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3 results on '"Geisinger-Regeneron DiscovEHR Collaboration"'

1. Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program

Author

Klarin, Derek, Damrauer, Scott M, Cho, Kelly, Sun, Yan V, Teslovich, Tanya M, Honerlaw, Jacqueline, Gagnon, David R, DuVall, Scott L, Li, Jin, Peloso, Gina M, Chaffin, Mark, Small, Aeron M, Huang, Jie, Tang, Hua, Lynch, Julie A, Ho, Yuk-Lam, Liu, Dajiang J, Emdin, Connor A, Li, Alexander H, Huffman, Jennifer E, Lee, Jennifer S, Natarajan, Pradeep, Chowdhury, Rajiv, Saleheen, Danish, Vujkovic, Marijana, Baras, Aris, Pyarajan, Saiju, Di Angelantonio, Emanuele, Neale, Benjamin M, Naheed, Aliya, Khera, Amit V, Danesh, John, Chang, Kyong-Mi, Abecasis, Gonçalo, Willer, Cristen, Dewey, Frederick E, Carey, David J, Global Lipids Genetics Consortium, Myocardial Infarction Genetics (MIGen) Consortium, Geisinger-Regeneron DiscovEHR Collaboration, VA Million Veteran Program, Concato, John, Gaziano, J Michael, O'Donnell, Christopher J, Tsao, Philip S, Kathiresan, Sekar, Rader, Daniel J, Wilson, Peter WF, Assimes, Themistocles L, Gagnon, David R [0000-0002-6367-3179], Chaffin, Mark [0000-0002-1234-5562], Emdin, Connor A [0000-0002-2385-8259], Huffman, Jennifer E [0000-0002-9672-2491], Vujkovic, Marijana [0000-0003-4924-5714], Neale, Benjamin M [0000-0003-1513-6077], Willer, Cristen [0000-0001-5645-4966], Kathiresan, Sekar [0000-0002-6724-032X], Assimes, Themistocles L [0000-0003-2349-0009], and Apollo - University of Cambridge Repository

Subjects
Male, Genotype, Black People, Hispanic or Latino, Middle Aged, Lipid Metabolism, Lipids, Polymorphism, Single Nucleotide, White People, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Ethnicity, Humans, Female, Aged, Genome-Wide Association Study, Veterans
Abstract

The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).

Published
2018

2. Genome-wide association analyses for lung function and chronic obstructive pulmonary disease identify new loci and potential druggable targets

Author

Wain, LV, Shrine, N, Artigas, MS, Erzurumluoglu, AM, Noyvert, B, Bossini-Castillo, L, Obeidat, M, Henry, AP, Portelli, MA, Hall, RJ, Billington, CK, Rimington, TL, Fenech, AG, John, C, Blake, T, Jackson, VE, Allen, RJ, Prins, BP, Understanding Society Scientific Group, Campbell, A, Porteous, DJ, Jarvelin, M-R, Wielscher, M, James, AL, Hui, J, Wareham, NJ, Zhao, JH, Wilson, JF, Joshi, PK, Stubbe, B, Rawal, R, Schulz, H, Imboden, M, Probst-Hensch, NM, Karrasch, S, Gieger, C, Deary, IJ, Harris, SE, Marten, J, Rudan, I, Enroth, S, Gyllensten, U, Kerr, SM, Polasek, O, Kähönen, M, Surakka, I, Vitart, V, Hayward, C, Lehtimäki, T, Raitakari, OT, Evans, DM, Henderson, AJ, Pennell, CE, Wang, CA, Sly, PD, Wan, ES, Busch, R, Hobbs, BD, Litonjua, AA, Sparrow, DW, Gulsvik, A, Bakke, PS, Crapo, JD, Beaty, TH, Hansel, NN, Mathias, RA, Ruczinski, I, Barnes, KC, Bossé, Y, Joubert, P, Van Den Berge, M, Brandsma, C-A, Paré, PD, Sin, DD, Nickle, DC, Hao, K, Gottesman, O, Dewey, FE, Bruse, SE, Carey, DJ, Kirchner, HL, Geisinger-Regeneron DiscovEHR Collaboration, Jonsson, S, Thorleifsson, G, Jonsdottir, I, Gislason, T, Stefansson, K, Schurmann, C, Nadkarni, G, Bottinger, EP, Loos, RJF, Walters, RG, Chen, Z, Millwood, IY, Vaucher, J, Kurmi, OP, Li, L, Hansell, AL, Brightling, C, Zeggini, E, Cho, MH, Silverman, EK, Sayers, I, Trynka, G, Morris, AP, Strachan, DP, Hall, IP, and Tobin, MD

