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 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.
Willer
Cristen J
CJ
Center for Statistical Genetics, Department of Biostatistics, University of Michigan, 1420 Washington Heights, Ann Arbor, Michigan 48109, USA.
Sanna
Serena
S
Jackson
Anne U
AU
Scuteri
Angelo
A
Bonnycastle
Lori L
LL
Clarke
Robert
R
Heath
Simon C
SC
Timpson
Nicholas J
NJ
Najjar
Samer S
SS
Stringham
Heather M
HM
Strait
James
J
Duren
William L
WL
Maschio
Andrea
A
Busonero
Fabio
F
Mulas
Antonella
A
Albai
Giuseppe
G
Swift
Amy J
AJ
Morken
Mario A
MA
Narisu
Narisu
N
Bennett
Derrick
D
Parish
Sarah
S
Shen
Haiqing
H
Galan
Pilar
P
Meneton
Pierre
P
Hercberg
Serge
S
Zelenika
Diana
D
Chen
Wei-Min
WM
Li
Yun
Y
Scott
Laura J
LJ
Scheet
Paul A
PA
Sundvall
Jouko
J
Watanabe
Richard M
RM
Nagaraja
Ramaiah
R
Ebrahim
Shah
S
Lawlor
Debbie A
DA
Ben-Shlomo
Yoav
Y
Davey-Smith
George
G
Shuldiner
Alan R
AR
Collins
Rory
R
Bergman
Richard N
RN
Uda
Manuela
M
Tuomilehto
Jaakko
J
Cao
Antonio
A
Collins
Francis S
FS
Lakatta
Edward
E
Lathrop
G Mark
GM
Boehnke
Michael
M
Schlessinger
David
D
Mohlke
Karen L
KL
Abecasis
Gonçalo R
GR
D000483:Alleles; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000097:blood / Q000235:genetics*; D008078:Cholesterol, LDL / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D003198:Computer Simulation; D003324:Coronary Artery Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology; D005787:Gene Frequency; D014644:Genetic Variation; D015894:Genome, Human; D006239:Haplotypes; D006801:Humans; D016013:Likelihood Functions; D008055:Lipids / Q000097:blood / Q000235:genetics*; D008390:Markov Chains; D020641:Polymorphism, Single Nucleotide; D011336:Probability; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood / Q000235:genetics*
D008076:Cholesterol, HDL; D008078:Cholesterol, LDL; D008055:Lipids; D014280:Triglycerides