Newly identified loci that influence lipid concentrations and risk of coronary artery disease
To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes a...
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Published in | Nature genetics Vol. 40; no. 2; pp. 161 - 169 |
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Main Authors | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
Format | Journal Article |
Language | English |
Published |
New York
Nature Publishing Group US
01.02.2008
Nature Publishing Group |
Subjects | |
Online Access | Get full text |
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Summary: | To identify genetic variants influencing plasma lipid concentrations, we first used genotype imputation and meta-analysis to combine three genome-wide scans totaling 8,816 individuals and comprising 6,068 individuals specific to our study (1,874 individuals from the FUSION study of type 2 diabetes and 4,184 individuals from the SardiNIA study of aging-associated variables) and 2,758 individuals from the Diabetes Genetics Initiative, reported in a companion study in this issue. We subsequently examined promising signals in 11,569 additional individuals. Overall, we identify strongly associated variants in eleven loci previously implicated in lipid metabolism (
ABCA1
, the
APOA5-APOA4-APOC3-APOA1
and
APOE-APOC
clusters,
APOB
,
CETP
,
GCKR
,
LDLR
,
LPL
,
LIPC
,
LIPG
and
PCSK9
) and also in several newly identified loci (near
MVK-MMAB
and
GALNT2
, with variants primarily associated with high-density lipoprotein (HDL) cholesterol; near
SORT1
, with variants primarily associated with low-density lipoprotein (LDL) cholesterol; near
TRIB1
,
MLXIPL
and
ANGPTL3
, with variants primarily associated with triglycerides; and a locus encompassing several genes near
NCAN
, with variants strongly associated with both triglycerides and LDL cholesterol). Notably, the 11 independent variants associated with increased LDL cholesterol concentrations in our study also showed increased frequency in a sample of coronary artery disease cases versus controls. |
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Bibliography: | ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to the work |
ISSN: | 1061-4036 1546-1718 |
DOI: | 10.1038/ng.76 |