title: Effect of Rhesus D incompatibility on schizophrenia depends on offspring sex.
abstract: Rhesus D incompatibility increases risk for schizophrenia, with some evidence that risk is limited to male offspring. The purpose of this study is to determine whether risk for schizophrenia due to Rhesus D incompatibility differs by offspring sex using a nuclear family-based candidate gene approach and a meta-analysis approach. The genetic study is based on a sample of 277 nuclear families with RHD genotype data on at least one parent and at least one child diagnosed with schizophrenia or related disorder. Meta-analysis inclusion criteria were (1) well-defined sample of schizophrenia patients with majority born before 1970, (2) Rhesus D incompatibility phenotype or genotype data available on mother and offspring, and by offspring sex. Two of ten studies, plus the current genetic study sample, fulfilled these criteria, for a total of 358 affected males and 226 affected females. The genetic study found that schizophrenia risk for incompatible males was significantly greater than for compatible offspring (p=0.03), while risk for incompatible and compatible females was not significantly different (p=.32). Relative risks for incompatible males and females were not significantly different from each other. Meta-analysis using a larger number of affected males and females supports their difference. Taken together, these results provide further support that risk of schizophrenia due to Rhesus D incompatibility is limited to incompatible males, although a weak female incompatibility effect cannot be excluded. Sex differences during fetal neurodevelopment should be investigated to fully elucidate the etiology of schizophrenia.
authors.affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA, 90095, USA. cpalmer@mednet.ucla.edu
authors.forename: Christina G S
authors.initials: CG
authors.lastname: Palmer
authors.forename: Erin
authors.initials: E
authors.lastname: Mallery
authors.forename: Joni A
authors.initials: JA
authors.lastname: Turunen
authors.forename: Hsin-Ju
authors.initials: HJ
authors.lastname: Hsieh
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Jouko
authors.initials: J
authors.lastname: Lonnqvist
authors.forename: J Arthur
authors.initials: JA
authors.lastname: Woodward
authors.forename: Janet S
authors.initials: JS
authors.lastname: Sinsheimer
mesh_terms: D005260:Female; D005315:Fetal Diseases / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D005820:Genetic Testing; D005838:Genotype; D006801:Humans; D008297:Male; D009035:Mothers; D010641:Phenotype; D011247:Pregnancy; D012204:Rh-Hr Blood-Group System / Q000235:genetics*; D012559:Schizophrenia; D035781:Siblings
chemical_list: D012204:Rh-Hr Blood-Group System; C026410:Rho(D) antigen