|
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| PMID |
|
|
| TITLE |
|
| Loci influencing lipid levels and coronary heart disease risk in 16 European population cohorts. |
|
| ABSTRACT |
|
|
|
| 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. |
|
| DATE PUBLISHED |
|
|
| HISTORY |
|
| PUBSTATUS |
PUBSTATUSDATE |
| received |
2008/06/27 |
| accepted |
2008/10/01 |
| aheadofprint |
2008/12/07 |
| pubmed |
2008/12/09 09:00 |
| medline |
2009/01/24 09:00 |
| entrez |
2008/12/09 09:00 |
|
| AUTHORS |
|
| NAME |
COLLECTIVENAME |
LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
AFFILIATIONINFO |
| Aulchenko YS |
|
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 S |
|
Ripatti |
Samuli |
S |
|
|
| Lindqvist I |
|
Lindqvist |
Ida |
I |
|
|
| Boomsma D |
|
Boomsma |
Dorret |
D |
|
|
| Heid IM |
|
Heid |
Iris M |
IM |
|
|
| Pramstaller PP |
|
Pramstaller |
Peter P |
PP |
|
|
| Penninx BW |
|
Penninx |
Brenda W J H |
BW |
|
|
| Janssens AC |
|
Janssens |
A Cecile J W |
AC |
|
|
| Wilson JF |
|
Wilson |
James F |
JF |
|
|
| Spector T |
|
Spector |
Tim |
T |
|
|
| Martin NG |
|
Martin |
Nicholas G |
NG |
|
|
| Pedersen NL |
|
Pedersen |
Nancy L |
NL |
|
|
| Kyvik KO |
|
Kyvik |
Kirsten Ohm |
KO |
|
|
| Kaprio J |
|
Kaprio |
Jaakko |
J |
|
|
| Hofman A |
|
Hofman |
Albert |
A |
|
|
| Freimer NB |
|
Freimer |
Nelson B |
NB |
|
|
| Jarvelin MR |
|
Jarvelin |
Marjo-Riitta |
MR |
|
|
| Gyllensten U |
|
Gyllensten |
Ulf |
U |
|
|
| Campbell H |
|
Campbell |
Harry |
H |
|
|
| Rudan I |
|
Rudan |
Igor |
I |
|
|
| Johansson A |
|
Johansson |
Asa |
A |
|
|
| Marroni F |
|
Marroni |
Fabio |
F |
|
|
| Hayward C |
|
Hayward |
Caroline |
C |
|
|
| Vitart V |
|
Vitart |
Veronique |
V |
|
|
| Jonasson I |
|
Jonasson |
Inger |
I |
|
|
| Pattaro C |
|
Pattaro |
Cristian |
C |
|
|
| Wright A |
|
Wright |
Alan |
A |
|
|
| Hastie N |
|
Hastie |
Nick |
N |
|
|
| Pichler I |
|
Pichler |
Irene |
I |
|
|
| Hicks AA |
|
Hicks |
Andrew A |
AA |
|
|
| Falchi M |
|
Falchi |
Mario |
M |
|
|
| Willemsen G |
|
Willemsen |
Gonneke |
G |
|
|
| Hottenga JJ |
|
Hottenga |
Jouke-Jan |
JJ |
|
|
| de Geus EJ |
|
de Geus |
Eco J C |
EJ |
|
|
| Montgomery GW |
|
Montgomery |
Grant W |
GW |
|
|
| Whitfield J |
|
Whitfield |
John |
J |
|
|
| Magnusson P |
|
Magnusson |
Patrik |
P |
|
|
| Saharinen J |
|
Saharinen |
Juha |
J |
|
|
| Perola M |
|
Perola |
Markus |
M |
|
|
| Silander K |
|
Silander |
Kaisa |
K |
|
|
| Isaacs A |
|
Isaacs |
Aaron |
A |
|
|
| Sijbrands EJ |
|
Sijbrands |
Eric J G |
EJ |
|
|
| Uitterlinden AG |
|
Uitterlinden |
Andre G |
AG |
|
|
| Witteman JC |
|
Witteman |
Jacqueline C M |
JC |
|
|
