Genetic Epidemiology, Translational Neurogenomics, Psychiatric Genetics and Statistical Genetics Laboratories investigate the pattern of disease in families, particularly identical and non-identical twins, to assess the relative importance of genes and environment in a variety of important health problems.
QIMR Home Page
GenEpi Home Page
Publications
Contacts
Research
Staff Index
Collaborators
Software Tools
Computing Resources
Studies
Search
GenEpi Intranet
PMID
19060911
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
2009 Jan
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
Cites Bioinformatics. 2007 May 15;23(10):1294-6 17384015
Cites Science. 2007 Jun 1;316(5829):1341-5 17463248
Cites BMC Med Genet. 2007;8:29 17550581
Cites Am J Hum Genet. 2007 Sep;81(3):559-75 17701901
Cites Eur J Epidemiol. 2007;22(11):819-29 17955331
Cites Heart. 2008 Jan;94(1):34-9 17916661
Cites Am J Hum Genet. 2008 Jan;82(1):139-49 18179892
Cites Nat Genet. 2008 Feb;40(2):161-9 18193043
Cites Nat Genet. 2008 Feb;40(2):189-97 18193044
Cites Nat Genet. 2008 Feb;40(2):149-51 18193046
Cites Lancet. 2008 Feb 9;371(9611):483-91 18262040
Cites Eur J Hum Genet. 2008 Mar;16(3):335-42 18197199
Cites N Engl J Med. 2008 Mar 20;358(12):1240-9 18354102
Cites Curr Opin Lipidol. 2008 Apr;19(2):122-7 18388691
Cites Nutr Rev. 2008 Jun;66(6):343-8 18522623
Cites Hum Mol Genet. 2008 Oct 15;17(R2):R166-73 18852206
Cites Nat Genet. 2009 Jan;41(1):35-46 19060910
Cites Circ Cardiovasc Genet. 2008 Oct;1(1):10-20 20031538
Cites Am J Hum Genet. 2007 Dec;81(6):1278-83 17966091
Cites Endocrinol Metab Clin North Am. 2003 Dec;32(4):855-67 14711065
Cites JAMA. 2004 Jun 16;291(23):2821-7 15199031
Cites Acta Paediatr Scand. 1969;193:Suppl 193:1+ 4911003
Cites Clin Chem. 1972 Jun;18(6):499-502 4337382
Cites Lancet. 1975 May 3;1(7914):1033 48701
Cites Am J Hum Genet. 1985 Mar;37(2):268-85 3985008
Cites Adv Exp Med Biol. 1986;201:151-62 2432761
Cites Am Heart J. 1991 Jan;121(1 Pt 2):293-8 1985385
Cites J Lipid Res. 1992 Nov;33(11):1569-82 1464741
Cites Am J Hum Genet. 1997 Jun;60(6):1502-12 9199573
Cites Ann Intern Med. 1961 Jul;55:33-50 13751193
Cites Ann Hum Genet. 2005 May;69(Pt 3):288-95 15845033
Cites Gesundheitswesen. 2005 Aug;67 Suppl 1:S26-30 16032514
Cites Nat Methods. 2006 Jan;3(1):31-3 16369550
Cites Coll Antropol. 1999 Dec;23(2):531-46 10646227
Cites Am J Hum Genet. 2000 Jun;66(6):1933-44 10801388
Cites Twin Res. 2003 Oct;6(5):354-60 14624719
Cites Nat Genet. 2006 Feb;38(2):218-22 16429159
Cites Nat Genet. 2006 Aug;38(8):904-9 16862161
Cites PLoS Genet. 2006 Aug 25;2(8):e132 16934002
CommentIn Nat Genet. 2009 Jan;41(1):5-6 19112455
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