title: Sex-specific differences in effect size estimates at established complex trait loci.
abstract: BACKGROUND
  Genetic differences between men and women may contribute to sex differences in prevalence and progression of many common complex diseases. Using the WTCCC GWAS, we analysed whether there are sex-specific differences in effect size estimates at 142 established loci for seven complex diseases: rheumatoid arthritis, type 1 diabetes (T1D), Crohn's disease, type 2 diabetes (T2D), hypertension, coronary artery disease and bipolar disorder.
  
  
  METHODS
  For each Single nucleotide polymorphism (SNP), we calculated the per-allele odds ratio for each sex and the relative odds ratios (RORs; the effect size is higher in men with ROR greater than one). RORs were then meta-analysed across loci within each disease and across diseases.
  
  
  RESULTS
  For each disease, summary RORs were not different from one, but there was between-SNP heterogeneity in the RORs for T1D and T2D. Four loci in T1D, three in Crohn's disease and three in T2D showed differences in the genetic effect between men and women (P<0.05). We probed these differences in additional independent replication samples for T1D and T2D. The differences remained for the T1D loci CTSH, 17q21 and 20p13 and the T2D locus BCL11A, when WTCCC data and replication data were meta-analysed. Only CTSH showed different genetic effect between men and women in the replication data alone.
  
  
  CONCLUSIONS
  Our results exclude the presence of large and frequent differences in the effect size estimates between men and women for the established loci in the seven common diseases explored. Documenting small differences in genetic effects between men and women requires large studies and systematic evaluation.
authors: Arthritis Research UK Epidemiology Unit, Manchester Academic Health Science Centre, The University of Manchester, UK. gisela.orozco@manchester.ac.uk
authors: Gisela
authors: G
authors: Orozco
authors: John P A
authors: JP
authors: Ioannidis
authors: Andrew
authors: A
authors: Morris
authors: Eleftheria
authors: E
authors: Zeggini
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics; D001714:Bipolar Disorder / Q000235:genetics; D002908:Chronic Disease / Q000453:epidemiology*; D003324:Coronary Artery Disease / Q000235:genetics; D003424:Crohn Disease / Q000235:genetics; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D006973:Hypertension / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012727:Sex Characteristics; D012737:Sex Factors