sarah E Medland, Elliot C Nelson, Bernice Porjesz, Brien P Riley, Michael C Stallings, Michael M Vanyukov, Scott Vrieze, Lea K Davis, Ryan Bogdan, Joel Gelernter, Howard J Edenberg, Kari Stefansson, Anders D Børglum, Arpana Agrawal, Raymond Walters, Emma Johnson, Jeanette McClintick, Alexander Hatoum, Frank Wendt, Mark Adams, Amy Adkins, Fazil Aliev, Anthony Batzler, Sarah Bertelsen, Joanna Biernacka, Tim Bigdeli, Li-Shiun Chen, Yi-Ling Chou, Franziska Degenhardt, Anna Docherty, Alexis Edwards, Pierre Fontanillas, Jerome Foo, Josef Frank, Ina Giegling, Scott Gordon, Laura Hack, Annette Hartmann, Sarah Hartz, Stefanie Heilmann-Heimbach, Stefan Herms, Colin Hodgkinson, Per Hoffman, Jouke Hottenga, Martin Kennedy, Mervi Alanne-Kinnunen, Bettina Konte, Jari Lahti, Marius Lahti-Pulkkinen, Lannie Ligthart, Anu Loukola, Brion Maher, Hamdi Mbarek, Andrew McIntosh, Matthew McQueen, Jacquelyn Meyers, Yuri Milaneschi, Teemu Palviainen, John Pearson, Roseann Peterson, Samuli Ripatti, Euijung Ryu, Nancy Saccone, Jessica Salvatore, Melanie Schwandt, Fabian Streit, Jana Strohmaier, Nathaniel Thomas, Jen-Chyong Wang, Bradley Webb, Amanda Wills, Jason Boardman, Danfeng Chen, Doo-Sup Choi, William Copeland, Robert Culverhouse, Norbert Dahmen, Benjamin Domingue, Sarah Elson, Mark Frye, Wolfgang Gäbel, Caroline Hayward, Marcus Ising, Margaret Keyes, Falk Kiefer, John Kramer, Samuel Kuperman, Susanne Lucae, Michael Lynskey, Wolfgang Maier, Karl Mann, Satu Männistö, Bertram Müller-Myhsok, Alison Murray, John Nurnberger, Aarno Palotie, Ulrich Preuss, Katri Räikkönen, Maureen Reynolds, Monika Ridinger, Norbert Scherbaum, Marc Schuckit, Michael Soyka, Jens Treutlein, Stephanie Witt, Norbert Wodarz, Peter Zill, Daniel Adkins, Dorret Boomsma, Laura Bierut, Sandra Brown, Kathleen Bucholz, Sven Cichon, E. Jane Costello, Harriet de Wit, Nancy Diazgranados, Danielle Dick, Johan Eriksson, Lindsay Farrer, Tatiana Foroud, Nathan Gillespie, Alison Goate, David Goldman, Richard Grucza, Dana Hancock, Andrew Heath, John Hewitt, Christian Hopfer, William Iacono, Eric Johnson, Jaakko Kaprio, Victor Karpyak, Kenneth Kendler, Henry Kranzler, Paul Lichtenstein, Penelope Lind, Matt McGue, James MacKillop, Pamela Madden, Hermine Maes, Patrik Magnusson, Nicholas Martin, Sarah Medland, Grant Montgomery, Elliot Nelson, Markus Nöthen, Abraham Palmer, Nancy Pederson, Brenda Penninx, John Rice, Marcella Rietschel, Brien Riley, Richard Rose, Dan Rujescu, Pei-Hong Shen, Judy Silberg, Michael Stallings, Ralph Tarter, Michael Vanyukov, Tamara Wall, John Whitfield, Hongyu Zhao, Benjamin Neale, Howard Edenberg

المساهمون: Technology Centre, Department of Psychology and Logopedics, Developmental Psychology Research Group, University Management, HUSLAB, Genetic Epidemiology, Institute for Molecular Medicine Finland, Department of Public Health, Centre of Excellence in Complex Disease Genetics, Samuli Olli Ripatti / Principal Investigator, Complex Disease Genetics, Biostatistics Helsinki, Faculty of Arts, Research Programme of Molecular Medicine, Aarno Palotie / Principal Investigator, Genomics of Neurological and Neuropsychiatric Disorders, Research Programs Unit, Diabetes and Obesity Research Program, Department of General Practice and Primary Health Care, Johan Eriksson / Principal Investigator, Clinicum, Psychiatry, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, APH - Mental Health, APH - Digital Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Methodology

