HLA-B Maternal-Fetal Genotype Matching Increases Risk of Schizophrenia

• Published in: American journal of human genetics Vol. 79; no. 4; pp. 710 - 715
• Main Authors: Palmer, Christina G.S., Hsieh, Hsin-Ju, Reed, Elaine F., Lonnqvist, Jouko, Peltonen, Leena, Woodward, J. Arthur, Sinsheimer, Janet S.
• Format: Journal Article
• Language: English
• Published: Chicago, IL Elsevier Inc 01-10-2006; University of Chicago Press; Cell Press; The American Society of Human Genetics
• Subjects: Antigens; Biological and medical sciences; Female; Genealogy; General aspects. Genetic counseling; Genotype; Genotype & phenotype; HLA Antigens - immunology; HLA-A Antigens - genetics; HLA-B Antigens - genetics; HLA-DR Antigens - genetics; HLA-DRB1 Chains; Humans; Leukocytes; Male; Medical genetics; Medical sciences; Nuclear Family; Pregnancy; Pregnancy Complications - genetics; Pregnancy Complications - immunology; Prenatal care; Risk Factors; Schizophrenia; Schizophrenia - genetics; Schizophrenia - physiopathology; Sex Characteristics; Human; HLA-System; Typing; Major histocompatibility system; Schizophrenia; Genotype; Risk; Increase; Psychosis; Microbiological investigation; Mother; Risk factor; Fetus; Genetics; Class I histocompatibility antigen
• ISSN: 0002-9297; 1537-6605
• DOI: 10.1086/507829

Schizophrenia and human leukocyte antigen (HLA) matching between couples or between mothers and offspring have independently been associated with prenatal/obstetric complications, including preeclampsia and low birth weight. Here, we report the results of a family-based candidate-gene study that brings together these two disparate lines of research by assessing maternal-fetal genotype matching at HLA-A, -B, and -DRB1 as a risk factor of schizophrenia. We used a conditional-likelihood modeling approach with a sample of 274 families that had at least one offspring with schizophrenia or a related spectrum disorder. A statistically significant HLA-B maternal-fetal genotype–matching effect on schizophrenia was demonstrated for female offspring (
P=.01; parameter estimate 1.7 [95% confidence interval 1.22–2.49]). Because the matching effect could be associated with pregnancy complications rather than with schizophrenia per se, these findings are consistent with the neurodevelopmental hypothesis of schizophrenia and with accumulating evidence that the prenatal period is involved in the origins of this disease. Our approach demonstrates how genetic markers can be used to characterize the biology of prenatal risk factors of schizophrenia.