المؤلفون: Puya Gharahkhani, Eric Jorgenson, Pirro Hysi, Anthony P. Khawaja, Sarah Pendergrass, Xikun Han, Jue Sheng Ong, Alex W. Hewitt, Ayellet V. Segrè, John M. Rouhana, Andrew R. Hamel, Robert P. Igo, Helene Choquet, Ayub Qassim, Navya S. Josyula, Jessica N. Cooke Bailey, Pieter W. M. Bonnemaijer, Adriana Iglesias, Owen M. Siggs, Terri L. Young, Veronique Vitart, Alberta A. H. J. Thiadens, Juha Karjalainen, Steffen Uebe, Ronald B. Melles, K. Saidas Nair, Robert Luben, Mark Simcoe, Nishani Amersinghe, Angela J. Cree, Rene Hohn, Alicia Poplawski, Li Jia Chen, Shi-Song Rong, Tin Aung, Eranga Nishanthie Vithana, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, and Me Research Team, Gen Tamiya, Yukihiro Shiga, Masayuki Yamamoto, Toru Nakazawa, Hannah Currant, Ewan Birney, Xin Wang, Adam Auton, Michelle K. Lupton, Nicholas G. Martin, Adeyinka Ashaye, Olusola Olawoye, Susan E. Williams, Stephen Akafo, Michele Ramsay, Kazuki Hashimoto, Yoichiro Kamatani, Masato Akiyama, Yukihide Momozawa, Paul J. Foster, Peng T. Khaw, James E. Morgan, Nicholas G. Strouthidis, Peter Kraft, Jae H. Kang, Chi Pui Pang, Francesca Pasutto, Paul Mitchell, Andrew J. Lotery, Aarno Palotie, Cornelia van Duijn, Jonathan L. Haines, Chris Hammond, Louis R. Pasquale, Caroline C. W. Klaver, Michael Hauser, Chiea Chuen Khor, David A. Mackey, Michiaki Kubo, Ching-Yu Cheng, Jamie E. Craig, Stuart MacGregor, Janey L. Wiggs

المصدر: Nature Communications, Vol 12, Iss 1, Pp 1-16 (2021)

مصطلحات موضوعية: Science

الوصف: Primary open-angle glaucoma (POAG) is highly heritable, yet not well understood from a genetic perspective. Here, the authors perform a meta-analysis of genome-wide association studies in 34,179 POAG cases, identifying 44 previously unreported risk loci and mapping effects across multiple ethnicities.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2041-1723Test

الوصول الحر: https://doaj.org/article/ea46188f0f2c4f0cae58f959caf971a2Test

المؤلفون: Olivia J. Veatch, Christopher R. Bauer, Brendan T. Keenan, Navya S. Josyula, Diego R. Mazzotti, Kanika Bagai, Beth A. Malow, Janet D. Robishaw, Allan I. Pack, Sarah A. Pendergrass

المصدر: BMC Medical Genomics, Vol 13, Iss 1, Pp 1-14 (2020)

مصطلحات موضوعية: Sleep disorders, Obstructive sleep apnea, Genetics, Pleiotropy, Electronic health records, Internal medicine, RC31-1245, QH426-470

