المؤلفون: Engelen, Marscha M., Franken, Marie-Christine J. P., Stipdonk, Lottie W., Horton, Sarah E., Jackson, Victoria E., Reilly, Sheena, Morgan, Angela T., Fisher, Simon E., van Dulmen, Sandra, Eising, Else

مصطلحات موضوعية: Speech pathology, Speech production, Mental health services

الوصف: Purpose: Stuttering is a speech condition that can have a major impact on a person’s quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life. Method: The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden. Results: We identified a high- ( n = 230) and a low-burden subgroup ( n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, ...

العلاقة: https://dx.doi.org/10.23641/asha.25582980Test; https://dx.doi.org/10.1044/2024_jslhr-23-00562Test

الإتاحة: https://doi.org/10.23641/asha.25582980.v110.23641/asha.2558298010.1044/2024_jslhr-23-00562Test
https://asha.figshare.com/articles/online_resource/Stuttering_burden_and_psychosocial_impact_Engelen_et_al_2024_/25582980/1Test

المؤلفون: Braat, Sabine, Fielding, Katherine L., Han, Jiru, Jackson, Victoria E., Zaloumis, Sophie, Xu, Jessica Xu Hui, Moir-Meyer, Gemma, Blaauwendraad, Sophia M., Jaddoe, Vincent W.V., Gaillard, Romy, Parkin, Patricia C., Borkhoff, Cornelia M., Keown-Stoneman, Charles D.G., Birken, Catherine S., Maguire, Jonathon L., Bahlo, Melanie, Davidson, Eliza M., Pasricha, Sant Rayn

المصدر: Braat , S , Fielding , K L , Genes & Health Research Team , Han , J , Jackson , V E , Zaloumis , S , Xu , J X H , Moir-Meyer , G , Blaauwendraad , S M , Jaddoe , V W V , Gaillard , R , Parkin , P C , Borkhoff , C M , Keown-Stoneman , C D G , Birken , C S , Maguire , J L , Bahlo , M , Davidson , E M & Pasricha , S R 2024 , ' Haemoglobin thresholds to define ....

مصطلحات موضوعية: /dk/atira/pure/sustainabledevelopmentgoals/good_health_and_well_being, name=SDG 3 - Good Health and Well-being

الوصف: Background: Detection of anaemia is crucial for clinical medicine and public health. Current WHO anaemia definitions are based on statistical thresholds (fifth centiles) set more than 50 years ago. We sought to establish evidence for the statistical haemoglobin thresholds for anaemia that can be applied globally and inform WHO and clinical guidelines. Methods: In this analysis we identified international data sources from populations in the USA, England, Australia, China, the Netherlands, Canada, Ecuador, and Bangladesh with sufficient clinical and laboratory information collected between 1998 and 2020 to obtain a healthy reference sample. Individuals with clinical or biochemical evidence of a condition that could reduce haemoglobin concentrations were excluded. We estimated haemoglobin thresholds (ie, 5th centiles) for children aged 6–23 months, 24–59 months, 5–11 years, and 12–17 years, and adults aged 18–65 years (including during pregnancy) for individual datasets and pooled across data sources. We also collated findings from three large-scale genetic studies to summarise genetic variants affecting haemoglobin concentrations in different ancestral populations. Findings: We identified eight data sources comprising 18 individual datasets that were eligible for inclusion in the analysis. In pooled analyses, the haemoglobin fifth centile was 104·4 g/L (90% CI 103·5–105·3) in 924 children aged 6–23 months, 110·2 g/L (109·5–110·9) in 1874 children aged 24–59 months, and 114·4 g/L (113·6–115·2) in 1839 children aged 5–11 years. Values diverged by sex in adolescents and adults. In pooled analyses, the fifth centile was 122·2 g/L (90% CI 121·3–123·1) in 1741 female adolescents aged 12–17 years and 128·2 g/L (126·4–130·0) in 1103 male adolescents aged 12–17 years. In pooled analyses of adults aged 18–65 years, the fifth centile was 119·7 g/L (90% CI 119·1–120·3) in 3640 non-pregnant females and 134·9 g/L (134·2–135·6) in 2377 males. Fifth centiles in pregnancy were 110·3 g/L (90% CI 109·5–111·0) in the first trimester ...