المصدر: Johnson, E, Hottenga, J, Ligthart, L, Mbarek, H, Milaneschi, Y, Boomsma, D, Agrawal, A & Psychiatric Genomics Consortium Substance Use Disorders Workgroup 2020, ' A large-scale genome-wide association study meta-analysis of cannabis use disorder ', The Lancet Psychiatry, vol. 7, no. 12, pp. 1032-1045 . https://doi.org/10.1016/S2215-0366Test(20)30339-4
Johnson, E C, Demontis, D, Thorgeirsson, T E, Walters, R K, Polimanti, R, Hatoum, A S, Sanchez-Roige, S, Paul, S E, Wendt, F R, Clarke, T-K, Lai, D, Reginsson, G W, Zhou, H, He, J, Baranger, D A A, Gudbjartsson, D F, Wedow, R, Adkins, D E, Adkins, A E, Alexander, J, Bacanu, S-A, Bigdeli, T B, Boden, J, Brown, S A, Bucholz, K K, Bybjerg-Grauholm, J, Corley, R P, Degenhardt, L, Dick, D M, Domingue, B W, Fox, L, Goate, A M, Gordon, S D, Hack, L M, Hancock, D B, Hartz, S M, Hickie, I B, Hougaard, D M, Krauter, K, Lind, P A, McClintick, J N, McQueen, M B, Meyers, J L, Montgomery, G W, Mors, O, Mortensen, P B, Nordentoft, M, Pearson, J F, Peterson, R E, Børglum, A D & Psychiatric Genomics Consortium Substance Use Disorders Workgroup 2020, ' A large-scale genome-wide association study meta-analysis of cannabis use disorder ', The Lancet Psychiatry, vol. 7, no. 12, pp. 1032-1045 . https://doi.org/10.1016/S2215-0366Test(20)30339-4
The Lancet Psychiatry, 7(12), 1032-1045. Elsevier Limited
The Lancet. Psychiatry
Johnson, E C, Demontis, D, Thorgeirsson, T E, Walters, R, Polimanti, R, Hatoum, A S, Sanchez-roige, S, Paul, S E, Wendt, F R, Clarke, T, Lai, D, Reginsson, G W, Zhou, H, He, J, Baranger, D A A, Gudbjartsson, D F, Wedow, R, Adkins, D, Adkins, A, Alexander, J, Bacanu, S, Bigdeli, T B, Boden, J, Brown, S A, Bucholz, K, Bybjerg-grauholm, J, Corley, R P, Degenhardt, L, Dick, D, Domingue, B, Fox, L, Goate, A M, Gordon, S, Hack, L, Hancock, D, Hartz, S, Hickie, I B, Hougaard, D M, Krauter, K, Lind, P, Mcclintick, J, Mcqueen, M, Meyers, J, Montgomery, G, Mors, O, Mortensen, P B, Nordentoft, M, Pearson, J F, Peterson, R, Reynolds, M, Rice, J, Runarsdottir, V, Saccone, N, Sherva, R, Silberg, J L, Tarter, R, Tyrfingsson, T, Wall, T, Webb, B, Werge, T, Wetherill, L, Wright, M J, Zellers, S, Adams, M J, Bierut, L, Boardman, J, Copeland, W, Farrer, L, Foroud, T M, Gillespie, N A, Grucza, R A, Harris, K M, Heath, A, Hesselbrock, V, Hewitt, J, Hopfer, C, Horwood, J, Iacono, W G, Johnson, E, Kendler, K, Kennedy, M, Kranzler, H, Madden, P A F, Maes, H, Maher, B, Martin, N G, Mcgue, M, Mcintosh, A M, Medland, S, Nelson, E C, Porjesz, B, Riley, B, Stallings, M, Vanyukov, M, Vrieze, S, Davis, L K, Bogdan, R, Gelernter, J, Edenberg, H, Stefansson, K, Børglum, A D, Agrawal, A, Walters, R, Polimanti, R, Johnson, E, Mcclintick, J, Hatoum, A, He, J, Wendt, F, Zhou, H, Adkins, A, Aliev, F, Bacanu, S, Batzler, A, Bertelsen, S, Biernacka, J, Bigdeli, T, Chen, L, Clarke, T, Chou, Y, Degenhardt, F, Docherty, A, Edwards, A, Fontanillas, P, Foo, J, Fox, L, Frank, J, Giegling, I, Gordon, S, Hack, L, Hartmann, A, Hartz, S, Heilmann-heimbach, S, Herms, S, Hodgkinson, C, Hoffman, P, Hottenga, J, Kennedy, M, Alanne-kinnunen, M, Konte, B, Lahti, J, Lahti-pulkkinen, M, Lai, D, Ligthart, L, Loukola, A, Maher, B, Mbarek, H, Mcintosh, A M, Mcqueen, M, Meyers, J, Milaneschi, Y, Palviainen, T, Pearson, J, Peterson, R, Ripatti, S, Ryu, E, Saccone, N, Salvatore, J, Sanchez-roige, S, Schwandt, M, Sherva, R, Streit, F, Strohmaier, J, Thomas, N, Wang, J, Webb, B, Wedow, R, Wetherill, L, Wills, A, Boardman, J, Chen, D, Choi, D, Copeland, W, Culverhouse, R, Dahmen, N, Degenhardt, L, Domingue, B, Elson, S, Frye, M, Gäbel, W, Hayward, C, Ising, M, Keyes, M, Kiefer, F, Kramer, J, Kuperman, S, Lucae, S, Lynskey, M, Maier, W, Mann, K, Männistö, S, Müller-myhsok, B, Murray, A, Nurnberger, J, Palotie, A, Preuss, U, Räikkönen, K, Reynolds, M, Ridinger, M, Scherbaum, N, Schuckit, M, Soyka, M, Treutlein, J, Witt, S, Wodarz, N, Zill, P, Adkins, D, Boden, J, Boomsma, D, Bierut, L, Brown, S, Bucholz, K, Cichon, S, Costello, E J, De Wit, H, Diazgranados, N, Dick, D, Eriksson, J, Farrer, L, Foroud, T, Gillespie, N, Goate, A, Goldman, D, Grucza, R, Hancock, D, Harris, K M, Heath, A, Hesselbrock, V, Hewitt, J, Hopfer, C, Horwood, J, Iacono, W, Johnson, E, Kaprio, J, Karpyak, V, Kendler, K, Kranzler, H, Krauter, K, Lichtenstein, P, Lind, P, Mcgue, M, Mackillop, J, Madden, P, Maes, H, Magnusson, P, Martin, N, Medland, S, Montgomery, G, Nelson, E, Nöthen, M, Palmer, A, Pederson, N, Penninx, B, Porjesz, B, Rice, J, Rietschel, M, Riley, B, Rose, R, Rujescu, D, Shen, P, Silberg, J, Stallings, M, Tarter, R, Vanyukov, M, Vrieze, S, Wall, T, Whitfield, J, Zhao, H, Neale, B, Gelernter, J, Edenberg, H & Agrawal, A 2020, ' A large-scale genome-wide association study meta-analysis of cannabis use disorder ', The Lancet Psychiatry, vol. 7, no. 12, pp. 1032-1045 . https://doi.org/10.1016/S2215-0366Test(20)30339-4
Johnson, E C, Demontis, D, Thorgeirsson, T E, Walters, R K, Polimanti, R, Hatoum, A S, Sanchez-Roige, S, Paul, S E, Wendt, F R, Clarke, T K, Lai, D, Reginsson, G W, Zhou, H, He, J, Baranger, D A A, Gudbjartsson, D F, Wedow, R, Adkins, D E, Adkins, A E, Alexander, J, Bacanu, S A, Bigdeli, T B, Boden, J, Brown, S A, Bucholz, K K, Bybjerg-Grauholm, J, Corley, R P, Degenhardt, L, Dick, D M, Domingue, B W, Fox, L, Goate, A M, Gordon, S D, Hack, L M, Hancock, D B, Hartz, S M, Hickie, I B, Hougaard, D M, Krauter, K, Lind, P A, McClintick, J N, McQueen, M B, Meyers, J L, Montgomery, G W, Mors, O, Mortensen, P B, Nordentoft, M, Pearson, J F, Peterson, R E, Werge, T & Psychiatric Genomics Consortium Substance Use Disorders Workgroup 2020, ' A large-scale genome-wide association study meta-analysis of cannabis use disorder ', The Lancet Psychiatry, vol. 7, no. 12, pp. 1032-1045 . https://doi.org/10.1016/S2215-0366Test(20)30339-4
Psychiatric Genomics Consortium Substance Use Disorders Workgroup 2020, ' A large-scale genome-wide association study meta-analysis of cannabis use disorder ', The Lancet Psychiatry, vol. 7, no. 12, pp. 1032-1045 . https://doi.org/10.1016/S2215-0366Test(20)30339-4
The Lancet Psychiatry

