Six New Loci Associated with Blood Low-density Lipoprotein Cholesterol, High-density Lipoprotein Cholesterol or Triglycerides in Humans

Overview

Journal Nat Genet

Specialty Genetics

Date 2008 Jan 15

PMID 18193044

Citations 733

Authors

Sekar Kathiresan

Olle Melander

Candace Guiducci

Aarti Surti

Noel P Burtt

Mark J Rieder

Gregory M Cooper

Charlotta Roos

Benjamin F Voight

Aki S Havulinna

Bjorn Wahlstrand

Thomas Hedner

Dolores Corella

E Shyong Tai

Jose M Ordovas

Goran Berglund

Erkki Vartiainen

Pekka Jousilahti

Bo Hedblad

Marja-Riitta Taskinen

Christopher Newton-Cheh

Veikko Salomaa

Leena Peltonen

Leif Groop

David M Altshuler

Marju Orho-Melander

Affiliations

Soon will be listed here.

Abstract

Blood concentrations of lipoproteins and lipids are heritable risk factors for cardiovascular disease. Using genome-wide association data from three studies (n = 8,816 that included 2,758 individuals from the Diabetes Genetics Initiative specific to the current paper as well as 1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables reported in a companion paper in this issue) and targeted replication association analyses in up to 18,554 independent participants, we show that common SNPs at 18 loci are reproducibly associated with concentrations of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, and/or triglycerides. Six of these loci are new (P < 5 x 10(-8) for each new locus). Of the six newly identified chromosomal regions, two were associated with LDL cholesterol (1p13 near CELSR2, PSRC1 and SORT1 and 19p13 near CILP2 and PBX4), one with HDL cholesterol (1q42 in GALNT2) and five with triglycerides (7q11 near TBL2 and MLXIPL, 8q24 near TRIB1, 1q42 in GALNT2, 19p13 near CILP2 and PBX4 and 1p31 near ANGPTL3). At 1p13, the LDL-associated SNP was also strongly correlated with CELSR2, PSRC1, and SORT1 transcript levels in human liver, and a proxy for this SNP was recently shown to affect risk for coronary artery disease. Understanding the molecular, cellular and clinical consequences of the newly identified loci may inform therapy and clinical care.

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