وصف الملف: application/pdf

العلاقة: https://pure.eur.nl/en/publications/16345a00-ecc5-4c3c-805a-43c08a17941bTest

الإتاحة: https://doi.org/10.1016/S2352-3026Test(24)00030-9
https://pure.eur.nl/en/publications/16345a00-ecc5-4c3c-805a-43c08a17941bTest
https://pure.eur.nl/ws/files/141423220/1-s2.0-S2352302624000309-main.pdfTest
http://www.scopus.com/inward/record.url?scp=85187694617&partnerID=8YFLogxKTest

المؤلفون: Engelen, Marscha M., Franken, Marie-Christine J. P., Stipdonk, Lottie W., Horton, Sarah E., Jackson, Victoria E., Reilly, Sheena, Morgan, Angela T., Fisher, Simon E., van Dulmen, Sandra, Eising, Else

المصدر: Journal of Speech, Language and Hearing Research. 67(5):1385-1399

مصطلحات موضوعية: Människan i vården, The Human Perspective in Care

الوصف: PURPOSE: Stuttering is a speech condition that can have a major impact on a person's quality of life. This descriptive study aimed to identify subgroups of people who stutter (PWS) based on stuttering burden and to investigate differences between these subgroups on psychosocial aspects of life.METHOD: The study included 618 adult participants who stutter. They completed a detailed survey examining stuttering symptomatology, impact of stuttering on anxiety, education and employment, experience of stuttering, and levels of depression, anxiety, and stress. A two-step cluster analytic procedure was performed to identify subgroups of PWS, based on self-report of stuttering frequency, severity, affect, and anxiety, four measures that together inform about stuttering burden.RESULTS: We identified a high- (n = 230) and a low-burden subgroup (n = 372). The high-burden subgroup reported a significantly higher impact of stuttering on education and employment, and higher levels of general depression, anxiety, stress, and overall impact of stuttering. These participants also reported that they trialed more different stuttering therapies than those with lower burden.CONCLUSIONS: Our results emphasize the need to be attentive to the diverse experiences and needs of PWS, rather than treating them as a homogeneous group. Our findings also stress the importance of personalized therapeutic strategies for individuals with stuttering, considering all aspects that could influence their stuttering burden. People with high-burden stuttering might, for example, have a higher need for psychological therapy to reduce stuttering-related anxiety. People with less emotional reactions but severe speech distortions may also have a moderate to high burden, but they may have a higher need for speech techniques to communicate with more ease. Future research should give more insights into the therapeutic needs of people highly burdened by their stuttering.SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.25582980Test.

