HLA-B maternal-fetal genotype matching increases risk of schizophrenia.
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.
Palmer
Christina G S
CG
Department of Psychiatry and Biobehavioral Sciences, University of California-Los Angeles, Los Angeles, CA 90095, USA. cpalmer@mednet.ucla.edu
Hsieh
Hsin-Ju
HJ
Reed
Elaine F
EF
Lonnqvist
Jouko
J
Peltonen
Leena
L
Woodward
J Arthur
JA
Sinsheimer
Janet S
JS
D005260:Female; D005838:Genotype; D006680:HLA Antigens / Q000276:immunology; D015234:HLA-A Antigens / Q000235:genetics; D015235:HLA-B Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D009679:Nuclear Family; D011247:Pregnancy; D011248:Pregnancy Complications / Q000235:genetics / Q000276:immunology; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000503:physiopathology; D012727:Sex Characteristics
D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains