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

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 ; Concato, John ; Gaziano, J Michael ; O'Donnell, Christopher J ; Tsao, Philip S ; Kathiresan, Sekar ; Rader, Daniel J ; Wilson, Peter W F ; Assimes, Themistocles L

Nature genetics, 2018-11, Vol.50 (11), p.1514-1523 [Periódico revisado por pares]

United States: Nature Publishing Group

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Título:
Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program
Autor: 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 ; Concato, John ; Gaziano, J Michael ; O'Donnell, Christopher J ; Tsao, Philip S ; Kathiresan, Sekar ; Rader, Daniel J ; Wilson, Peter W F ; Assimes, Themistocles L
Assuntos: Abdomen ; Abdominal aortic aneurysm ; African Continental Ancestry Group - genetics ; African Continental Ancestry Group - statistics & numerical data ; Aged ; Analysis ; Aneurysm ; Angioplasty ; Aorta ; Aortic aneurysm ; Blood ; Blood lipids ; Cardiovascular disease ; Cardiovascular Diseases - blood ; Cardiovascular Diseases - ethnology ; Cardiovascular Diseases - genetics ; Cholesterol ; Consortia ; Coronary heart disease ; Data processing ; Diabetes ; Diabetes mellitus ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - blood ; Diabetes Mellitus, Type 2 - ethnology ; Diabetes Mellitus, Type 2 - genetics ; Electronic health records ; Electronic medical records ; Electronic records ; Ethnic Groups - genetics ; Ethnic Groups - statistics & numerical data ; European Continental Ancestry Group - genetics ; European Continental Ancestry Group - statistics & numerical data ; Female ; Gene loci ; Genes ; Genetic aspects ; Genetic diversity ; Genetic research ; Genetic variation ; Genetics ; Genome-Wide Association Study ; Genomes ; Genomics ; Genotype ; Health aspects ; Heart diseases ; Hispanic Americans - genetics ; Hispanic Americans - statistics & numerical data ; Hispanic people ; Humans ; Laboratories ; Lipid Metabolism - genetics ; Lipids ; Lipids - blood ; Male ; Medical records ; Medical schools ; Meta-analysis ; Middle Aged ; Military personnel ; Mutation ; Phenotypes ; Polymorphism, Single Nucleotide ; Principal components analysis ; Quality control ; R&D ; Research & development ; Studies ; Triglycerides ; Type 2 diabetes ; Veterans ; Veterans - statistics & numerical data ; Wellness programs
É parte de: Nature genetics, 2018-11, Vol.50 (11), p.1514-1523
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
content type line 23
Concept and design: D.K., T.L.A., S.M.D., K.C., K-M. C, P.S.T, S.K., D.J.R., P.W.W., J.C., J.M.G.
Acquisition, analysis, or interpretation of data: D.K., S.M.D, Y.V.S, K.C., Y.V.S, T.M.T., J.H., D.R.G, S.L.D., Jin L., G.P., M.C., A.M.S, Jie H., H.T., J.L., Y.H., D.L., C.A.E., A.H.L., J.H., J.S.L., R.C., P.N., D.S., M.V., A.B., S.P., E.D., B.M.N., A.N., A.V.K., J.D., K-M.C., G.A., C.W., F.E.D., D.J.C.
Drafting of the manuscript: D.K., T.L.A.
Critical revision of the manuscript for important intellectual content: S.M.D., Y.V.S, K.C., P.N, C.W., J.L., F.E.D., S.L.D., K-M. C, C.J.O., P.S.T, S.K., D.J.R, P.W.W
These authors jointly supervised work
Administrative, technical, or material support: D.K., Y.V.S, K.C., J.H., D.R.G, S.L.D, J.L., Y.H., J.C., J.M.G, C.J.O, P.S.T, P.W.W.
Author Contributions
Descrição: 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).
Editor: United States: Nature Publishing Group
Idioma: Inglês

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

United States: Nature Publishing Group

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