وصف الملف: print

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:hb:diva-31898Test

المؤلفون: Erzurumluoglu, A. Mesut, Liu, Mengzhen, Jackson, Victoria E., Barnes, Daniel R., Datta, Gargi, Melbourne, Carl A., Young, Robin, Batini, Chiara, Surendran, Praveen, Jiang, Tao, Adnan, Sheikh Daud, Afaq, Saima, Agrawal, Arpana, Altmaier, Elisabeth, Antoniou, Antonis C., Asselbergs, Folkert W., Baumbach, Clemens, Bierut, Laura, Bertelsen, Sarah, Boehnke, Michael, Bots, Michiel L, Brazel, David M, Chambers, John C, Chang-Claude, Jenny, Chen, Chu, Corley, Janie, Chou, Yi-Ling, David, Sean P, de Boer, Rudolf A, de Leeuw, Christiaan A, Dennis, Joe G, Dominiczak, Anna F, Dunning, Alison M, Easton, Douglas F, Eaton, Charles, Elliott, Paul, Evangelou, Evangelos, Faul, Jessica D, Foroud, Tatiana, Goate, Alison, Gong, Jian, Grabe, Hans J, Haessler, Jeff, Haiman, Christopher, Hallmans, Göran, 1947, Hammerschlag, Anke R, Harris, Sarah E, Hattersley, Andrew, Heath, Andrew, Hsu, Chris, Iacono, William G, Kanoni, Stavroula, Kapoor, Manav, Kaprio, Jaakko, Kardia, Sharon L, Karpe, Fredrik, Kontto, Jukka, Kooner, Jaspal S, Kooperberg, Charles, Kuulasmaa, Kari, Laakso, Markku, Lai, Dongbing, Langenberg, Claudia, Le, Nhung, Lettre, Guillaume, Loukola, Anu, Luan, Jian'an, Madden, Pamela A F, Mangino, Massimo, Marioni, Riccardo E, Marouli, Eirini, Marten, Jonathan, Martin, Nicholas G, McGue, Matt, Michailidou, Kyriaki, Mihailov, Evelin, Moayyeri, Alireza, Moitry, Marie, Müller-Nurasyid, Martina, Naheed, Aliya, Nauck, Matthias, Neville, Matthew J, Nielsen, Sune Fallgaard, North, Kari, Perola, Markus, Pharoah, Paul D P, Pistis, Giorgio, Polderman, Tinca J, Posthuma, Danielle, Poulter, Neil, Qaiser, Beenish, Rasheed, Asif, Reiner, Alex, Renstrom, Frida, Rice, John, Rohde, Rebecca, Rolandsson, Olov, Samani, Nilesh J, Samuel, Maria, Schlessinger, David, Scholte, Steven H, Scott, Robert A, Sever, Peter, Shao, Yaming, Shrine, Nick, Smith, Jennifer A, Starr, John M, Stirrups, Kathleen, Stram, Danielle, Stringham, Heather M, Tachmazidou, Ioanna, Tardif, Jean-Claude, Thompson, Deborah J, Tindle, Hilary A, Tragante, Vinicius, Trompet, Stella, Turcot, Valerie, Tyrrell, Jessica, Vaartjes, Ilonca, van der Leij, Andries R, van der Meer, Peter, Varga, Tibor V, Verweij, Niek, Völzke, Henry, Wareham, Nicholas J, Warren, Helen R, Weir, David R, Weiss, Stefan, Wetherill, Leah, Yaghootkar, Hanieh, Yavas, Ersin, Jiang, Yu, Chen, Fang, Zhan, Xiaowei, Zhang, Weihua, Zhao, Wei, Zhou, Kaixin, Amouyel, Philippe, Blankenberg, Stefan, Caulfield, Mark J, Chowdhury, Rajiv, Cucca, Francesco, Deary, Ian J, Deloukas, Panos, Di Angelantonio, Emanuele, Ferrario, Marco, Ferrières, Jean, Franks, Paul W, Frayling, Tim M, Frossard, Philippe, Hall, Ian P, Hayward, Caroline, Jansson, Jan-Håkan, Jukema, J Wouter, Kee, Frank, Männistö, Satu, Metspalu, Andres, Munroe, Patricia B, Nordestgaard, Børge Grønne, Palmer, Colin N A, Salomaa, Veikko, Sattar, Naveed, Spector, Timothy, Strachan, David Peter, van der Harst, Pim, Zeggini, Eleftheria, Saleheen, Danish, Butterworth, Adam S, Wain, Louise V, Abecasis, Goncalo R, Danesh, John, Tobin, Martin D, Vrieze, Scott, Liu, Dajiang J, Howson, Joanna M M

المصدر: Molecular Psychiatry. 25(10):2392-2409

الوصف: Smoking is a major heritable and modifiable risk factor for many diseases, including cancer, common respiratory disorders and cardiovascular diseases. Fourteen genetic loci have previously been associated with smoking behaviour-related traits. We tested up to 235,116 single nucleotide variants (SNVs) on the exome-array for association with smoking initiation, cigarettes per day, pack-years, and smoking cessation in a fixed effects meta-analysis of up to 61 studies (up to 346,813 participants). In a subset of 112,811 participants, a further one million SNVs were also genotyped and tested for association with the four smoking behaviour traits. SNV-trait associations with P < 5 × 10-8 in either analysis were taken forward for replication in up to 275,596 independent participants from UK Biobank. Lastly, a meta-analysis of the discovery and replication studies was performed. Sixteen SNVs were associated with at least one of the smoking behaviour traits (P < 5 × 10-8) in the discovery samples. Ten novel SNVs, including rs12616219 near TMEM182, were followed-up and five of them (rs462779 in REV3L, rs12780116 in CNNM2, rs1190736 in GPR101, rs11539157 in PJA1, and rs12616219 near TMEM182) replicated at a Bonferroni significance threshold (P < 4.5 × 10-3) with consistent direction of effect. A further 35 SNVs were associated with smoking behaviour traits in the discovery plus replication meta-analysis (up to 622,409 participants) including a rare SNV, rs150493199, in CCDC141 and two low-frequency SNVs in CEP350 and HDGFRP2. Functional follow-up implied that decreased expression of REV3L may lower the probability of smoking initiation. The novel loci will facilitate understanding the genetic aetiology of smoking behaviour and may lead to the identification of potential drug targets for smoking prevention and/or cessation.

