학술논문

Whole-Exome Sequencing Identifies Rare and Low-Frequency Coding Variants Associated with LDL Cholesterol
Document Type
article
Author
Lange, Leslie AHu, YounaZhang, HeXue, ChenyiSchmidt, Ellen MTang, Zheng-ZhengBizon, ChrisLange, Ethan MSmith, Joshua DTurner, Emily HJun, GooKang, Hyun MinPeloso, GinaAuer, PaulLi, Kuo-pingFlannick, JasonZhang, JiFuchsberger, ChristianGaulton, KyleLindgren, CeciliaLocke, AdamManning, AlisaSim, XuelingRivas, Manuel AHolmen, Oddgeir LGottesman, OmriLu, YingchangRuderfer, DouglasStahl, Eli ADuan, QingLi, YunDurda, PeterJiao, ShuoIsaacs, AaronHofman, AlbertBis, Joshua CCorrea, AdolfoGriswold, Michael EJakobsdottir, JohannaSmith, Albert VSchreiner, Pamela JFeitosa, Mary FZhang, QunyuanHuffman, Jennifer ECrosby, JacyWassel, Christina LDo, RonFranceschini, NoraMartin, Lisa WRobinson, Jennifer GAssimes, Themistocles LCrosslin, David RRosenthal, Elisabeth ATsai, MichaelRieder, Mark JFarlow, Deborah NFolsom, Aaron RLumley, ThomasFox, Ervin RCarlson, Christopher SPeters, UlrikeJackson, Rebecca Dvan Duijn, Cornelia MUitterlinden, André GLevy, DanielRotter, Jerome ITaylor, Herman AGudnason, VilmundurSiscovick, David SFornage, MyriamBorecki, Ingrid BHayward, CarolineRudan, IgorChen, Y EugeneBottinger, Erwin PLoos, Ruth JFSætrom, PålHveem, KristianBoehnke, MichaelGroop, LeifMcCarthy, MarkMeitinger, ThomasBallantyne, Christie MGabriel, Stacey BO’Donnell, Christopher JPost, Wendy SNorth, Kari EReiner, Alexander PBoerwinkle, EricPsaty, Bruce MAltshuler, DavidKathiresan, SekarLin, Dan-YuJarvik, Gail PCupples, L AdrienneKooperberg, CharlesWilson, James GNickerson, Deborah AAbecasis, Goncalo RRich, Stephen S
Source
American Journal of Human Genetics. 94(2)
Subject
Epidemiology
Biological Sciences
Health Sciences
Genetics
Human Genome
Prevention
Clinical Research
Heart Disease
Cardiovascular
Atherosclerosis
Aetiology
2.1 Biological and endogenous factors
Adult
Aged
Apolipoproteins E
Cholesterol
LDL
Cohort Studies
Dyslipidemias
Exome
Female
Follow-Up Studies
Gene Frequency
Genetic Code
Genome-Wide Association Study
Genotype
Humans
Lipase
Male
Middle Aged
Phenotype
Polymorphism
Single Nucleotide
Proprotein Convertase 9
Proprotein Convertases
Receptors
LDL
Sequence Analysis
DNA
Serine Endopeptidases
NHLBI Grand Opportunity Exome Sequencing Project
Medical and Health Sciences
Genetics & Heredity
Biological sciences
Biomedical and clinical sciences
Health sciences
Language
Abstract
Elevated low-density lipoprotein cholesterol (LDL-C) is a treatable, heritable risk factor for cardiovascular disease. Genome-wide association studies (GWASs) have identified 157 variants associated with lipid levels but are not well suited to assess the impact of rare and low-frequency variants. To determine whether rare or low-frequency coding variants are associated with LDL-C, we exome sequenced 2,005 individuals, including 554 individuals selected for extreme LDL-C (>98(th) or