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, GW Montgomery, B. Benyamin, J.R. Harris, D.I. Boomsma, G. Willemsen, J.J. Hottenga, P.E. Slagboom, K. Christensen, K. Kyvik, T.I.A. Sorensen, 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 JournalArticleAcademicpeer-review

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. © 2009 Macmillan Publishers Limited All rights reserved.
Original languageEnglish
Pages (from-to)1235-1242
JournalInternational Journal of Obesity
Volume33
Issue number11
DOIs
Publication statusPublished - 2009

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Dizygotic Twins
Twin Studies
Denmark
Finland
Sweden
Netherlands
Body Mass Index
Cohort Studies
Quantitative Trait Loci
Genetic Loci
Monozygotic Twins
Norway
Microsatellite Repeats
Italy
Population
Siblings
Genome
United Kingdom

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Kettunen, J. ; Perola, M. ; Martin, N.G. ; Cornes, B.K. ; Wilson, S.G. ; Montgomery, GW ; Benyamin, B. ; Harris, J.R. ; Boomsma, D.I. ; Willemsen, G. ; Hottenga, J.J. ; Slagboom, P.E. ; Christensen, K. ; Kyvik, K. ; Sorensen, 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.
@article{0427c0b3421448288f43200f53297171,
title = "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",
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. {\circledC} 2009 Macmillan Publishers Limited All rights reserved.",
author = "J. Kettunen and M. Perola and N.G. Martin and B.K. Cornes and S.G. Wilson and GW Montgomery and B. Benyamin and J.R. Harris and D.I. Boomsma and G. Willemsen and J.J. Hottenga and P.E. Slagboom and K. Christensen and K. Kyvik and T.I.A. Sorensen and N.L. Pedersen and P.K.E. Magnusson and T. Andrew and T.D. Spector and E. Widen and K. Silventoinen and J. Kaprio and A. Palotie and L. Peltonen",
year = "2009",
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pages = "1235--1242",
journal = "International Journal of Obesity",
issn = "0307-0565",
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Kettunen, J, Perola, M, Martin, NG, Cornes, BK, Wilson, SG, Montgomery, GW, Benyamin, B, Harris, JR, Boomsma, DI, Willemsen, G, Hottenga, JJ, Slagboom, PE, Christensen, K, Kyvik, K, Sorensen, 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, GW; Benyamin, B.; Harris, J.R.; Boomsma, D.I.; Willemsen, G.; Hottenga, J.J.; Slagboom, P.E.; Christensen, K.; Kyvik, K.; Sorensen, 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, 2009, p. 1235-1242.

Research output: Contribution to JournalArticleAcademicpeer-review

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, GW

AU - Benyamin, B.

AU - Harris, J.R.

AU - Boomsma, D.I.

AU - Willemsen, G.

AU - Hottenga, J.J.

AU - Slagboom, P.E.

AU - Christensen, K.

AU - Kyvik, K.

AU - Sorensen, 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

Y1 - 2009

N2 - 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. © 2009 Macmillan Publishers Limited All rights reserved.

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. © 2009 Macmillan Publishers Limited All rights reserved.

U2 - 10.1038/ijo.2009.168

DO - 10.1038/ijo.2009.168

M3 - Article

VL - 33

SP - 1235

EP - 1242

JO - International Journal of Obesity

JF - International Journal of Obesity

SN - 0307-0565

IS - 11

ER -