وصف الملف: electronic

الوصول الحر: https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-156372Test
https://doi.org/10.1038/s41380-018-0313-0Test
https://umu.diva-portal.org/smash/get/diva2:1288340/FULLTEXT02.pdfTest

المؤلفون: Morgan, Angela T, Scerri, Thomas S, Vogel, Adam P, Reid, Christopher A, Quach, Mara, Jackson, Victoria E, McKenzie, Chaseley, Burrows, Emma L, Bennett, Mark F, Turner, Samantha J, Reilly, Sheena, Horton, Sarah E, Block, Susan, Kefalianos, Elaina, Frigerio-Domingues, Carlos

مصطلحات موضوعية: Proteomics and metabolomics, Biomedical and clinical sciences, Health sciences, Psychology, PPID gene, brain MRI, chaperone, cyclophilin-40, stuttering

الوصف: Stuttering is a common speech disorder that interrupts speech fluency and tends to cluster in families. Typically, stuttering is characterized by speech sounds, words or syllables which may be repeated or prolonged and speech that may be further interrupted by hesitations or 'blocks'. Rare variants in a small number of genes encoding lysosomal pathway proteins have been linked to stuttering. We studied a large four-generation family in which persistent stuttering was inherited in an autosomal dominant manner with disruption of the cortico-basal-ganglia-thalamo-cortical network found on imaging. Exome sequencing of three affected family members revealed the PPID c.808C>T (p.Pro270Ser) variant that segregated with stuttering in the family. We generated a Ppid p.Pro270Ser knock-in mouse model and performed ex vivo imaging to assess for brain changes. Diffusion-weighted MRI in the mouse revealed significant microstructural changes in the left corticospinal tract, as previously implicated in stuttering. Quantitative susceptibility mapping also detected changes in cortico-striatal-thalamo-cortical loop tissue composition, consistent with findings in affected family members. This is the first report to implicate a chaperone protein in the pathogenesis of stuttering. The humanized Ppid murine model recapitulates network findings observed in affected family members. ; Full Text

العلاقة: Brain; Morgan, AT; Scerri, TS; Vogel, AP; Reid, CA; Quach, M; Jackson, VE; McKenzie, C; Burrows, EL; Bennett, MF; Turner, SJ; Reilly, S; Horton, SE; Block, S; Kefalianos, E; Frigerio-Domingues, C; Sainz, E; Rigbye, KA; Featherby, TJ; Richards, KL; Kueh, A; Herold, MJ; Corbett, MA; Gecz, J; Helbig, I; Thompson-Lake, DGY; Liégeois, FJ; Morell, RJ; Hung, A; Drayna, D; Scheffer, IE; Wright, DK; Bahlo, M; Hildebrand, MS, Stuttering associated with a pathogenic variant in the chaperone protein cyclophilin 40., Brain, 2023, 146 (12), pp. 5086-5097; http://hdl.handle.net/10072/427505Test

الإتاحة: https://doi.org/10.1093/brain/awad314Test
http://hdl.handle.net/10072/427505Test

المؤلفون: Garnish, Sarah E., Martin, Katherine R., Kauppi, Maria, Jackson, Victoria E., Ambrose, Rebecca, Eng, Vik Ven, Chiou, Shene, Meng, Yanxiang, Frank, Daniel, Tovey Crutchfield, Emma C., Patel, Komal M., Jacobsen, Annette V., Atkin-Smith, Georgia K., Di Rago, Ladina, Doerflinger, Marcel, Horne, Christopher R., Hall, Cathrine, Young, Samuel N., Cook, Matthew, Athanasopoulos, Vicki, Vinuesa, Carola G., Lawlor, Kate E., Wicks, Ian P., Ebert, Gregor, Ng, Ashley P., Slade, Charlotte A., Pearson, Jaclyn S., Samson, André L., Silke, John, Murphy, James M., Hildebrand, Joanne M.