Subjects
Adult, Aged, 80 and over, Male, Middle Aged, Polymorphism, Single Nucleotide, Asthma, respiratory tract diseases, 3. Good health, Epigenesis, Genetic, Pulmonary Disease, Chronic Obstructive, Genetic Loci, Risk Factors, Humans, Female, Genetic Predisposition to Disease, Lung, Alleles, Aged, Genome-Wide Association Study
Abstract

Chronic obstructive pulmonary disease (COPD) is characterized by reduced lung function and is the third leading cause of death globally. Through genome-wide association discovery in 48,943 individuals, selected from extremes of the lung function distribution in UK Biobank, and follow-up in 95,375 individuals, we increased the yield of independent signals for lung function from 54 to 97. A genetic risk score was associated with COPD susceptibility (odds ratio per 1 s.d. of the risk score (∼6 alleles) (95% confidence interval) = 1.24 (1.20-1.27), P = 5.05 × 10‾⁴⁹), and we observed a 3.7-fold difference in COPD risk between individuals in the highest and lowest genetic risk score deciles in UK Biobank. The 97 signals show enrichment in genes for development, elastic fibers and epigenetic regulation pathways. We highlight targets for drugs and compounds in development for COPD and asthma (genes in the inositol phosphate metabolism pathway and CHRM3) and describe targets for potential drug repositioning from other clinical indications.

3. Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program

Author

Klarin, Derek, Damrauer, Scott M, Cho, Kelly, Sun, Yan V, Teslovich, Tanya M, Honerlaw, Jacqueline, Gagnon, David R, DuVall, Scott L, Li, Jin, Peloso, Gina M, Chaffin, Mark, Small, Aeron M, Huang, Jie, Tang, Hua, Lynch, Julie A, Ho, Yuk-Lam, Liu, Dajiang J, Emdin, Connor A, Li, Alexander H, Huffman, Jennifer E, Lee, Jennifer S, Natarajan, Pradeep, Chowdhury, Rajiv, Saleheen, Danish, Vujkovic, Marijana, Baras, Aris, Pyarajan, Saiju, Di Angelantonio, Emanuele, Neale, Benjamin M, Naheed, Aliya, Khera, Amit V, Danesh, John, Chang, Kyong-Mi, Abecasis, Gonçalo, Willer, Cristen, Dewey, Frederick E, Carey, David J, Global Lipids Genetics Consortium, Myocardial Infarction Genetics (MIGen) Consortium, Geisinger-Regeneron DiscovEHR Collaboration, VA Million Veteran Program, Concato, John, Gaziano, J Michael, O'Donnell, Christopher J, Tsao, Philip S, Kathiresan, Sekar, Rader, Daniel J, Wilson, Peter WF, and Assimes, Themistocles L

Subjects
Male, Genotype, Black People, Hispanic or Latino, Middle Aged, 16. Peace & justice, Lipid Metabolism, Lipids, Polymorphism, Single Nucleotide, White People, 3. Good health, Diabetes Mellitus, Type 2, Cardiovascular Diseases, Ethnicity, Humans, Female, Aged, Genome-Wide Association Study, Veterans
Abstract

The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n > 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).

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