| Oostra BA |
|
Oostra |
Ben A |
BA |
|
|
| Elliott P |
|
Elliott |
Paul |
P |
|
|
| Ruokonen A |
|
Ruokonen |
Aimo |
A |
|
|
| Sabatti C |
|
Sabatti |
Chiara |
C |
|
|
| Gieger C |
|
Gieger |
Christian |
C |
|
|
| Meitinger T |
|
Meitinger |
Thomas |
T |
|
|
| Kronenberg F |
|
Kronenberg |
Florian |
F |
|
|
| Döring A |
|
Döring |
Angela |
A |
|
|
| Wichmann HE |
|
Wichmann |
H-Erich |
HE |
|
|
| Smit JH |
|
Smit |
Johannes H |
JH |
|
|
| McCarthy MI |
|
McCarthy |
Mark I |
MI |
|
|
| van Duijn CM |
|
van Duijn |
Cornelia M |
CM |
|
|
| Peltonen L |
|
Peltonen |
Leena |
L |
|
|
|
ENGAGE Consortium |
|
|
|
|
|
|
| INVESTIGATORS |
|
| LASTNAME |
FORENAME |
INITIALS |
AFFILIATION |
| Aulchenko |
Yurii S |
YS |
|
| 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 |
|
|
| JOURNAL |
|
| VOLUME: 41 |
| ISSUE: 1 |
| TITLE: Nature genetics |
| ISOABBREVIATION: Nat. Genet. |
| YEAR: 2009 |
| MONTH: Jan |
| DAY: |
| MEDLINEDATE: |
| SEASON: |
| CITEDMEDIUM: Internet |
| ISSN: 1546-1718 |
| ISSNTYPE: Electronic |
|
| MEDLINE JOURNAL |
|
| MEDLINETA: Nat Genet |
| COUNTRY: United States |
| ISSNLINKING: 1061-4036 |
| NLMUNIQUEID: 9216904 |
|
| PUBLICATION TYPE |
|
| PUBLICATIONTYPE TEXT |
| Journal Article |
| Research Support, N.I.H., Extramural |
| Research Support, Non-U.S. Gov't |
|
| COMMENTS AND CORRECTIONS |
|
| REFTYPE |
REFSOURCE |
REFPMID |
NOTE |
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|
| GRANTS |
|
| GRANTID |
AGENCY |
COUNTRY |
| 089061 |
Wellcome Trust |
United Kingdom |
| 5R01HL087679-02 |
NHLBI NIH HHS |
United States |
| CZB/4/710 |
Chief Scientist Office |
United Kingdom |
| MC_U127561128 |
Medical Research Council |
United Kingdom |
|
| GENERAL NOTE |
|
|
| KEYWORDS |
|
|
| MESH HEADINGS |
|
| DESCRIPTORNAME |
QUALIFIERNAME |
| Adolescent |
|
| Adult |
|
| Aged |
|
| Aged, 80 and over |
|
| Body Mass Index |
|
| Cholesterol, HDL |
blood |
| Cohort Studies |
blood |
| Coronary Disease |
genetics |
| European Continental Ancestry Group |
genetics |
| Female |
genetics |
| Genetic Predisposition to Disease |
genetics |
| Genetic Testing |
genetics |
| Genome, Human |
genetics |
| Humans |
genetics |
| Lipids |
blood |
| Male |
blood |
| Metabolic Networks and Pathways |
genetics |
| Middle Aged |
genetics |
| Phenotype |
genetics |
| Polymorphism, Single Nucleotide |
genetics |
| Quantitative Trait Loci |
genetics |
| Sex Characteristics |
genetics |
|
| SUPPLEMENTARY MESH |
|
|
| GENE SYMBOLS |
|
|
| CHEMICALS |
|
| REGISTRYNUMBER |
NAMEOFSUBSTANCE |
| 0 |
Cholesterol, HDL |
| 0 |
Lipids |
|
| OTHER ID's |
|
| OTHERID |
SOURCE |
| PMC2687074 |
NLM |
| UKMS4347 |
NLM |
|
|
