Sex Differences in Genetic Architecture of Complex Phenotypes?

J.M. Vink, M. Bartels, C.E.M. van Beijsterveldt, J. van Dongen, J.H.D.A. van Beek, M.A. Distel, M.H.M. de Moor, D.J.A. Smit, C.C. Minica, R.S.L. Ligthart, L.M. Geels, A. Abdellaoui, C.M. Middeldorp, J.J. Hottenga, G. Willemsen, E.J.C. de Geus, D.I. Boomsma

Research output: Contribution to JournalArticleAcademicpeer-review

Abstract

We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits) in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA) studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ) same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4% of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women. © 2012 Vink et al.
Original languageEnglish
Article numbere47371
JournalPLoS ONE
Volume7
Issue number12
DOIs
Publication statusPublished - 2012

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gender differences
Sex Characteristics
Genes
Phenotype
phenotype
gender
Sample Size
Health
Genome-Wide Association Study
Electroencephalography
Psychiatry
Brain
Twin Studies
family studies
Personality Disorders
behavior disorders
Psychopathology
Growth and Development
Birth Weight
Testing

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title = "Sex Differences in Genetic Architecture of Complex Phenotypes?",
abstract = "We examined sex differences in familial resemblance for a broad range of behavioral, psychiatric and health related phenotypes (122 complex traits) in children and adults. There is a renewed interest in the importance of genotype by sex interaction in, for example, genome-wide association (GWA) studies of complex phenotypes. If different genes play a role across sex, GWA studies should consider the effect of genetic variants separately in men and women, which affects statistical power. Twin and family studies offer an opportunity to compare resemblance between opposite-sex family members to the resemblance between same-sex relatives, thereby presenting a test of quantitative and qualitative sex differences in the genetic architecture of complex traits. We analyzed data on lifestyle, personality, psychiatric disorder, health, growth, development and metabolic traits in dizygotic (DZ) same-sex and opposite-sex twins, as these siblings are perfectly matched for age and prenatal exposures. Sample size varied from slightly over 300 subjects for measures of brain function such as EEG power to over 30,000 subjects for childhood psychopathology and birth weight. For most phenotypes, sample sizes were large, with an average sample size of 9027 individuals. By testing whether the resemblance in DZ opposite-sex pairs is the same as in DZ same-sex pairs, we obtain evidence for genetic qualitative sex-differences in the genetic architecture of complex traits for 4{\%} of phenotypes. We conclude that for most traits that were examined, the current evidence is that same the genes are operating in men and women. {\circledC} 2012 Vink et al.",
author = "J.M. Vink and M. Bartels and {van Beijsterveldt}, C.E.M. and {van Dongen}, J. and {van Beek}, J.H.D.A. and M.A. Distel and {de Moor}, M.H.M. and D.J.A. Smit and C.C. Minica and R.S.L. Ligthart and L.M. Geels and A. Abdellaoui and C.M. Middeldorp and J.J. Hottenga and G. Willemsen and {de Geus}, E.J.C. and D.I. Boomsma",
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language = "English",
volume = "7",
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Sex Differences in Genetic Architecture of Complex Phenotypes? / Vink, J.M.; Bartels, M.; van Beijsterveldt, C.E.M.; van Dongen, J.; van Beek, J.H.D.A.; Distel, M.A.; de Moor, M.H.M.; Smit, D.J.A.; Minica, C.C.; Ligthart, R.S.L.; Geels, L.M.; Abdellaoui, A.; Middeldorp, C.M.; Hottenga, J.J.; Willemsen, G.; de Geus, E.J.C.; Boomsma, D.I.

In: PLoS ONE, Vol. 7, No. 12, e47371, 2012.

Research output: Contribution to JournalArticleAcademicpeer-review

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AU - Vink, J.M.

AU - Bartels, M.

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AU - van Beek, J.H.D.A.

AU - Distel, M.A.

AU - de Moor, M.H.M.

AU - Smit, D.J.A.

AU - Minica, C.C.

AU - Ligthart, R.S.L.

AU - Geels, L.M.

AU - Abdellaoui, A.

AU - Middeldorp, C.M.

AU - Hottenga, J.J.

AU - Willemsen, G.

AU - de Geus, E.J.C.

AU - Boomsma, D.I.

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