المساهمون: Department of Health | National Health and Medical Research Council

المصدر: Nature Communications ; volume 14, issue 1 ; ISSN 2041-1723

مصطلحات موضوعية: General Physics and Astronomy, General Biochemistry, Genetics and Molecular Biology, General Chemistry, Multidisciplinary

الوصف: Across the globe, 2-3% of humans carry the p.Ser132Pro single nucleotide polymorphism in MLKL , the terminal effector protein of the inflammatory form of programmed cell death, necroptosis. Here we show that this substitution confers a gain in necroptotic function in human cells, with more rapid accumulation of activated MLKL S132P in biological membranes and MLKL S132P overriding pharmacological and endogenous inhibition of MLKL. In mouse cells, the equivalent Mlkl S131P mutation confers a gene dosage dependent reduction in sensitivity to TNF-induced necroptosis in both hematopoietic and non-hematopoietic cells, but enhanced sensitivity to IFN-β induced death in non-hematopoietic cells. In vivo, Mlkl S131P homozygosity reduces the capacity to clear Salmonella from major organs and retards recovery of hematopoietic stem cells. Thus, by dysregulating necroptosis, the S131P substitution impairs the return to homeostasis after systemic challenge. Present day carriers of the MLKL S132P polymorphism may be the key to understanding how MLKL and necroptosis modulate the progression of complex polygenic human disease.

الإتاحة: https://doi.org/10.1038/s41467-023-41724-6Test
https://www.nature.com/articles/s41467-023-41724-6.pdfTest
https://www.nature.com/articles/s41467-023-41724-6Test

المؤلفون: Kaspi, Antony, Hildebrand, Michael S., Jackson, Victoria E., Braden, Ruth, van Reyk, Olivia, Howell, Tegan, Debono, Simone, Lauretta, Mariana, Morison, Lottie, Coleman, Matthew J., Webster, Richard, Coman, David, Goel, Himanshu, Wallis, Mathew, Dabscheck, Gabriel, Downie, Lilian, Baker, Emma K., Parry-Fielder, Bronwyn, Ballard, Kirrie, Harrold, Eva, Ziegenfusz, Shaun, Bennett, Mark F., Robertson, Erandee, Wang, Longfei, Boys, Amber, Fisher, Simon E., Amor, David J., Scheffer, Ingrid E., Bahlo, Melanie, Morgan, Angela T.

المصدر: Molecular Psychiatry ; volume 28, issue 4, page 1664-1666 ; ISSN 1359-4184 1476-5578

مصطلحات موضوعية: Cellular and Molecular Neuroscience, Psychiatry and Mental health, Molecular Biology

الإتاحة: https://doi.org/10.1038/s41380-022-01879-yTest
https://www.nature.com/articles/s41380-022-01879-y.pdfTest
https://www.nature.com/articles/s41380-022-01879-yTest

المؤلفون: Wyss, Annah B, Sofer, Tamar, Lee, Mi Kyeong, Terzikhan, Natalie, Nguyen, Jennifer N, Lahousse, Lies, Latourelle, Jeanne C, Smith, Albert Vernon, Bartz, Traci M, Feitosa, Mary F, Gao, Wei, Ahluwalia, Tarunveer S, Tang, Wenbo, Oldmeadow, Christopher, Duan, Qing, de Jong, Kim, Wojczynski, Mary K, Wang, Xin-Qun, Noordam, Raymond, Hartwig, Fernando Pires, Jackson, Victoria E, Wang, Tianyuan, Obeidat, Ma'en, Hobbs, Brian D, Huan, Tianxiao, Gui, Hongsheng, Parker, Margaret M, Hu, Donglei, Mogil, Lauren S, Kichaev, Gleb, Jin, Jianping, Graff, Mariaelisa, Harris, Tamara B, Kalhan, Ravi, Heckbert, Susan R, Paternoster, Lavinia, Burkart, Kristin M, Liu, Yongmei, Holliday, Elizabeth G, Wilson, James G, Vonk, Judith M, Sanders, Jason L, Barr, R Graham, de Mutsert, Renée, Menezes, Ana Maria Baptista, Adams, Hieab HH, van den Berge, Maarten, Joehanes, Roby, Levin, Albert M, Liberto, Jennifer, Launer, Lenore J, Morrison, Alanna C, Sitlani, Colleen M, Celedón, Juan C, Kritchevsky, Stephen B, Scott, Rodney J, Christensen, Kaare, Rotter, Jerome I, Bonten, Tobias N, Wehrmeister, Fernando César, Bossé, Yohan, Xiao, Shujie, Oh, Sam, Franceschini, Nora, Brody, Jennifer A, Kaplan, Robert C, Lohman, Kurt, McEvoy, Mark, Province, Michael A, Rosendaal, Frits R, Taylor, Kent D, Nickle, David C, Williams, L Keoki, Burchard, Esteban G, Wheeler, Heather E, Sin, Don D, Gudnason, Vilmundur, North, Kari E, Fornage, Myriam, Psaty, Bruce M, Myers, Richard H, O'Connor, George, Hansen, Torben, Laurie, Cathy C, Cassano, Patricia A, Sung, Joohon, Kim, Woo Jin, Attia, John R, Lange, Leslie, Boezen, H Marike, Thyagarajan, Bharat, Rich, Stephen S, Mook-Kanamori, Dennis O, Horta, Bernardo Lessa, Uitterlinden, André G, Im, Hae Kyung, Cho, Michael H, Brusselle, Guy G, Gharib, Sina A

