Multi-ethnic analysis of lipid-associated loci: the NHLBI CARe project.
BACKGROUND
Whereas it is well established that plasma lipid levels have substantial heritability within populations, it remains unclear how many of the genetic determinants reported in previous studies (largely performed in European American cohorts) are relevant in different ethnicities.


RESULTS
We tested a set of ∼50,000 polymorphisms from ∼2,000 candidate genes and genetic loci from genome-wide association studies (GWAS) for association with low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) in 25,000 European Americans and 9,000 African Americans in the National Heart, Lung, and Blood Institute (NHLBI) Candidate Gene Association Resource (CARe). We replicated associations for a number of genes in one or both ethnicities and identified a novel lipid-associated variant in a locus harboring ICAM1. We compared the architecture of genetic loci associated with lipids in both African Americans and European Americans and found that the same genes were relevant across ethnic groups but the specific associated variants at each gene often differed.


CONCLUSIONS
We identify or provide further evidence for a number of genetic determinants of plasma lipid levels through population association studies. In many loci the determinants appear to differ substantially between African Americans and European Americans.
Broad Institute, Cambridge, Massachusetts, United States of America.
Kiran
K
Musunuru
Simon P R
SP
Romaine
Guillaume
G
Lettre
James G
JG
Wilson
Kelly A
KA
Volcik
Michael Y
MY
Tsai
Herman A
HA
Taylor
Pamela J
PJ
Schreiner
Jerome I
JI
Rotter
Stephen S
SS
Rich
Susan
S
Redline
Bruce M
BM
Psaty
George J
GJ
Papanicolaou
Jose M
JM
Ordovas
Kiang
K
Liu
Ronald M
RM
Krauss
Nicole L
NL
Glazer
Stacey B
SB
Gabriel
Myriam
M
Fornage
L Adrienne
LA
Cupples
Sarah G
SG
Buxbaum
Eric
E
Boerwinkle
Christie M
CM
Ballantyne
Sekar
S
Kathiresan
Daniel J
DJ
Rader
D001741:Black or African American / Q000235:genetics*; D008076:Cholesterol, HDL / Q000235:genetics*; D008078:Cholesterol, LDL / Q000235:genetics*; D056726:Genetic Association Studies; D056426:Genetic Loci; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D014280:Triglycerides / Q000235:genetics*; D044465:White People / Q000235:genetics*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D014280:Triglycerides