مصطلحات موضوعية: Risk, Marijuana Abuse, medicine.medical_specialty, Alcohol abuse, Disease, Polymorphism, Single Nucleotide, 3124 Neurology and psychiatry, 03 medical and health sciences, 0302 clinical medicine, SDG 3 - Good Health and Well-being, medicine, Humans, 030212 general & internal medicine, Psychiatry, Borderline personality disorder, Biological Psychiatry, business.industry, Articles, Mental illness, medicine.disease, Mental health, 030227 psychiatry, 3. Good health, Substance abuse, Psychiatry and Mental health, Translational science, business, Genome-Wide Association Study, Psychopathology

الوصف: Background: Variation in liability to cannabis use disorder has a strong genetic component (estimated twin and family heritability about 50–70%) and is associated with negative outcomes, including increased risk of psychopathology. The aim of the study was to conduct a large genome-wide association study (GWAS) to identify novel genetic variants associated with cannabis use disorder. Methods: To conduct this GWAS meta-analysis of cannabis use disorder and identify associations with genetic loci, we used samples from the Psychiatric Genomics Consortium Substance Use Disorders working group, iPSYCH, and deCODE (20 916 case samples, 363 116 control samples in total), contrasting cannabis use disorder cases with controls. To examine the genetic overlap between cannabis use disorder and 22 traits of interest (chosen because of previously published phenotypic correlations [eg, psychiatric disorders] or hypothesised associations [eg, chronotype] with cannabis use disorder), we used linkage disequilibrium score regression to calculate genetic correlations. Findings: We identified two genome-wide significant loci: a novel chromosome 7 locus (FOXP2, lead single-nucleotide polymorphism [SNP] rs7783012; odds ratio [OR] 1·11, 95% CI 1·07–1·15, p=1·84 × 10 −9) and the previously identified chromosome 8 locus (near CHRNA2 and EPHX2, lead SNP rs4732724; OR 0·89, 95% CI 0·86–0·93, p=6·46 × 10 −9). Cannabis use disorder and cannabis use were genetically correlated (r g 0·50, p=1·50 × 10 −21), but they showed significantly different genetic correlations with 12 of the 22 traits we tested, suggesting at least partially different genetic underpinnings of cannabis use and cannabis use disorder. Cannabis use disorder was positively genetically correlated with other psychopathology, including ADHD, major depression, and schizophrenia. Interpretation: These findings support the theory that cannabis use disorder has shared genetic liability with other psychopathology, and there is a distinction between genetic liability to cannabis use and cannabis use disorder. Funding: National Institute of Mental Health; National Institute on Alcohol Abuse and Alcoholism; National Institute on Drug Abuse; Center for Genomics and Personalized Medicine and the Centre for Integrative Sequencing; The European Commission, Horizon 2020; National Institute of Child Health and Human Development; Health Research Council of New Zealand; National Institute on Aging; Wellcome Trust Case Control Consortium; UK Research and Innovation Medical Research Council (UKRI MRC); The Brain & Behavior Research Foundation; National Institute on Deafness and Other Communication Disorders; Substance Abuse and Mental Health Services Administration (SAMHSA); National Institute of Biomedical Imaging and Bioengineering; National Health and Medical Research Council (NHMRC) Australia; Tobacco-Related Disease Research Program of the University of California; Families for Borderline Personality Disorder Research (Beth and Rob Elliott) 2018 NARSAD Young Investigator Grant; The National Child Health Research Foundation (Cure Kids); The Canterbury Medical Research Foundation; The New Zealand Lottery Grants Board; The University of Otago; The Carney Centre for Pharmacogenomics; The James Hume Bequest Fund; National Institutes of Health: Genes, Environment and Health Initiative; National Institutes of Health; National Cancer Institute; The William T Grant Foundation; Australian Research Council; The Virginia Tobacco Settlement Foundation; The VISN 1 and VISN 4 Mental Illness Research, Education, and Clinical Centers of the US Department of Veterans Affairs; The 5th Framework Programme (FP-5) GenomEUtwin Project; The Lundbeck Foundation; NIH-funded Shared Instrumentation Grant S10RR025141; Clinical Translational Sciences Award grants; National Institute of Neurological Disorders and Stroke; National Heart, Lung, and Blood Institute; National Institute of General Medical Sciences.

