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  • Original Article
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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

International Journal of Obesity volume 33, pages 1235–1242 (2009)Cite this article

Abstract

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 ∼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.

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Acknowledgements

This project is supported by the European Commission under the program ‘Quality of Life and Management of the Living Resources’ of 5th Framework Programme (no. QLG2-CT-2002-01254), Genome-Wide Analyses of European Twin and Population Cohorts (EU/QLRT-2001-01254), NIH/NHLBI: STAMPEED (Genetics of cardiovascular risk factors in large founder population birth cohorts, 1-R01-HL087679-01), by the Finnish Heart Association, the Sigrid Juselius Foundation and the Academy of Finland Centre of Excellence in Complex Disease Genetics. TwinsUK is supported by the Wellcome Trust, the BBSRC and an NHS NIHR Biomedical research centre Grant to KCL and Guys and St Thomas' foundation hospitals trust. The Swedish twin registry was supported by Swedish Research Council (no. M-2005-1112) and the Swedish Foundation for Strategic Research. The Australian Twin Registry was supported in part by Grants from NIAAA (USA): AA007535, AA013320, AA013326, AA014041, AA07728, AA10249, AA11998, and NHMRC (Australia): 941177, 951023, 950998, 981339, 241916 and 941944. The Netherlands Twin Register was supported by the Netherlands Heart Foundation (86.083, 88.042, 90.313), the Netherlands Organisation for Scientific Research (904-61-090; SPI 56-464-14192; 480-04-004), Center Medical Systems Biology (NWO Genomics), Genome Scan for Neuroticism (National Institute of Mental Health Grant no. R01 MH059160). Samples were genotyped by the Mammalian Genotyping Service in Marshfield and the Molecular Epidemiology Section, Leiden University Medical Centre. The Danish Twin Registry has been supported by the Danish Medical Research Council, The Danish Diabetes Foundation, the Danish Heart Foundation and the Novo Nordisk Foundation.

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Authors and Affiliations

  1. Department of Human Genetics, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridge, UK

    J Kettunen, A Palotie & L Peltonen

  2. Department of Chronic Disease Prevention, National Institute for Health and Welfare, Helsinki, Finland

    J Kettunen, M Perola & L Peltonen

  3. Institute for Molecular Medicine FIMM, Helsinki, Finland

    J Kettunen, M Perola, E Widen, J Kaprio, A Palotie & L Peltonen

  4. Department of Medical Genetics, Faculty of Medicine, University of Helsinki, Helsinki, Finland

    M Perola & L Peltonen

  5. Queensland Institute of Medical Research, Brisbane, Australia

    N G Martin, B K Cornes, G W Montgomery & B Benyamin

  6. Department of Twin Research and Genetic Epidemiology, King's College London, London, UK

    S G Wilson, T Andrew & T D Spector

  7. School of Medicine and Pharmacology, The University of Western Australia, Crawley, Western Australia, Australia

    S G Wilson

  8. Norwegian Institute of Public Health, Oslo, Norway

    J R Harris

  9. Department of Biological Psychology, Free University, Amsterdam, The Netherlands

    D Boomsma, G Willemsen & J-J Hottenga

  10. Department of Molecular Epidemiology, Leiden University Medical Center, Leiden, The Netherlands

    P E Slagboom

  11. The Danish Twin Registry, Institute of Public Health, University of Southern Denmark, Odense, Denmark

    K Christensen & K O Kyvik

  12. Institute of Regional Health Services Research, University of Southern Denmark, Odense, Denmark

    K O Kyvik

  13. The Institute of Preventive Medicine, Copenhagen University Hospital, Copenhagen, Denmark

    T I A Sørensen

  14. Karolinska Institutet, Stockholm, Sweden

    N L Pedersen & P K E Magnusson

  15. Department of Public Health, Faculty of Medicine, University of Helsinki, Helsinki, Finland

    K Silventoinen & J Kaprio

  16. Department of Mental Health, National Institute for Health and Welfare, Helsinki, Finland

    J Kaprio

  17. Department of Clinical Chemistry, University of Helsinki, Helsinki, Finland

    A Palotie

  18. The Broad Institute, MIT, Boston, MA, USA

    A Palotie & L Peltonen

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  1. J Kettunen
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  2. M Perola
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  3. N G Martin
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  18. T Andrew
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  19. T D Spector
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  20. E Widen
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Kettunen, J., Perola, M., Martin, N. et al. 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. Int J Obes 33, 1235–1242 (2009). https://doi.org/10.1038/ijo.2009.168

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