Sex differences in genetic architecture of complex phenotypes?
- Authors
- Vink, Jacqueline M; Bartels, Meike; van Beijsterveldt, Toos C E M; van Dongen, Jenny; van Beek, Jenny H D A; Distel, Marijn A; de Moor, Marleen H M; Smit, Dirk J A; Minica, Camelia C; Ligthart, Lannie; Geels, Lot M; Abdellaoui, Abdel; Middeldorp, Christel M; Hottenga, Jouke Jan; Willemsen, Gonneke; de Geus, Eco J C; Boomsma, Dorret I
- Year
- 2012
- Journal
- PloS one
- PMID
- 23272036
- DOI
- 10.1371/journal.pone.0047371
- PMCID
- PMC3525575
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.
Twin correlations for Lifestyle variables.1A: adult twins and 1B: adolescent twins. The green bars represent correlations in Monozygotic Male (MZM) twin pairs (light green) and Monozygotic Female (MZF) twin pairs. The blue bars represent correlations in Dizygotic Male (DZM) twin pairs, Dizygotic Female (DZF) twin pairs and Dizygotic Opposite Sex (DOS) twin pairs. The green and blue bars reflect the correlations in a full model, while the orange bars reflect twin correlations for Dizygotic (DZ) twin pairs in the most parsimonious model, with: DZM (light orange), MZF (normal orange), DOS (dark orange).
Twin correlations for Behavioral and Emotional Problems.1A: adult psychiatry, 1B: adult psychology, 1C Internalizing behavior in children, 1D Externalizing behavior in children, 1E other scales in children. The green bars represent correlations in Monozygotic Male (MZM) twin pairs (light green) and Monozygotic Female (MZF) twin pairs. The blue bars represent correlations in Dizygotic Male (DZM) twin pairs, Dizygotic Female (DZF) twin pairs and Dizygotic Opposite Sex (DOS) twin pairs. The green and blue bars reflect the correlations in a full model, while the orange bars reflect twin correlations for Dizygotic (DZ) twin pairs in the most parsimonious model, with: DZM (light orange), MZF (normal orange), DOS (dark orange).
Twin correlations for Brain and Cognition variables.The green bars represent correlations in Monozygotic Male (MZM) twin pairs (light green) and Monozygotic Female (MZF) twin pairs. The blue bars represent correlations in Dizygotic Male (DZM) twin pairs, Dizygotic Female (DZF) twin pairs and Dizygotic Opposite Sex (DOS) twin pairs. The green and blue bars reflect the correlations in a full model, while the orange bars reflect twin correlations for Dizygotic (DZ) twin pairs in the most parsimonious model, with: DZM (light orange), MZF (normal orange), DOS (dark orange).
Twin correlations for BMI and Height.1A: adult twins and 1B: adolescent twins. The green bars represent correlations in Monozygotic Male (MZM) twin pairs (light green) and Monozygotic Female (MZF) twin pairs. The blue bars represent correlations in Dizygotic Male (DZM) twin pairs, Dizygotic Female (DZF) twin pairs and Dizygotic Opposite Sex (DOS) twin pairs. The green and blue bars reflect the correlations in a full model, while the orange bars reflect twin correlations for Dizygotic (DZ) twin pairs in the most parsimonious model, with: DZM (light orange), MZF (normal orange), DOS (dark orange).
Twin correlations for Metabolic risk factors and Migraine.The green bars represent correlations in Monozygotic Male (MZM) twin pairs (light green) and Monozygotic Female (MZF) twin pairs. The blue bars represent correlations in Dizygotic Male (DZM) twin pairs, Dizygotic Female (DZF) twin pairs and Dizygotic Opposite Sex (DOS) twin pairs. The green and blue bars reflect the correlations in a full model, while the orange bars reflect twin correlations for Dizygotic (DZ) twin pairs in the most parsimonious model, with: DZM (light orange), MZF (normal orange), DOS (dark orange).
Summary of all observed correlations in opposite-sex twin (x-axis)pairs versus expected correlations correlations based on same-sex dizygotic twin correlations pairs(y-axis) for all 122 phenotypes included in the present paper.
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