المصدر: Nature communications. 9(1)

مصطلحات موضوعية: Lung, Humans, Lung Diseases, Pulmonary Disease, Chronic Obstructive, Genetic Predisposition to Disease, Vital Capacity, Forced Expiratory Volume, Regression Analysis, Sample Size, Smoking, Genomics, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Quantitative Trait Loci, African Continental Ancestry Group, Asian Americans, European Continental Ancestry Group, Hispanic Americans, Female, Male, Genome-Wide Association Study, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive

الوصف: Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/4cx2v3pkTest

المؤلفون: Hobbs, Brian D, de Jong, Kim, Lamontagne, Maxime, Bossé, Yohan, Shrine, Nick, Artigas, María Soler, Wain, Louise V, Hall, Ian P, Jackson, Victoria E, Wyss, Annah B, London, Stephanie J, North, Kari E, Franceschini, Nora, Strachan, David P, Beaty, Terri H, Hokanson, John E, Crapo, James D, Castaldi, Peter J, Chase, Robert P, Bartz, Traci M, Heckbert, Susan R, Psaty, Bruce M, Gharib, Sina A, Zanen, Pieter, Lammers, Jan W, Oudkerk, Matthijs, Groen, HJ, Locantore, Nicholas, Tal-Singer, Ruth, Rennard, Stephen I, Vestbo, Jørgen, Timens, Wim, Paré, Peter D, Latourelle, Jeanne C, Dupuis, Josée, O'Connor, George T, Wilk, Jemma B, Kim, Woo Jin, Lee, Mi Kyeong, Oh, Yeon-Mok, Vonk, Judith M, de Koning, Harry J, Leng, Shuguang, Belinsky, Steven A, Tesfaigzi, Yohannes, Manichaikul, Ani, Wang, Xin-Qun, Rich, Stephen S, Barr, R Graham, Sparrow, David, Litonjua, Augusto A, Bakke, Per, Gulsvik, Amund, Lahousse, Lies, Brusselle, Guy G, Stricker, Bruno H, Uitterlinden, André G, Ampleford, Elizabeth J, Bleecker, Eugene R, Woodruff, Prescott G, Meyers, Deborah A, Qiao, Dandi, Lomas, David A, Yim, Jae-Joon, Kim, Deog Kyeom, Hawrylkiewicz, Iwona, Sliwinski, Pawel, Hardin, Megan, Fingerlin, Tasha E, Schwartz, David A, Postma, Dirkje S, MacNee, William, Tobin, Martin D, Silverman, Edwin K, Boezen, H Marike, Cho, Michael H

المصدر: Nature Genetics. 49(3)

مصطلحات موضوعية: Biological Sciences, Genetics, Chronic Obstructive Pulmonary Disease, Lung, Human Genome, Clinical Research, Aetiology, 2.1 Biological and endogenous factors, Respiratory, Adult, Aged, Aged, 80 and over, Alleles, Asthma, Female, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Pulmonary Disease, Chronic Obstructive, Pulmonary Fibrosis, Risk Factors, Smoking, COPDGene Investigators, ECLIPSE Investigators, LifeLines Investigators, SPIROMICS Research Group, International COPD Genetics Network Investigators, UK BiLEVE Investigators, International COPD Genetics Consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology

الوصف: Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality worldwide. We performed a genetic association study in 15,256 cases and 47,936 controls, with replication of select top results (P < 5 × 10-6) in 9,498 cases and 9,748 controls. In the combined meta-analysis, we identified 22 loci associated at genome-wide significance, including 13 new associations with COPD. Nine of these 13 loci have been associated with lung function in general population samples, while 4 (EEFSEC, DSP, MTCL1, and SFTPD) are new. We noted two loci shared with pulmonary fibrosis (FAM13A and DSP) but that had opposite risk alleles for COPD. None of our loci overlapped with genome-wide associations for asthma, although one locus has been implicated in joint susceptibility to asthma and obesity. We also identified genetic correlation between COPD and asthma. Our findings highlight new loci associated with COPD, demonstrate the importance of specific loci associated with lung function to COPD, and identify potential regions of genetic overlap between COPD and other respiratory diseases.