وصف الملف: application/pdf

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::b5e1394595d95a3f48eb1610651d6d82Test
https://doi.org/10.1016/s2215-0366Test(20)30339-4

المؤلفون: Susan F. Tapert, Michael C. Stallings, Evan A. Winiger, Christian J. Hopfer, Robin P. Corley, J. Megan Ross, John K. Hewitt, Jarrod M. Ellingson, Tamara L. Wall, Naomi P. Friedman, Sandra A. Brown

المصدر: Addiction

مصطلحات موضوعية: Adult, Marijuana Abuse, Adolescent, 030508 substance abuse, Medicine (miscellaneous), Neuropsychological Tests, Article, Young Adult, 03 medical and health sciences, Cognition, 0302 clinical medicine, Humans, Medicine, Prospective Studies, 030212 general & internal medicine, Cognitive skill, Effects of sleep deprivation on cognitive performance, Sibling, Cannabis, biology, business.industry, Siblings, Infant, Newborn, biology.organism_classification, Psychiatry and Mental health, Verbal memory, 0305 other medical science, business, Neurocognitive, Clinical psychology, Cohort study

الوصف: Aims To examine whether moderate adolescent cannabis use has neurocognitive effects that are unexplained by familial confounds, which prior family-controlled studies may not have identified. Design A quasi-experimental, sibling-comparison design was applied to a prospective, observational study of adolescents with moderate cannabis use. Participants were recruited from 2001 to 2006 (mean age = 17 years). A second wave of data was collected from 2008 to 2013 (mean age = 24 years). Setting Two US metropolitan communities. Participants A total of 1192 adolescents from 596 families participated in this study. Participants were primarily male (64%) and racially and ethnically diverse (non-Hispanic white = 45%). A sibling in each family was a clinical proband identified due to delinquent behaviors. Whereas prior family-controlled studies have used samples of primarily infrequent cannabis users (mean = 1-2 days/month), participants here endorsed levels of cannabis use comparable to findings from epidemiological cohort studies (mean = 7-9 days/month). Measurements Semi-structured clinical interviews assessed drug use, and a neuropsychological battery assessed cognitive abilities. Covariates included age at assessment, gender and alcohol use. Findings After correcting for multiple testing, a greater frequency and earlier onset of regular cannabis use were associated with poorer cognitive performance, specifically on tests of verbal memory. Further, after accounting for familial factors shared by siblings and alcohol use, poorer verbal memory performance was still associated with greater life-time frequency of cannabis use at wave 1 [b = -0.007 (-0.002, -0.012), adjusted P = 0.036]; earlier cannabis use at wave 2 [b = -0.12 (-0.05, -0.19), adjusted P = 0.006; b = -0.14 (-0.06, -0.23), adjusted P = 0.006]; and greater frequency of past 6 months use at wave 2 [b = -0.02 (-0.01, -0.03), adjusted P = 0.002; b = -0.02 (-0.01, -0.03), adjusted P = 0.008]. Conclusions Moderate adolescent cannabis use may have adverse effects on cognitive functioning, specifically verbal memory, that cannot be explained by familial factors.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3191281c47a51e35b604a5054cedc1b4Test
https://doi.org/10.1111/add.15207Test

المؤلفون: Eshim S. Jami, Anke R. Hammerschlag, Hill F. Ip, Andrea G. Allegrini, Beben Benyamin, Richard Border, Elizabeth W. Diemer, Chang Jiang, Ville Karhunen, Yi Lu, Qing Lu, Travis T. Mallard, Pashupati P. Mishra, Ilja M. Nolte, Teemu Palviainen, Roseann E. Peterson, Hannah M. Sallis, Andrey A. Shabalin, Ashley E. Tate, Elisabeth Thiering, Natàlia Vilor-Tejedor, Carol Wang, Ang Zhou, Daniel E. Adkins, Silvia Alemany, Helga Ask, Qi Chen, Robin P. Corley, Erik A. Ehli, Luke M. Evans, Alexandra Havdahl, Fiona A. Hagenbeek, Christian Hakulinen, Anjali K. Henders, Jouke Jan Hottenga, Tellervo Korhonen, Abdullah Mamun, Shelby Marrington, Alexander Neumann, Kaili Rimfeld, Fernando Rivadeneira, Judy L. Silberg, Catharina E. van Beijsterveldt, Eero Vuoksimaa, Alyce M. Whipp, Xiaoran Tong, Ole A. Andreassen, Dorret I. Boomsma, Sandra A. Brown, S. Alexandra Burt, William Copeland, Danielle M. Dick, K. Paige Harden, Kathleen Mullan Harris, Catharina A. Hartman, Joachim Heinrich, John K. Hewitt, Christian Hopfer, Elina Hypponen, Marjo-Riitta Jarvelin, Jaakko Kaprio, Liisa Keltikangas-Järvinen, Kelly L. Klump, Kenneth Krauter, Ralf Kuja-Halkola, Henrik Larsson, Terho Lehtimäki, Paul Lichtenstein, Sebastian Lundström, Hermine H. Maes, Per Magnus, Marcus R. Munafò, Jake M. Najman, Pål R. Njølstad, Albertine J. Oldehinkel, Craig E. Pennell, Robert Plomin, Ted Reichborn-Kjennerud, Chandra Reynolds, Richard J. Rose, Andrew Smolen, Harold Snieder, Michael Stallings, Marie Standl, Jordi Sunyer, Henning Tiemeier, Sally J. Wadsworth, Tamara L. Wall, Andrew J.O. Whitehouse, Gail M. Williams, Eivind Ystrøm, Michel G. Nivard, Meike Bartels, Christel M. Middeldorp

