Genome-wide association analysis of metabolic traits in a birth cohort from a founder population

被引：574

作者：

Sabatti, Chiara ^{[2
,3
]}

Service, Susan K. ^{[1
]}

Hartikainen, Anna-Liisa ^{[4
]}

Pouta, Anneli ^{[5
]}

Ripatti, Samuli ^{[6
]}

Brodsky, Jae ^{[3
]}

Jones, Chris G. ^{[1
,7
]}

Zaitlen, Noah A. ^{[7
]}

Varilo, Teppo ^{[8
,9
]}

Kaakinen, Marika ^{[10
]}

Sovio, Ulla

Ruokonen, Aimo ^{[12
]}

Laitinen, Jaana ^{[13
]}

Jakkula, Eveliina ^{[6
]}

Coin, Lachlan ^{[11
]}

Hoggart, Clive ^{[11
]}

Collins, Andrew ^{[14
]}

Turunen, Hannu ^{[6
]}

Gabriel, Stacey ^{[15
]}

Elliot, Paul ^{[11
]}

McCarthy, Mark I. ^{[16
,17
,18
]}

Daly, Mark J. ^{[15
,18
,19
,20
,21
,22
,23
]}

Jarvelin, Marjo-Riitta ^{[5
,11
,24
]}

Freimer, Nelson B. ^{[1
,25
,26
]}

Peltonen, Leena ^{[6
,15
,27
]}

机构：

[1] Univ Calif Los Angeles, Ctr Neurobehav Genet, Los Angeles, CA 90095 USA

[2] Univ Calif Los Angeles, Dept Human Genet, Los Angeles, CA 90095 USA

[3] Univ Calif Los Angeles, Dept Stat, Los Angeles, CA 90095 USA

[4] Univ Oulu, Dept Obstet & Gynaecol, FIN-90220 Oulu, Finland

[5] Natl Publ Hlth Inst, Dept Child & Adolescent Hlth, FIN-90101 Oulu, Finland

[6] Univ Helsinki, Inst Mol Med FIMM, FIN-00014 Helsinki, Finland

[7] Univ Calif Los Angeles, Dept Comp Sci, Los Angeles, CA 90095 USA

[8] Univ Helsinki, Dept Med Genet, Helsinki, Finland

[9] Natl Publ Hlth Inst, Biomedicum Helsinki, Dept Mol Med, Helsinki 00290, Finland

[10] Inst Hlth Sci, FIN-90220 Oulu, Finland

[11] Univ London Imperial Coll Sci Technol & Med, Dept Epidemiol & Publ Hlth, London W2 1PG, England

[12] Univ Oulu, Dept Clin Chem, FIN-90220 Oulu, Finland

[13] Finnish Inst Occupat Hlth, FIN-90220 Oulu, Finland

[14] Univ Southampton, Southampton Gen Hosp, Human Genet Res Div, Southampton SO16 6YA, Hants, England

[15] Harvard & MIT, Broad Inst, Cambridge, MA 02142 USA

[16] Univ Oxford, Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England

[17] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England

[18] Churchill Hosp, Oxford NIHR Biomed Res Ctr, Oxford OX3 7LJ, England

[19] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA

[20] Harvard Univ, Sch Med, Dept Genet, Boston, MA 02115 USA

[21] Harvard Univ, Sch Med, Dept Psychiat, Boston, MA 02115 USA

[22] Harvard Univ, Sch Med, Dept Med, Boston, MA 02115 USA

[23] Massachusetts Gen Hosp, Dept Med, Boston, MA 02114 USA

[24] Univ Oulu, Inst Hlth Sci, FIN-90014 Oulu, Finland

[25] Univ Calif Los Angeles, Jane & Terry Semel Inst Neurosci & Human Behav, Los Angeles, CA 90095 USA

[26] Univ Calif Los Angeles, Dept Psychiat, Los Angeles, CA 90095 USA

[27] Wellcome Trust Sanger Inst, Cambridge CB10 1HH, England

来源：

NATURE GENETICS | 2009年 / 41卷 / 01期

基金：

英国惠康基金;

关键词：

C-REACTIVE PROTEIN; NORTHERN FINLAND; BLOOD-PRESSURE; LINKAGE DISEQUILIBRIUM; CARDIOVASCULAR-DISEASE; LIPID CONCENTRATIONS; QUANTITATIVE TRAITS; PLASMA-GLUCOSE; RISK-FACTORS; COMMON;

D O I：

10.1038/ng.271

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Genome-wide association studies (GWAS) of longitudinal birth cohorts enable joint investigation of environmental and genetic influences on complex traits. We report GWAS results for nine quantitative metabolic traits (triglycerides, high-density lipoprotein, low-density lipoprotein, glucose, insulin, C-reactive protein, body mass index, and systolic and diastolic blood pressure) in the Northern Finland Birth Cohort 1966 (NFBC1966), drawn from the most genetically isolated Finnish regions. We replicate most previously reported associations for these traits and identify nine new associations, several of which highlight genes with metabolic functions: high-density lipoprotein with NR1H3 (LXRA), low-density lipoprotein with AR and FADS1-FADS2, glucose with MTNR1B, and insulin with PANK1. Two of these new associations emerged after adjustment of results for body mass index. Gene-environment interaction analyses suggested additional associations, which will require validation in larger samples. The currently identified loci, together with quantified environmental exposures, explain little of the trait variation in NFBC1966. The association observed between low-density lipoprotein and an infrequent variant in AR suggests the potential of such a cohort for identifying associations with both common, low-impact and rarer, high-impact quantitative trait loci.

引用

页码：35 / 46

页数：12

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