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Effect of Rhesus D incompatibility on schizophrenia depends on offspring sex.

Palmer CG, Mallery E, Turunen JA, Hsieh HJ, Peltonen L, Lonnqvist J, Woodward JA, Sinsheimer JS - Schizophr. Res. (2008)

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA, 90095, USA. cpalmer@mednet.ucla.edu

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.

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Individual study and pooled sex-specific estimates of Rhesus D incompatibility relative risk for schizophrenia. Filled symbols denote estimates for incompatible males; open symbols denote estimates for incompatible females. Diamond=estimate derived from meta-analysis; Triangle=estimate derived from data published in Hollister et al. (1996); Square=estimate derived from data published in Insel et al. (2005); Circle=estimate derived from current candidate gene study. Solid vertical line denotes  value and dashed vertical line denotes meta-analysis estimate for incompatible males.
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Figure 1: Individual study and pooled sex-specific estimates of Rhesus D incompatibility relative risk for schizophrenia. Filled symbols denote estimates for incompatible males; open symbols denote estimates for incompatible females. Diamond=estimate derived from meta-analysis; Triangle=estimate derived from data published in Hollister et al. (1996); Square=estimate derived from data published in Insel et al. (2005); Circle=estimate derived from current candidate gene study. Solid vertical line denotes value and dashed vertical line denotes meta-analysis estimate for incompatible males.

Mentions: We then performed a meta-analysis of three studies to estimate sex-specific Rhesus D incompatibility risks for schizophrenia. There was no evidence of heterogeneity across the three studies (Q statistic for male offspring data=2.07, p=0.356; Q statistic for female offspring data=0.485, p=0.785) indicating that pooling their results is justified (Fleiss, 1993). The pooled estimate of μmale=1.64 with 90% CI 1.25–2.17 and the pooled estimate of μfemale=1.07, with 90% CI 0.72–1.58. The 90% CI for μmale does not cover the value of one, supporting an incompatibility effect in male offspring; while the 90% CI for μfemale includes the value, providing additional support for an incompatibility effect that is limited to male offspring. Fig. 1 displays the study-specific estimates of μmale, μfemale, and their upper and lower 90% CI values. In each individual study μmale > μfemale which is consistent with the results of the meta-analysis.


Effect of Rhesus D incompatibility on schizophrenia depends on offspring sex.

Palmer CG, Mallery E, Turunen JA, Hsieh HJ, Peltonen L, Lonnqvist J, Woodward JA, Sinsheimer JS - Schizophr. Res. (2008)

Individual study and pooled sex-specific estimates of Rhesus D incompatibility relative risk for schizophrenia. Filled symbols denote estimates for incompatible males; open symbols denote estimates for incompatible females. Diamond=estimate derived from meta-analysis; Triangle=estimate derived from data published in Hollister et al. (1996); Square=estimate derived from data published in Insel et al. (2005); Circle=estimate derived from current candidate gene study. Solid vertical line denotes  value and dashed vertical line denotes meta-analysis estimate for incompatible males.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2572267&req=5

Figure 1: Individual study and pooled sex-specific estimates of Rhesus D incompatibility relative risk for schizophrenia. Filled symbols denote estimates for incompatible males; open symbols denote estimates for incompatible females. Diamond=estimate derived from meta-analysis; Triangle=estimate derived from data published in Hollister et al. (1996); Square=estimate derived from data published in Insel et al. (2005); Circle=estimate derived from current candidate gene study. Solid vertical line denotes value and dashed vertical line denotes meta-analysis estimate for incompatible males.
Mentions: We then performed a meta-analysis of three studies to estimate sex-specific Rhesus D incompatibility risks for schizophrenia. There was no evidence of heterogeneity across the three studies (Q statistic for male offspring data=2.07, p=0.356; Q statistic for female offspring data=0.485, p=0.785) indicating that pooling their results is justified (Fleiss, 1993). The pooled estimate of μmale=1.64 with 90% CI 1.25–2.17 and the pooled estimate of μfemale=1.07, with 90% CI 0.72–1.58. The 90% CI for μmale does not cover the value of one, supporting an incompatibility effect in male offspring; while the 90% CI for μfemale includes the value, providing additional support for an incompatibility effect that is limited to male offspring. Fig. 1 displays the study-specific estimates of μmale, μfemale, and their upper and lower 90% CI values. In each individual study μmale > μfemale which is consistent with the results of the meta-analysis.

Bottom Line: 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.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.

View Article: PubMed Central - PubMed

Affiliation: Department of Psychiatry & Biobehavioral Sciences, University of California, Los Angeles, CA, 90095, USA. cpalmer@mednet.ucla.edu

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.

Show MeSH
Related in: MedlinePlus