Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts.
Recent genome-wide association (GWA) studies of lipids have been conducted in samples ascertained for other phenotypes, particularly diabetes. Here we report the first GWA analysis of loci affecting total cholesterol (TC), low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol and triglycerides sampled randomly from 16 population-based cohorts and genotyped using mainly the Illumina HumanHap300-Duo platform. Our study included a total of 17,797-22,562 persons, aged 18-104 years and from geographic regions spanning from the Nordic countries to Southern Europe. We established 22 loci associated with serum lipid levels at a genome-wide significance level (P < 5 x 10(-8)), including 16 loci that were identified by previous GWA studies. The six newly identified loci in our cohort samples are ABCG5 (TC, P = 1.5 x 10(-11); LDL, P = 2.6 x 10(-10)), TMEM57 (TC, P = 5.4 x 10(-10)), CTCF-PRMT8 region (HDL, P = 8.3 x 10(-16)), DNAH11 (LDL, P = 6.1 x 10(-9)), FADS3-FADS2 (TC, P = 1.5 x 10(-10); LDL, P = 4.4 x 10(-13)) and MADD-FOLH1 region (HDL, P = 6 x 10(-11)). For three loci, effect sizes differed significantly by sex. Genetic risk scores based on lipid loci explain up to 4.8% of variation in lipids and were also associated with increased intima media thickness (P = 0.001) and coronary heart disease incidence (P = 0.04). The genetic risk score improves the screening of high-risk groups of dyslipidemia over classical risk factors.
Aulchenko
Yurii S
YS
[1] Department of Epidemiology and Biostatistics, Erasmus University Medical Center, P.O. Box 2040, 3000 CA Rotterdam, The Netherlands. [2] These authors contributed equally to this work.
Ripatti
Samuli
S
Lindqvist
Ida
I
Boomsma
Dorret
D
Heid
Iris M
IM
Pramstaller
Peter P
PP
Penninx
Brenda W J H
BW
Janssens
A Cecile J W
AC
Wilson
James F
JF
Spector
Tim
T
Martin
Nicholas G
NG
Pedersen
Nancy L
NL
Kyvik
Kirsten Ohm
KO
Kaprio
Jaakko
J
Hofman
Albert
A
Freimer
Nelson B
NB
Jarvelin
Marjo-Riitta
MR
Gyllensten
Ulf
U
Campbell
Harry
H
Rudan
Igor
I
Johansson
Asa
A
Marroni
Fabio
F
Hayward
Caroline
C
Vitart
Veronique
V
Jonasson
Inger
I
Pattaro
Cristian
C
Wright
Alan
A
Hastie
Nick
N
Pichler
Irene
I
Hicks
Andrew A
AA
Falchi
Mario
M
Willemsen
Gonneke
G
Hottenga
Jouke-Jan
JJ
de Geus
Eco J C
EJ
Montgomery
Grant W
GW
Whitfield
John
J
Magnusson
Patrik
P
Saharinen
Juha
J
Perola
Markus
M
Silander
Kaisa
K
Isaacs
Aaron
A
Sijbrands
Eric J G
EJ
Uitterlinden
Andre G
AG
Witteman
Jacqueline C M
JC
Oostra
Ben A
BA
Elliott
Paul
P
Ruokonen
Aimo
A
Sabatti
Chiara
C
Gieger
Christian
C
Meitinger
Thomas
T
Kronenberg
Florian
F
Döring
Angela
A
Wichmann
H-Erich
HE
Smit
Johannes H
JH
McCarthy
Mark I
MI
van Duijn
Cornelia M
CM
Peltonen
Leena
L
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D015331:Cohort Studies; D003327:Coronary Disease / Q000097:blood* / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D015894:Genome, Human / Q000235:genetics; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D053858:Metabolic Networks and Pathways / Q000235:genetics; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D040641:Quantitative Trait Loci / Q000235:genetics*; D012727:Sex Characteristics; D044465:White People / Q000235:genetics*
D008076:Cholesterol, HDL; D008055:Lipids