المساهمون: Jami, Eshim S, Hammerschlag, Anke R, Ip, Hill F, Allegrini, Andrea G, Benyamin, Beben, Zhou, Ang, Hypponen, Elina, Middeldorp, Christel M, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Mental Health, APH - Personalized Medicine, APH - Methodology, Life Course Epidemiology (LCE), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Tampere University, Clinical Medicine, Department of Clinical Chemistry, Institute for Molecular Medicine Finland, Genetic Epidemiology, Department of Psychology and Logopedics, Helsinki Inequality Initiative (INEQ), Psychosocial factors and health, Tellervo Korhonen / Principal Investigator, Cognitive and Brain Aging, Medicum, Child and Adolescent Psychiatry / Psychology, Clinical Genetics, Internal Medicine, Epidemiology

المصدر: J. Am. Acad. Child Adolesc. Psychiatry 61, 934-945 (2022)
Journal of the American Academy of Child and Adolescent Psychiatry
Journal of the American Academy of Child and Adolescent Psychiatry, 61(7), 934-945. Elsevier Limited
J Am Acad Child Adolesc Psychiatry
Journal of the American Academy of Child and Adolescent Psychiatry, 61(7), 934-945. ELSEVIER SCIENCE INC
Jami, E S, Hammerschlag, A R, Ip, H F, Allegrini, A G, Benyamin, B, Border, R, Diemer, E W, Jiang, C, Karhunen, V, Lu, Y, Lu, Q, Mallard, T T, Mishra, P P, Nolte, I M, Palviainen, T, Peterson, R E, Sallis, H M, Shabalin, A A, Tate, A E, Thiering, E, Vilor-Tejedor, N, Wang, C, Zhou, A, Adkins, D E, Alemany, S, Ask, H, Chen, Q, Corley, R P, Ehli, E A, Evans, L M, Havdahl, A, Hagenbeek, F A, Hakulinen, C, Henders, A K, Hottenga, J J, Korhonen, T, Mamun, A, Marrington, S, Neumann, A, Rimfeld, K, Rivadeneira, F, Silberg, J L, van Beijsterveldt, C E, Vuoksimaa, E, Whipp, A M, Tong, X, Andreassen, O A, Boomsma, D I, Brown, S A, Burt, S A, Copeland, W, Dick, D M, Harden, K P, Harris, K M, Hartman, C A, Heinrich, J, Hewitt, J K, Hopfer, C, Hypponen, E, Jarvelin, M R, Kaprio, J, Keltikangas-Järvinen, L, Klump, K L, Krauter, K, Kuja-Halkola, R, Larsson, H, Lehtimäki, T, Lichtenstein, P, Lundström, S, Maes, H H, Magnus, P, Munafò, M R, Najman, J M, Njølstad, P R, Oldehinkel, A J, Pennell, C E, Plomin, R, Reichborn-Kjennerud, T, Reynolds, C, Rose, R J, Smolen, A, Snieder, H, Stallings, M, Standl, M, Sunyer, J, Tiemeier, H, Wadsworth, S J, Wall, T L, Whitehouse, A J O, Williams, G M, Ystrøm, E, Nivard, M G, Bartels, M & Middeldorp, C M 2022, ' Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms ', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 61, no. 7, pp. 934-945 . https://doi.org/10.1016/j.jaac.2021.11.035Test
Journal of the American Academy of Child and Adolescent Psychiatry, 61(7), 934-945. Elsevier Ltd.
Jami, E S, Hammerschlag, A R, Ip, H F, Allegrini, A G, Benyamin, B, Border, R, Diemer, E W, Jiang, C, Karhunen, V, Lu, Y, Lu, Q, Mallard, T T, Mishra, P P, Nolte, I M, Palviainen, T, Peterson, R E, Sallis, H M, Shabalin, A A, Tate, A E, Thiering, E, Vilor-Tejedor, N, Wang, C, Zhou, A, Adkins, D E, Alemany, S, Ask, H, Chen, Q, Corley, R P, Ehli, E A, Evans, L M, Havdahl, A, Hagenbeek, F A, Hakulinen, C, Henders, A K, Hottenga, J J, Korhonen, T, Mamun, A, Marrington, S, Neumann, A, Rimfeld, K, Rivadeneira, F, Silberg, J L, van Beijsterveldt, C E, Vuoksimaa, E, Whipp, A M, Tong, X, Andreassen, O A, Boomsma, D I, Brown, S A, Burt, S A, Copeland, W, Dick, D M, Harden, K P, Harris, K M, Hartman, C A, Heinrich, J, Hewitt, J K, Hopfer, C, Hypponen, E, Jarvelin, M-R, Kaprio, J, Keltikangas-Järvinen, L, Klump, K L, Krauter, K, Kuja-Halkola, R, Larsson, H, Lehtimäki, T, Lichtenstein, P, Lundström, S, Maes, H H, Magnus, P, Munafò, M R, Najman, J M, Njølstad, P R, Oldehinkel, A J, Pennell, C E, Plomin, R, Reichborn-Kjennerud, T, Reynolds, C, Rose, R J, Smolen, A, Snieder, H, Stallings, M, Standl, M, Sunyer, J, Tiemeier, H, Wadsworth, S J, Wall, T L, Whitehouse, A J O, Williams, G M, Ystrøm, E, Nivard, M G, Bartels, M & Middeldorp, C M 2022, ' Genome-wide Association Meta-analysis of Childhood and Adolescent Internalizing Symptoms ', Journal of the American Academy of Child and Adolescent Psychiatry, vol. 61, no. 7, pp. 934-945 . https://doi.org/10.1016/j.jaac.2021.11.035Test

