Multicenter dizygotic twin cohort study confirms two linkage susceptibility loci for body mass index at 3q29 and 7q36 and identifies three further potential novel loci

被引：19

作者：

Kettunen, J. ^{[1
,2
,3
]}

Perola, M. ^{[2
,3
,4
]}

Martin, N. G. ^{[5
]}

Cornes, B. K. ^{[5
]}

Wilson, S. G. ^{[6
,7
]}

Montgomery, G. W. ^{[5
]}

Benyamin, B. ^{[5
]}

Harris, J. R. ^{[8
]}

Boomsma, D. ^{[9
]}

Willemsen, G. ^{[9
]}

Hottenga, J-J ^{[9
]}

Slagboom, P. E. ^{[10
]}

Christensen, K. ^{[11
]}

Kyvik, K. O. ^{[11
,12
]}

Sorensen, T. I. A. ^{[13
]}

Pedersen, N. L. ^{[14
]}

Magnusson, P. K. E. ^{[14
]}

Andrew, T. ^{[6
]}

Spector, T. D. ^{[6
]}

Widen, E. ^{[3
]}

Silventoinen, K. ^{[15
]}

Kaprio, J. ^{[3
,15
,16
]}

Palotie, A. ^{[1
,3
,17
,18
]}

Peltonen, L. ^{[1
,2
,3
,4
,18
]}

机构：

[1] Wellcome Trust Sanger Inst, Dept Human Genet, Cambridge CB10 1HH, England

[2] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland

[3] Inst Mol Med FIMM, Helsinki, Finland

[4] Univ Helsinki, Dept Med Genet, Fac Med, Helsinki, Finland

[5] Queensland Inst Med Res, Brisbane, Qld 4006, Australia

[6] Kings Coll London, Dept Twin Res & Genet Epidemiol, London WC2R 2LS, England

[7] Univ Western Australia, Sch Med & Pharmacol, Crawley, WA, Australia

[8] Norwegian Inst Publ Hlth, Oslo, Norway

[9] Free Univ Amsterdam, Dept Biol Psychol, Amsterdam, Netherlands

[10] Leiden Univ, Med Ctr, Dept Mol Epidemiol, Leiden, Netherlands

[11] Univ So Denmark, Inst Publ Hlth, Danish Twin Registry, Odense, Denmark

[12] Univ So Denmark, Inst Reg Hlth Serv Res, Odense, Denmark

[13] Univ Copenhagen Hosp, Inst Prevent Med, DK-2100 Copenhagen, Denmark

[14] Karolinska Inst, Stockholm, Sweden

[15] Univ Helsinki, Dept Publ Hlth, Fac Med, Helsinki, Finland

[16] Natl Inst Hlth & Welf, Dept Mental Hlth, Helsinki, Finland

[17] Univ Helsinki, Dept Clin Chem, SF-00100 Helsinki, Finland

[18] MIT, Broad Inst, Boston, MA USA

来源：

INTERNATIONAL JOURNAL OF OBESITY | 2009年 / 33卷 / 11期

基金：

英国惠康基金; 英国生物技术与生命科学研究理事会; 芬兰科学院; 澳大利亚国家健康与医学研究理事会; 瑞典研究理事会; 英国医学研究理事会;

关键词：

genetic linkage; body mass index; dizygotic twins; quantitative trait locus; heritability; GENOME-WIDE SCAN; QUANTITATIVE-TRAIT-LOCUS; HUMAN OBESITY; ENVIRONMENTAL-FACTORS; EARLY-ONSET; FTO GENE; FAT MASS; BMI; ASSOCIATION; VARIANTS;

D O I：

10.1038/ijo.2009.168

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective: To identify common loci and potential genetic variants affecting body mass index (BMI, kg m(-2)) in study populations originating from Europe. Design: We combined genome-wide linkage scans of six cohorts from Australia, Denmark, Finland, the Netherlands, Sweden and the United Kingdom with an similar to 10-cM microsatellite marker map. Variance components linkage analysis was carried out with age, sex and country of origin as covariates. Subjects: The GenomEUtwin consortium consists of twin cohorts from eight countries (Australia, Denmark, the Netherlands, Finland, Italy, Norway, Sweden and the United Kingdom) with a total data collection of more than 500 000 monozygotic and dizygotic (DZ) twin pairs. Variance due to early-life events and the environment is reduced within twin pairs, which makes DZ pairs highly valuable for linkage studies of complex traits. This study totaled 4401 European-originated twin families (10 535 individuals) from six countries (Australia, Denmark, the Netherlands, Finland, Sweden and the United Kingdom). Results: We found suggestive evidence for a quantitative trait locus on 3q29 and 7q36 in the combined sample of DZ twins (multipoint logarithm of odds score (MLOD) 2.6 and 2.4, respectively). Two individual cohorts showed strong evidence independently for three additional loci: 16q23 (MLOD = 3.7) and 2p24 (MLOD = 3.4) in the Dutch cohort and 20q13 (MLOD = 3.2) in the Finnish cohort. Conclusion: Linkage analysis of the combined data in this large twin cohort study provided evidence for suggestive linkage to BMI. In addition, two cohorts independently provided significant evidence of linkage to three new loci. The results of our study suggest a smaller environmental variance between DZ twins than full siblings, with a corresponding increase in heritability for BMI as well as an increase in linkage signal in well-replicated regions. The results are consistent with the possibility of locus heterogeneity for some genomic regions, and indicate a lack of major common quantitative trait locus variants affecting BMI in European populations. International Journal of Obesity (2009) 33, 1235-1242; doi:10.1038/ijo.2009.168; published online 1 September 2009

引用

页码：1235 / 1242

页数：8

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