وصف الملف: application/pdf

الوصول الحر: https://escholarship.org/uc/item/9dn8h0n3Test

المؤلفون: Shrine, Nick, Guyatt, Anna L, Erzurumluoglu, A Mesut, Jackson, Victoria E., Hobbs, Brian D, Melbourne, Carl A, Batini, Chiara, Fawcett, Katherine A, Song, Kijoung, Sakornsakolpat, Phuwanat, Li, Xingnan, Boxall, Ruth, Reeve, Nicola F, Obeidat, Ma'en, Zhao, Jing Hua, Wielscher, Matthias, Weiss, Stefan, Kentistou, Katherine A, Cook, James P, Sun, Benjamin B, Zhou, Jian, Hui, Jennie, Karrasch, Stefan, Imboden, Medea, Harris, Sarah E, Marten, Jonathan, Enroth, Stefan, Kerr, Shona M, Surakka, Ida, Vitart, Veronique, Lehtimäki, Terho, Allen, Richard J, Bakke, Per S, Beaty, Terri H, Bleecker, Eugene R, Bossé, Yohan, Brandsma, Corry-Anke, Chen, Zhengming, Crapo, James D, Danesh, John, DeMeo, Dawn L, Dudbridge, Frank, Ewert, Ralf, Gieger, Christian, Gulsvik, Amund, Hansell, Anna L, Hao, Ke, Hoffman, Joshua D, Hokanson, John E, Homuth, Georg, Joshi, Peter K., Joubert, Philippe, Langenberg, Claudia, Li, Xuan, Li, Liming, Lin, Kuang, Lind, Lars, Locantore, Nicholas, Luan, Jian'an, Mahajan, Anubha, Maranville, Joseph C., Murray, Alison D., Nickle, David C., Packer, Richard, Parker, Margaret M., Paynton, Megan L., Porteous, David J., Prokopenko, Dmitry, Qiao, Dandi, Rawal, Rajesh, Runz, Heiko, Sayers, Ian, Smith, Blair H, Sin, Don D., Artigas, María Soler, Sparrow, David, Tal-Singer, Ruth, Timmers, Paul R.H.J., Van den Berge, Maarten, Whittaker, John C., Woodruff, Prescott G., Yerges-Armstrong, Laura M., Troyanskaya, Olga G., Raitakari, Olli T., Kähönen, Mika, Polasek, Ozren, Gyllensten, Ulf B., Rudan, Igor, Deary, Ian J., Probst-Hensch, Nicole M., Schulz, Holger, James, Alan L., Wilson, James F., Stubbe, Beate, Zeggini, Eleftheria, Järvelin, Marjo-Riitta, Wareham, Nick, Silverman, Edwin K., Hayward, Caroline, Morris, Andrew P., Butterworth, Adam S., Scott, Robert A., Walters, Robin G, Meyers, Deborah A., Cho, Michael H., Strachan, David P., Hall, Ian P., Tobin, Martin D., Wain, Louise V.

المصدر: Shrine , N , Guyatt , A L , Erzurumluoglu , A M , Jackson , V E , Hobbs , B D , Melbourne , C A , Batini , C , Fawcett , K A , Song , K , Sakornsakolpat , P , Li , X , Boxall , R , Reeve , N F , Obeidat , M , Zhao , J H , Wielscher , M , Understanding Society Scientific Group , Weiss , S , Kentistou , K A , Cook , J P , Sun , B B , Zhou , J ....

الوصف: Correction to: Nature Genetics https://doi.org/10.1038/s41588-018-0321-7Test, published online 25 February 2019.

العلاقة: https://discovery.dundee.ac.uk/en/publications/6bb400f7-ac03-47b3-9d00-5bb5eda9dbd0Test

الإتاحة: https://doi.org/10.1038/s41588-024-01752-4Test
https://discovery.dundee.ac.uk/en/publications/6bb400f7-ac03-47b3-9d00-5bb5eda9dbd0Test