مصطلحات موضوعية: Adult, SDG 16 - Peace, Bipolar Disorder, genetic epidemiology, Adolescent, 515 Psychology, education, QUESTIONNAIRE, CHILDREN, BEHAVIORAL-PROBLEMS, Adolescents, Polymorphism, Single Nucleotide, 3124 Neurology and psychiatry, Angoixa, repeated measures, SDG 3 - Good Health and Well-being, Sleep Initiation and Maintenance Disorders, MENTAL-DISORDERS, Developmental and Educational Psychology, Humans, Depressió psíquica, Autistic Disorder, Child, MAJOR DEPRESSIVE DISORDER, RISK, Anxiety, Depression, Genetic Epidemiology, Molecular Genetics, Repeated Measures, HERITABILITY, Loneliness, SDG 16 - Peace, Justice and Strong Institutions, PSYCHOPATHOLOGY, anxiety, Justice and Strong Institutions, PREVALENCE, Aggression, Genòmica, Psychiatry and Mental health, Attention Deficit Disorder with Hyperactivity, Child, Preschool, depression, molecular genetics, Schizophrenia, 3111 Biomedicine, Infants, Genètica, Genome-Wide Association Study

الوصف: Objective: To investigate the genetic architecture of internalizing symptoms in childhood and adolescence. Method: In 22 cohorts, multiple univariate genome-wide association studies (GWASs) were performed using repeated assessments of internalizing symptoms, in a total of 64,561 children and adolescents between 3 and 18 years of age. Results were aggregated in meta-analyses that accounted for sample overlap, first using all available data, and then using subsets of measurements grouped by rater, age, and instrument. Results: The meta-analysis of overall internalizing symptoms (INToverall) detected no genome-wide significant hits and showed low single nucleotide polymorphism (SNP) heritability (1.66%, 95% CI = 0.84-2.48%, neffective = 132,260). Stratified analyses indicated rater-based heterogeneity in genetic effects, with self-reported internalizing symptoms showing the highest heritability (5.63%, 95% CI = 3.08%-8.18%). The contribution of additive genetic effects on internalizing symptoms appeared to be stable over age, with overlapping estimates of SNP heritability from early childhood to adolescence. Genetic correlations were observed with adult anxiety, depression, and the well-being spectrum (|rg| > 0.70), as well as with insomnia, loneliness, attention-deficit/hyperactivity disorder, autism, and childhood aggression (range |rg| = 0.42-0.60), whereas there were no robust associations with schizophrenia, bipolar disorder, obsessive-compulsive disorder, or anorexia nervosa. Conclusion: Genetic correlations indicate that childhood and adolescent internalizing symptoms share substantial genetic vulnerabilities with adult internalizing disorders and other childhood psychiatric traits, which could partially explain both the persistence of internalizing symptoms over time and the high comorbidity among childhood psychiatric traits. Reducing phenotypic heterogeneity in childhood samples will be key in paving the way to future GWAS success. Dr. Border has received support from the National Institutes of Health (NIH; MH100141 and MH016880 ). Dr. Peterson has received support from NIH (K01MH113848) and the Brain & Behavior Research Foundation Young Investigator Grant (28632). Drs. Sallis and Munafò have served as members of the MRC Integrative Epidemiology Unit at the University of Bristol (MC_UU_00011/7). Dr. Shabalin has received support from a NARSAD Young Investigator Award. Dr. Vilor-Tejedor has received support from a post-doctoral grant, Juan de la Cierva Programme (FJC2018-038085-I), Ministerio de Ciencia, Innovación y Universidades – Spanish State Research Agency. Her research has received additional support of “la Caixa” Foundation (LCF/PR/GN17/10300004) and the Health Department of the Catalan Government (Health Research and Innovation Strategic Plan (PERIS) 2016-2020 grant# SLT002/16/00201). She has acknowledged the support of the Spanish Ministry of Science, Innovation and Universities to the EMBL partnership, the Centro de Excelencia Severo Ochoa, and the CERCA Programme/Generalitat de Catalunya. Dr. Alemany has received support from a Juan de la Cierva – Incorporación Postdoctoral Contract from Ministerio de Economía, Industria y Competitividad (IJCI-2017-34068). Dr. Corley has received support from NIH (DA011015, AG046938, and DA035804). Dr. Evans has received support from NIH (MH100141, DA044283, and AG046938). Dr. Havdahl has received support from the South-Eastern Norway Regional Health Authority (2018059) at Nic Waals Institute, Lovisenberg Diaconal Hospital. Dr. Rimfeld has received support from a Sir Henry Wellcome Postdoctoral Fellowship. Dr. Andreassen has served as a consultant to HealthLytix and has received funding from the Research Council of Norway (223273 and 273291) and KG Jebsen Stiftelsen. Dr. Boomsma has received support from the Royal Netherlands Academy of Science Professor Award (PAH/5535). Dr. Brown has received support from NIH (DA035804). Dr. Copeland has received support from NIH (MH117559 and HD093651). Dr. Dick has received support from a mid-career award NIH K02 AA018755, NIH R01 AA015416 (Finnish Twin Study), P50 AA022537 (Alcohol Research Center), R25 AA027402 (VCU GREAT), and U10 AA008401 (COGA) from the National Institute on Alcohol Abuse and Alcoholism. Drs. Hewitt, Krauter, Smolen, and Stallings have received support from NIH (DA011015 and DA035804). Dr. Hopfer has received support from NIH (DA042755, DA035804, and DA032555). Dr. Kaprio has received support from the Academy of Finland (grants 308248 and 312073). Dr. Larsson has served as a speaker for Evolan Pharma and Shire/Takeda and has received research grants from Shire/Takeda, all outside the submitted work. Dr. Lichtenstein has received support from the Swedish Research Council for Health, Working Life and Welfare (project 2012-1678) and the Swedish Research Council (2016-1989). Dr. Lundström has received support from the Swedish Research Council ( 2017-02552 ). Dr. Magnus has received support from the Research Council of Norway through its Centers of Excellence scheme, project no 262700. Dr. Njølstad has received support from the European Research Council (AdG #293574). Stiftelsen Kristian Gerhard Jebsen has received support from the Research Council of Norway (FRIPRO 240413), the Western Norway Regional Health Authority (Strategic Fund “Personalized Medicine for Children and Adults”) and the Novo Nordisk Foundation (54741). Dr. Plomin has received support from a MRC Professorship award (G19/2). Dr. Reichborn-Kjennerud has received support from the Research Council of Norway grant 274611 . Drs. Reynolds and Wadsworth have received support from NIH (AG046938). Dr. Rose has received support from a NIH Research Scientist Award (AA-000145). Dr. Wall has received support from NIH (DA03580 and DA021905). Dr. Whitehouse has received support from an Investigator Grant from the National Health and Medical Research Council. Dr. Ystrøm has received support from the Research Council of Norway (262177 and 288083). Dr. Nivard has received support from ZonMW (849200011), the Netherlands Organisation for Health Research and Development (531003014 937), a Jacobs Foundation Research Fellowship, and a VENI grant awarded by NWO (VI.Veni.191G.030). Dr. Bartels has received support from an ERC Consolidator Grant (WELL-BEING 771057). Ms. Hagenbeek and Mr. Ip have received support from the Aggression in Children: Unraveling gene-environment interplay to inform Treatment and Intervention strategies project (ACTION). ACTION received funding from the European Union Seventh Framework Program (FP7/2007-2013) under grant agreement no 602768

