Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program.
Derek KlarinScott M DamrauerKelly ChoYan V SunTanya M TeslovichJacqueline HonerlawDavid R GagnonScott L DuVallJin LiGina M PelosoMark D ChaffinAeron M SmallJie HuangHua TangJulie A LynchYuk-Lam HoDajiang J LiuConnor A EmdinAlexander H LiJennifer E HuffmanJennifer S LeePradeep NatarajanRajiv ChowdhuryDanish SaleheenMarijana VujkovicAris BarasSaiju PyarajanEmanuele Di AngelantonioBenjamin M NealeAliya NaheedAmit V KheraJohn DaneshKyong-Mi ChangGonçalo AbecasisCristen J WillerFrederick E DeweyDavid J Careynull nullnull nullnull nullnull nullJohn ConcatoJ Michael GazianoChristopher J O'DonnellPhilip S TsaoSekar KathiresanDaniel J RaderPeter W F WilsonThemistocles L AssimesPublished in: Nature genetics (2018)
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).
Keyphrases
- electronic health record
- genome wide
- quality improvement
- copy number
- abdominal aortic aneurysm
- dna methylation
- type diabetes
- fatty acid
- systematic review
- clinical decision support
- healthcare
- adverse drug
- coronary artery
- public health
- mental health
- coronary artery disease
- high throughput
- cancer therapy
- big data
- randomized controlled trial
- glycemic control
- metabolic syndrome
- drug delivery
- high density
- transcatheter aortic valve replacement
- atrial fibrillation
- adipose tissue
- aortic stenosis
- machine learning
- data analysis
- genome wide association