Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036341 (schizophrenia)
 60,220 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fetal events and obstetric complications are associated with schizophrenia. Here we report the results of a family-based candidate-gene study that assesses the role of maternal-fetal genotype incompatibility at the RHD locus in schizophrenia. We adapted the case-parent-trio log-linear modeling approach to test for RHD maternal-fetal genotype incompatibility and to distinguish this effect from a high-risk allele at or near the RHD locus and from a direct maternal effect alone. Eighty-eight patient-parent trios, 72 patient-mother pairs, and 21 patient-father pairs were genotyped at the RHD locus. Of the 181 patients, 62% were male and 81% were second born or later. Only three patients were born after prophylaxis against maternal isoimmunization had become common practice. There was significant evidence for an RHD maternal-fetal genotype incompatibility, and the incompatibility parameter was estimated at 2.6. There was no evidence to support linkage/association with schizophrenia at or near the RHD locus nor any evidence to support the role of maternal genotype effect alone. Our results replicate previous findings that implicate the RHD locus in schizophrenia, and the candidate-gene design of this study allows the elimination of alternative explanations for the role of this locus in disease. Thus, the present study provides increasing evidence that the RHD locus increases schizophrenia risk through a maternal-fetal genotype incompatibility mechanism that increases risk of an adverse prenatal environment (e.g., Rh incompatibility) rather than through linkage/association with the disorder, linkage disequilibrium with an unknown nearby susceptibility locus, or a direct maternal effect alone. This is the first candidate-gene study to explicitly test for and provide evidence of a maternal-fetal genotype incompatibility mechanism in schizophrenia.
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PMID:RHD maternal-fetal genotype incompatibility increases schizophrenia susceptibility. 1243 25

Rh incompatibility disease (ie Rh hemolytic disease of the fetus and newborn) has been implicated as a risk factor for schizophrenia. Here, we extend the maternal-fetal genotype incompatibility (MFG) test used in an earlier case-parent trio study that found significant evidence for an increased risk of schizophrenia in RHD MFG-incompatible children. We modify the MFG test for case-parent trios to include any number of siblings. This modified test enables us to use more of the available data from the earlier study. The increased sample size not only gives us greater power to test for MFG incompatibility but it also enables us to model the impact of previous RHD MFG-incompatible pregnancies on the relative risk of RHD MFG incompatibility in later-born siblings. This modeling is important, because RHD MFG incompatibility is a proxy for Rh incompatibility disease, and the risk of Rh incompatibility disease increases with the number of previous RHD MFG-incompatible pregnancies. The best-fitting models are consistent with the hypothesized effect that previous incompatible pregnancies increase the risk of schizophrenia due to RHD MFG incompatibility. There was significant evidence that the relative risk of schizophrenia in the second- and later-born RHD MFG-incompatible children is 1.7, consistent with earlier estimates. Our extension of the MFG test has general application to family-based studies of maternal-genotype and MFG interaction effects.
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PMID:RHD maternal-fetal genotype incompatibility and schizophrenia: extending the MFG test to include multiple siblings and birth order. 1473 56

Evidence is presented that RHD, RHCE, and other RH genes, may be interesting candidates to consider when searching for the genetic basis of hair whorl rotation (i.e., clockwise or counterclockwise), handedness (i.e., right handed, left handed or ambidextrous), speech laterality (i.e., right brained or left brained), speech dyslexia (e.g., stuttering), sexual orientation (i.e., heterosexual, homosexual, bisexual, or transsexual), schizophrenia, bipolar disorder, and autism spectrum disorder. Such evidence involves the need for a genetic model that includes maternal immunization to explain some of the empirical results reported in the literature. The complex polymorphisms present among the maternally immunizing RH genes can then be used to explain other empirical results. Easily tested hypotheses are suggested, based upon genotypic (but not phenotypic) frequencies of the RH genes. In particular, homozygous dominant individuals are expected to be less common or lacking entirely among the alternative phenotypes. If it is proven that RH genes are involved in brain architecture, it will have a profound effect upon our understanding of the development and organization of the asymmetrical vertebrate brain and may eventually lead to a better understanding of the developmental processes which occur to produce the various alternative phenotypes discussed here. In addition, if RH genes are shown to be involved in the production of these phenotypes, then the evolutionary studies can be performed to demonstrate the beneficial effect of the recessive alleles of RHD and RHCE, and why human evolution appears to be selecting for the recessive alleles even though an increase in the frequency of such alleles may imply lower average fecundity among some individuals possessing them.
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PMID:The genetic basis of hair whorl, handedness, and other phenotypes. 1633 93

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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PMID:Effect of Rhesus D incompatibility on schizophrenia depends on offspring sex. 1869 92

Prenatal/obstetric complications are implicated in schizophrenia susceptibility. Some complications may arise from maternal-fetal genotype incompatibility, a term used to describe maternal-fetal genotype combinations that produce an adverse prenatal environment. A review of maternal-fetal genotype incompatibility studies suggests that schizophrenia susceptibility is increased by maternal-fetal genotype combinations at the RHD and HLA-B loci. Maternal-fetal genotype combinations at these loci are hypothesized to have an effect on the maternal immune system during pregnancy which can affect fetal neurodevelopment and increase schizophrenia susceptibility. This article reviews maternal-fetal genotype incompatibility studies and schizophrenia and discusses the hypothesized biological role of these ''incompatibility genes". It concludes that research is needed to further elucidate the role of RHD and HLA-B maternal-fetal genotype incompatibility in schizophrenia and to identify other genes that produce an adverse prenatal environment through a maternal-fetal genotype incompatibility mechanism. Efforts to develop more sophisticated study designs and data analysis techniques for modeling maternal-fetal genotype incompatibility effects are warranted.
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PMID:Evidence for maternal-fetal genotype incompatibility as a risk factor for schizophrenia. 2037 78