Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.
Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.
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DOI：
10.1038/s41588-018-0222-9
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发表时间：
2018-11
期刊：
影响因子：
30.8
通讯作者：
Assimes TL
中科院分区：
文献类型：
--
作者：
Klarin D;Damrauer SM;Cho K;Sun YV;Teslovich TM;Honerlaw J;Gagnon DR;DuVall SL;Li J;Peloso GM;Chaffin M;Small AM;Huang J;Tang H;Lynch JA;Ho YL;Liu DJ;Emdin CA;Li AH;Huffman JE;Lee JS;Natarajan P;Chowdhury R;Saleheen D;Vujkovic M;Baras A;Pyarajan S;Di Angelantonio E;Neale BM;Naheed A;Khera AV;Danesh J;Chang KM;Abecasis G;Willer C;Dewey FE;Carey DJ;Global Lipids Genetics Consortium;Myocardial Infarction Genetics (MIGen) Consortium;Geisinger-Regeneron DiscovEHR Collaboration;VA Million Veteran Program;Concato J;Gaziano JM;O'Donnell CJ;Tsao PS;Kathiresan S;Rader DJ;Wilson PWF;Assimes TL
百万退伍军人计划(MVP)成立于2011年，是一项全国性的研究计划，旨在确定基因变异如何影响美国退伍军人的健康。我们使用定制的生物库阵列对312,571名MVP参与者进行了基因分型，并将基因数据与从电子健康记录中提取的实验室和临床表型联系起来，跟踪调查的中位数为10.0年。在297,626名至少有1次血脂测量的退伍军人中，包括57,332名黑人和24,743名西班牙裔美国人，我们测试了多达约3200万个与血脂水平相关的变异，并在与全球脂质遗传学联合会(Total N>；600,000)的数据进行荟萃分析后，确定了118个新的全基因组显著基因座。通过对预测会导致基因功能丧失的突变的关注和全表型相关性研究，我们提出了针对PCSK9(腹主动脉瘤)、ANGPTL4(2型糖尿病)和PDE3B(甘油三酯和冠状动脉疾病)的药物抑制剂的新适应症。
The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of U.S. military veterans. 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 1 blood lipid measurement including 57,332 blacks and 24,743 Hispanics, we tested up to ~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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遗传对人体组织基因表达的影响。
影响因子：
64.8
作者：
GTEx Consortium;Laboratory, Data Analysis &Coordinating Center (LDACC)—Analysis Working Group;Statistical Methods groups—Analysis Working Group;Enhancing GTEx (eGTEx) groups;NIH Common Fund;NIH/NCI;NIH/NHGRI;NIH/NIMH;NIH/NIDA;Biospecimen Collection Source Site—NDRI;Biospecimen Collection Source Site—RPCI;Biospecimen Core Resource—VARI;Brain Bank Repository—University of Miami Brain Endowment Bank;Leidos Biomedical—Project Management;ELSI Study;Genome Browser Data Integration &Visualization—EBI;Genome Browser Data Integration &Visualization—UCSC Genomics Institute, University of California Santa Cruz;Lead analysts:;Laboratory, Data Analysis &Coordinating Center (LDACC):;NIH program management:;Biospecimen collection:;Pathology:;eQTL manuscript working group:;Battle A;Brown CD;Engelhardt BE;Montgomery SB
通讯作者：
Montgomery SB
影响因子：
46.9
作者：
通讯作者：
--
影响因子：
24
作者：
Harrison SC;Holmes MV;Burgess S;Asselbergs FW;Jones GT;Baas AF;van 't Hof FN;de Bakker PIW;Blankensteijn JD;Powell JT;Saratzis A;de Borst GJ;Swerdlow DI;van der Graaf Y;van Rij AM;Carey DJ;Elmore JR;Tromp G;Kuivaniemi H;Sayers RD;Samani NJ;Bown MJ;Humphries SE
通讯作者：
Humphries SE
影响因子：
4.6
作者：
Below JE;Parra EJ;Gamazon ER;Torres J;Krithika S;Candille S;Lu Y;Manichakul A;Peralta-Romero J;Duan Q;Li Y;Morris AP;Gottesman O;Bottinger E;Wang XQ;Taylor KD;Ida Chen YD;Rotter JI;Rich SS;Loos RJ;Tang H;Cox NJ;Cruz M;Hanis CL;Valladares-Salgado A
通讯作者：
Valladares-Salgado A
影响因子：
4.5
作者：
Chasman DI;Paré G;Mora S;Hopewell JC;Peloso G;Clarke R;Cupples LA;Hamsten A;Kathiresan S;Mälarstig A;Ordovas JM;Ripatti S;Parker AN;Miletich JP;Ridker PM
通讯作者：
Ridker PM