Excess of rare variants in genes identified by genome-wide association study of hypertriglyceridemia.

Nature Genetics
Christopher T JohansenRobert A Hegele

Abstract

Genome-wide association studies (GWAS) have identified multiple loci associated with plasma lipid concentrations. Common variants at these loci together explain <10% of variation in each lipid trait. Rare variants with large individual effects may also contribute to the heritability of lipid traits; however, the extent to which rare variants affect lipid phenotypes remains to be determined. Here we show an accumulation of rare variants, or a mutation skew, in GWAS-identified genes in individuals with hypertriglyceridemia (HTG). Through GWAS, we identified common variants in APOA5, GCKR, LPL and APOB associated with HTG. Resequencing of these genes revealed a significant burden of 154 rare missense or nonsense variants in 438 individuals with HTG, compared to 53 variants in 327 controls (P = 6.2 x 10(-8)), corresponding to a carrier frequency of 28.1% of affected individuals and 15.3% of controls (P = 2.6 x 10(-5)). Considering rare variants in these genes incrementally increased the proportion of genetic variation contributing to HTG.

References

Aug 1, 1995·Arteriosclerosis, Thrombosis, and Vascular Biology·D GaffneyC J Packard
Apr 9, 1999·Computer Methods and Programs in Biomedicine·M Mittlböck, M Schemper
Aug 7, 2004·Science·Jonathan C CohenHelen H Hobbs
Dec 30, 2006·PLoS Genetics·Nick PattersonDavid Reich
Mar 16, 2007·American Journal of Human Genetics·Gregory V KryukovShamil R Sunyaev
Apr 11, 2007·CMAJ : Canadian Medical Association Journal = Journal De L'Association Medicale Canadienne·George YuanRobert A Hegele
Aug 25, 2007·Arteriosclerosis, Thrombosis, and Vascular Biology·Jian WangRobert A Hegele
Nov 13, 2007·Nature Genetics·Miklós PéterfyMark H Doolittle
Jan 15, 2008·Nature Genetics·Cristen J WillerGonçalo R Abecasis
Jul 4, 2008·Human Molecular Genetics·Jian WangRobert A Hegele
Sep 10, 2008·Nature Clinical Practice. Cardiovascular Medicine·Jian WangRobert A Hegele
Dec 9, 2008·Nature Genetics·Sekar KathiresanL Adrienne Cupples
Dec 9, 2008·Nature Genetics·Yurii S AulchenkoUNKNOWN ENGAGE Consortium
Jan 14, 2009·Nature Reviews. Genetics·Robert A Hegele
Feb 10, 2009·Nature Genetics·UNKNOWN Myocardial Infarction Genetics ConsortiumDavid Altshuler
Mar 24, 2009·Arteriosclerosis, Thrombosis, and Vascular Biology·Anne P BeigneuxStephen G Young
Oct 9, 2009·Nature·Teri A ManolioPeter M Visscher
Oct 28, 2009·Nature Reviews. Genetics·Robert PlominOliver S P Davis

❮ Previous
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Citations

Mar 19, 2013·Human Genetics·Liam R Brunham, Michael R Hayden
Apr 25, 2012·Current Atherosclerosis Reports·Christopher T Johansen, Robert A Hegele
Mar 14, 2014·The Lancet. Respiratory Medicine·Michael H ChoUNKNOWN NETT Genetics, ICGN, ECLIPSE and COPDGene Investigators
Sep 13, 2012·European Journal of Human Genetics : EJHG·Daniëlla M OosterveerEric J G Sijbrands
Apr 24, 2012·Modern Pathology : an Official Journal of the United States and Canadian Academy of Pathology, Inc·Chee-Seng KuBarry Iacopetta
Jan 31, 2012·Nature Genetics·Amélie BonnefondPhilippe Froguel
May 30, 2012·Nature Genetics·Adam KiezunShamil R Sunyaev
Oct 22, 2013·Nature Genetics·Vineeta AgarwalaDavid Altshuler
Mar 8, 2011·Nature Genetics·Hilma HolmKari Stefansson
Oct 14, 2010·Nature Reviews. Genetics·Vikas BansalNicholas J Schork
Dec 2, 2010·Nature Reviews. Rheumatology·Anne B Satterthwaite, Chandra Mohan
Dec 2, 2011·The New England Journal of Medicine·Christopher J O'Donnell, Elizabeth G Nabel
Jun 5, 2012·European Heart Journal·Keyan SalariEuan A Ashley
Jul 6, 2013·European Heart Journal·Vinicius TraganteUNKNOWN SMART study group
Jul 30, 2011·The Journals of Gerontology. Series A, Biological Sciences and Medical Sciences·Friederike FlachsbartAlmut Nebel
Mar 24, 2011·Human Molecular Genetics·Jia KangUNKNOWN NIDDK IBD Genetics Consortium
Nov 2, 2011·Human Molecular Genetics·Gabe HallerAlison M Goate
Sep 20, 2012·Human Molecular Genetics·Shamil R Sunyaev
Dec 24, 2010·Current Opinion in Lipidology·Philippa J TalmudSteve E Humphries
Apr 27, 2011·Current Opinion in Lipidology·Christopher T Johansen, Robert A Hegele
Mar 16, 2012·Current Opinion in Lipidology·Cristen J Willer, Karen L Mohlke
Jun 14, 2012·Current Opinion in Lipidology·Daniel GaudetJohn Kastelein
Jun 28, 2011·Genome Research·Mark YandellMartin G Reese
Feb 1, 2011·Respirology : Official Journal of the Asian Pacific Society of Respirology·Loubna Akhabir, Andrew J Sandford
Oct 10, 2012·European Journal of Neurology : the Official Journal of the European Federation of Neurological Societies·M B HammerA B Singleton
Apr 30, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Ira J GoldbergRuth McPherson
May 21, 2011·Arteriosclerosis, Thrombosis, and Vascular Biology·Christopher T JohansenRobert A Hegele
Jan 19, 2013·Arteriosclerosis, Thrombosis, and Vascular Biology·Vineeta SharmaRobert O Ryan
Dec 3, 2011·Circulation. Cardiovascular Genetics·Christopher T JohansenRobert A Hegele
Sep 1, 2012·American Journal of Respiratory and Critical Care Medicine·Ivana V Yang, David A Schwartz

❮ Previous
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