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

J. Kettunen, M. Perola, N. G. Martin, B. K. Cornes, S. G. Wilson, G. W. Montgomery, Beben Benyamin, J. R. Harris, D. Boomsma, G. Willemsen, J. J. Hottenga, P. E. Slagboom, K. Christensen, K. O. Kyvik, T. I.A. Sørensen, N. L. Pedersen, P. K.E. Magnusson, T. Andrew, T. D. Spector, E. Widen & 4 others K. Silventoinen, J. Kaprio, A. Palotie, L. Peltonen

Research output: Contribution to journalArticle

17 Citations (Scopus)

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 (MLOD3.7) and 2p24 (MLOD3.4) in the Dutch cohort and 20q13 (MLOD3.2) 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.

LanguageEnglish
Pages1235-1242
Number of pages8
JournalInternational Journal of Obesity
Volume33
Issue number11
DOIs
Publication statusPublished - 2 Sep 2009

Keywords

  • Body mass index
  • Dizygotic twins
  • Genetic linkage
  • Heritability
  • Quantitative trait locus

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics

Cite this

Kettunen, J. ; Perola, M. ; Martin, N. G. ; Cornes, B. K. ; Wilson, S. G. ; Montgomery, G. W. ; Benyamin, Beben ; Harris, J. R. ; Boomsma, D. ; Willemsen, G. ; Hottenga, J. J. ; Slagboom, P. E. ; Christensen, K. ; Kyvik, K. O. ; Sørensen, T. I.A. ; Pedersen, N. L. ; Magnusson, P. K.E. ; Andrew, T. ; Spector, T. D. ; Widen, E. ; Silventoinen, K. ; Kaprio, J. ; Palotie, A. ; Peltonen, L. / 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. In: International Journal of Obesity. 2009 ; Vol. 33, No. 11. pp. 1235-1242.
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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 (MLOD3.7) and 2p24 (MLOD3.4) in the Dutch cohort and 20q13 (MLOD3.2) 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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author = "J. Kettunen and M. Perola and Martin, {N. G.} and Cornes, {B. K.} and Wilson, {S. G.} and Montgomery, {G. W.} and Beben Benyamin and Harris, {J. R.} and D. Boomsma and G. Willemsen and Hottenga, {J. J.} and Slagboom, {P. E.} and K. Christensen and Kyvik, {K. O.} and S{\o}rensen, {T. I.A.} and Pedersen, {N. L.} and Magnusson, {P. K.E.} and T. Andrew and Spector, {T. D.} and E. Widen and K. Silventoinen and J. Kaprio and A. Palotie and L. Peltonen",
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Kettunen, J, Perola, M, Martin, NG, Cornes, BK, Wilson, SG, Montgomery, GW, Benyamin, B, Harris, JR, Boomsma, D, Willemsen, G, Hottenga, JJ, Slagboom, PE, Christensen, K, Kyvik, KO, Sørensen, TIA, Pedersen, NL, Magnusson, PKE, Andrew, T, Spector, TD, Widen, E, Silventoinen, K, Kaprio, J, Palotie, A & Peltonen, L 2009, '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, vol. 33, no. 11, pp. 1235-1242. https://doi.org/10.1038/ijo.2009.168

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. / Kettunen, J.; Perola, M.; Martin, N. G.; Cornes, B. K.; Wilson, S. G.; Montgomery, G. W.; Benyamin, Beben; Harris, J. R.; Boomsma, D.; Willemsen, G.; Hottenga, J. J.; Slagboom, P. E.; Christensen, K.; Kyvik, K. O.; Sørensen, T. I.A.; Pedersen, N. L.; Magnusson, P. K.E.; Andrew, T.; Spector, T. D.; Widen, E.; Silventoinen, K.; Kaprio, J.; Palotie, A.; Peltonen, L.

In: International Journal of Obesity, Vol. 33, No. 11, 02.09.2009, p. 1235-1242.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 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

AU - Kettunen, J.

AU - Perola, M.

AU - Martin, N. G.

AU - Cornes, B. K.

AU - Wilson, S. G.

AU - Montgomery, G. W.

AU - Benyamin, Beben

AU - Harris, J. R.

AU - Boomsma, D.

AU - Willemsen, G.

AU - Hottenga, J. J.

AU - Slagboom, P. E.

AU - Christensen, K.

AU - Kyvik, K. O.

AU - Sørensen, T. I.A.

AU - Pedersen, N. L.

AU - Magnusson, P. K.E.

AU - Andrew, T.

AU - Spector, T. D.

AU - Widen, E.

AU - Silventoinen, K.

AU - Kaprio, J.

AU - Palotie, A.

AU - Peltonen, L.

PY - 2009/9/2

Y1 - 2009/9/2

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AB - 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 (MLOD3.7) and 2p24 (MLOD3.4) in the Dutch cohort and 20q13 (MLOD3.2) 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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KW - Dizygotic twins

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