وصف الملف: application/pdf; fulltext

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::47ed516833bce7047e1b95cdb8366f86Test
https://hdl.handle.net/11541.2/28861Test

المؤلفون: Tamara L. Wall, Susan E. Luczak, Melike Sirlanci, I. Gary Rosen

المصدر: Alcohol

مصطلحات موضوعية: Male, Health (social science), Calibration (statistics), Population, Alcohol, Biosensing Techniques, Population based, Toxicology, Biochemistry, Article, Wearable Electronic Devices, Young Adult, 03 medical and health sciences, Behavioral Neuroscience, chemistry.chemical_compound, 0302 clinical medicine, Statistics, Humans, education, Transdermal, education.field_of_study, Models, Statistical, Ethanol, General Medicine, 030227 psychiatry, Breath Tests, Neurology, chemistry, Population model, Population data, Female, 030217 neurology & neurosurgery, Breath alcohol concentration

الوصف: Alcohol biosensor devices have been developed to unobtrusively measure transdermal alcohol concentration (TAC), the amount of ethanol diffusing through the skin, in nearly continuous fashion in naturalistic settings. Because TAC data are affected by physiological and environmental factors that vary across individuals and drinking episodes, there is not an elementary formula to convert TAC into easily interpretable metrics such as blood and breath alcohol concentrations (BAC/BrAC). In our prior work, we addressed this conversion problem in a deterministic way by developing physics/physiological-based models to convert TAC to estimated BrAC (eBrAC), in which the model parameter values were individually determined for each person wearing a specific transdermal sensor using simultaneously collected TAC (via a biosensor) and BrAC (via a breath analyzer) during a calibration episode. We found these individualized parameter values produced relatively good eBrAC curves for subsequent drinking episodes, but our results also indicated the models were not fully capturing the dynamics of the system and variations across drinking episodes. Here, we report on a novel mathematical framework to improve our ability to model eBrAC from TAC data that uses aggregate population data instead of individualized calibration data to determine model parameter values via a random diffusion equation. We first provide the theoretical mathematical basis for our approach, and then test the efficacy of this method using datasets of contemporaneous BrAC/TAC measurements obtained by a) a single subject during multiple drinking episodes and b) multiple subjects during single drinking episodes. For each dataset, we used a set of drinking episodes to construct the population model, and then ran the model with another set of randomly selected test episodes. We compared raw TAC data to model-simulated TAC curve, breath analyzer BrAC data to model eBrAC curve with 75% credible bands, episode summary scores of peak BrAC, times of peak BrAC, and area under the drinking curve also with 75% credible intervals, and report the percent of the raw BrAC captured within the eBrAC curve credible bands. We also display results when stratifying the data based on the relationship between the raw BrAC and TAC data. Results indicate the population-based model is promising, with better fit within a single participant when stratifying episodes. This study provides initial proof-of-concept for constructing, fitting, and using a population-based model to obtain estimates and error bands for BrAC from TAC. The advancements in this study, including new applications of math, the development of a population-based model with error bars, and the production of corresponding MATLAB codes, represent a major step forward in our ability to produce quantitatively- and temporally-accurate estimates of BrAC from TAC biosensor data.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2f2e8eab99cb26f5190c2c8512d73923Test
https://doi.org/10.1016/j.alcohol.2018.09.005Test

