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.
authors.affiliation: Netherlands Twin Register, Department of Biological Psychology, VU University Amsterdam, Amsterdam, The Netherlands. jm.vink@vu.nl
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Vink
authors.forename: Meike
authors.initials: M
authors.lastname: Bartels
authors.forename: Toos C E M
authors.initials: TC
authors.lastname: van Beijsterveldt
authors.forename: Jenny
authors.initials: J
authors.lastname: van Dongen
authors.forename: Jenny H D A
authors.initials: JH
authors.lastname: van Beek
authors.forename: Marijn A
authors.initials: MA
authors.lastname: Distel
authors.forename: Marleen H M
authors.initials: MH
authors.lastname: de Moor
authors.forename: Dirk J A
authors.initials: DJ
authors.lastname: Smit
authors.forename: Camelia C
authors.initials: CC
authors.lastname: Minica
authors.forename: Lannie
authors.initials: L
authors.lastname: Ligthart
authors.forename: Lot M
authors.initials: LM
authors.lastname: Geels
authors.forename: Abdel
authors.initials: A
authors.lastname: Abdellaoui
authors.forename: Christel M
authors.initials: CM
authors.lastname: Middeldorp
authors.forename: Jouke Jan
authors.initials: JJ
authors.lastname: Hottenga
authors.forename: Gonneke
authors.initials: G
authors.lastname: Willemsen
authors.forename: Eco J C
authors.initials: EJ
authors.lastname: de Geus
authors.forename: Dorret I
authors.initials: DI
authors.lastname: Boomsma
mesh_terms: D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking; D000886:Anthropometry / Q000379:methods; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography / Q000379:methods; D005260:Female; D005821:Genetic Techniques; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008019:Life Style; D008297:Male; D008881:Migraine Disorders / Q000235:genetics; D008957:Models, Genetic; D015233:Models, Statistical; D010641:Phenotype; D012307:Risk Factors; D012727:Sex Characteristics; D014429:Twins, Dizygotic; D014430:Twins, Monozygotic