الوصف: Abstract Background Obstructive sleep apnea (OSA) is defined by frequent episodes of reduced or complete cessation of airflow during sleep and is linked to negative health outcomes. Understanding the genetic factors influencing expression of OSA may lead to new treatment strategies. Electronic health records (EHRs) can be leveraged to both validate previously reported OSA-associated genomic variation and detect novel relationships between these variants and comorbidities. Methods We identified candidate single nucleotide polymorphisms (SNPs) via systematic literature review of existing research. Using datasets available at Geisinger (n = 39,407) and Vanderbilt University Medical Center (n = 24,084), we evaluated associations between 40 previously implicated SNPs and OSA diagnosis, defined using clinical codes. We also evaluated associations between these SNPs and OSA severity measures obtained from sleep reports at Geisinger (n = 6571). Finally, we used a phenome-wide association study approach to help reveal pleiotropic genetic effects between OSA candidate SNPs and other clinical codes and laboratory values available in the EHR. Results Most previously reported OSA candidate SNPs showed minimal to no evidence for associations with OSA diagnosis or severity in the EHR-derived datasets. Three SNPs in LEPR, MMP-9, and GABBR1 validated for an association with OSA diagnosis in European Americans; the SNP in GABBR1 was associated following meta-analysis of results from both clinical populations. The GABBR1 and LEPR SNPs, and one additional SNP, were associated with OSA severity measures in European Americans from Geisinger. Three additional candidate OSA SNPs were not associated with OSA-related traits but instead with hyperlipidemia and autoimmune diseases of the thyroid. Conclusions To our knowledge, this is one of the largest candidate gene studies and one of the first phenome-wide association studies of OSA genomic variation. Results validate genetic associates with OSA in the LEPR, MMP-9 and GABBR1 genes, but suggest that the majority of previously identified genetic associations with OSA may be false positives. Phenome-wide analyses provide evidence of mediated pleiotropy. Future well-powered genome-wide association analyses of OSA risk and severity across populations with diverse ancestral backgrounds are needed. The comprehensive nature of the analyses represents a platform for informing future work focused on understanding how genetic data can be useful to informing treatment of OSA and related comorbidities.

وصف الملف: electronic resource

العلاقة: http://link.springer.com/article/10.1186/s12920-020-00755-4Test; https://doaj.org/toc/1755-8794Test

الوصول الحر: https://doaj.org/article/07db0b9375dd45d294cb4940b819edcaTest

المؤلفون: Laney K, Jones, Alanna, Kulchak Rahm, Kandamurugu, Manickam, Loren, Butry, Amanda, Lazzeri, Timothy, Corcoran, Daniel, Komar, Navya S, Josyula, Sarah A, Pendergrass, Amy C, Sturm, Michael F, Murray

المصدر: Circulation. Genomic and precision medicine. 11(8)

مصطلحات موضوعية: Adult, Aged, 80 and over, Male, Anticholesteremic Agents, Middle Aged, Patient Acceptance of Health Care, Cohort Studies, Hyperlipoproteinemia Type II, Receptors, LDL, Apolipoprotein B-100, Secondary Prevention, Humans, Female, Perception, Genetic Testing, Attitude to Health, Aged

الوصف: The MyCode Community Health Initiative (MyCode) is returning actionable results from whole exome sequencing. Familial hypercholesterolemia (FH) is an inherited condition characterized by premature cardiovascular disease.We used multiple methods to assess care in 28 MyCode participants who received FH results. Chart reviews were conducted on 23 individuals in the sample and 7 individuals participated semistructured interviews.Chart reviews for 23 individuals with a Geisinger primary care provider found that 4 individuals (17% of 23) were at LDL-C (low-density lipoprotein cholesterol) goal (of either LDL-C100 mg/dL for primary prevention and LDL-C70 mg/dL for secondary prevention) and 17 individuals (74% of 23) were prescribed lipid-lowering therapy before genetic result disclosure. After disclosure of the genetic test result, 5 individuals (22% of 23) met their LDL-C goal and 18 individuals (78% of 23) were prescribed lipid-lowering therapy. Follow-up care about this result was not documented for 4 individuals (17% of 23). Changes to intensity of medication management were made for 8 individuals (47% of 17 individuals previously prescribed lipid-lowering therapy). Interviewed individuals (n=7) were not surprised by their result as all knew they had high cholesterol; however, individuals did not seem to discern FH as a separate condition from their high cholesterol.Among individuals receiving genetic diagnosis of FH,25% had no changes to lipid-lowering therapy, despite not being at LDL-C goal and learning their high cholesterol is related to a genetic condition requiring more aggressive treatment. Individuals and clinicians may have an inadequate understanding of FH as a distinct condition requiring enhanced medical management.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::7e8589283cf15b042754ffab18e94688Test
https://pubmed.ncbi.nlm.nih.gov/30354341Test