المؤلفون: Sandra A. Brown, Jason D. Boardman, Scott A. Funkhouser, Luke M. Evans, Tamara L. Wall, John K. Hewitt, Chandra A. Reynolds, Christian J. Hopfer, Matthew C. Keller, Michael C. Stallings

مصطلحات موضوعية: Generalized anxiety disorder, business.industry, medicine.medical_treatment, Genome-wide association study, Single-nucleotide polymorphism, medicine.disease, Genetic architecture, Medicine, Major depressive disorder, SNP, Anxiety, Smoking cessation, medicine.symptom, business, Clinical psychology

الوصف: The genetic architecture of numerous smoking behaviors is highly polygenic, but these genetic effects are heterogeneous and depend on moderating factors. Here, we used common SNPs from the UK Biobank to investigate heterogeneous genetic effects for smoking heaviness using cigarettes per day (CPD) records, smoking initiation (SI), and smoking cessation (SC). We assessed heterogeneous effects across levels of sex, age of smoking initiation, major depressive disorder (MDD) DSM-V-like diagnosis, generalized anxiety disorder (GAD) DSM-V-like diagnosis, and whether an individual has seen a psychiatrist for nerves, anxiety, tension, or depression. We observed suggestive evidence of heterogeneous genetic effects for CPD and SC, moderated by MDD and GAD, respectively [ (SE = 0.15) between MDD cases and controls, and (SE = 0.28) between GAD cases and controls, p < 0.05]. We detected 5 SNPs with genome-wide significant evidence of heterogeneous effects moderated by either MDD or GAD (p-value < 5×10-8) for CPD and SC. We also observed strong evidence for heterogeneous genetic effects for SI between sexes (between-sex , SE = 0.02). While we detected no individual SNPs that were moderated by sex at genome-wide significance (all p-value > 5×10-8), we observed evidence of novel genome-wide significant SI-SNP associations using sex-stratified GWAS; six loci were discovered in either men or women separately that were not identified in a previous smoking meta-analysis that had a 6-fold larger, sex-combined sample. Furthermore, using several independent testing samples, there was suggestive evidence that the prediction ability of a polygenic risk score (PRS) for smoking initiation improved through the utilization of sex-specific SNP effects. This work suggests that a more nuanced approach to GWAS analyses is warranted, as potential heterogeneous effects can complicate variant discovery and polygenic risk score accuracy.Author SummarySmoking imposes a heavy health burden and is highly polygenic in architecture. Consistent with most complex traits, many causal loci have yet to be identified, even when using the largest available samples. One possible reason for the difficulty in inferring genetic variants associated with such complex traits is that common genetic variants possess context-dependent (or heterogeneous) effects. Utilizing the UK Biobank, we find evidence for heterogeneous SNP effects on smoking initiation, heaviness, and cessation among psychiatric disorder cases and controls and between sexes. Failure to model such heterogeneity (when accounting for sample size) resulted in lower independent sample predictive ability. This work encourages a more nuanced approach to GWAS and polygenic risk prediction. The assumption that all genetic effects are homogeneous limits our understanding of complex traits when heterogeneous effects are present.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::23a79df5008409c5364327fae7ee4568Test
https://doi.org/10.1101/2021.08.08.21261764Test

المؤلفون: Aesoon Park, Tamara L. Wall, Michelle J. Zaso, Patricia A. Goodhines

المصدر: Alcohol Alcohol

مصطلحات موضوعية: 030508 substance abuse, Original Manuscript, Alcohol use disorder, 03 medical and health sciences, Sex Factors, 0302 clinical medicine, Asian People, Genotype, medicine, Humans, Ethanol metabolism, Allele, Alleles, Genetic Association Studies, ALDH2, Ethanol, business.industry, Aldehyde Dehydrogenase, Mitochondrial, Age Factors, Alcohol Dehydrogenase, ADH1B, General Medicine, Moderation, medicine.disease, Alcoholism, Meta-analysis, 0305 other medical science, business, 030217 neurology & neurosurgery, Demography

الوصف: AIMS: The current meta-analysis tested independent and composite associations of three commonly studied alcohol metabolism alleles with alcohol use disorder (AUD) within East Asians as well as characterized potential moderating factors in these associations. METHODS: For meta-analysis, 32 articles were selected that investigated ALDH2 (n = 17,755), ADH1B (n = 13,591) and ADH1C (n = 4,093) associations with AUD in East Asians. RESULTS AND CONCLUSIONS: All three variants were associated with AUD across allelic and genotypic models: ALDH2, ORs = 0.25, P < 0.001; ADH1B, ORs = 0.22–0.49, P < 0.001; ADH1C, ORs = 0.26–0.46, P < 0.001. Composite analyses suggested genetic associations did not differ across ALDH2*2 and ADH1B*2, correcting for multiple comparisons. Moderation analyses suggested ADH1B was more strongly associated with AUD among samples with cases recruited from treatment than the community. Also, strength of ALDH2 and/or ADH1B associations varied with mean age and proportion of men in cases and controls. Findings support medium to large and unique associations of ALDH2, ADH1B, and ADH1C with AUD in East Asians. Results also identified novel methodological and sample characteristics that may modulate strength of these associations.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::99939367fce77bcab02afc800715b1b6Test
https://doi.org/10.1093/alcalc/agz011Test