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Recent adaptive selection at MAOB and ancestral susceptibility to schizophrenia

Authors

  • Noa Carrera,

    1. Fundación Pública Galega de Medicina Xenómica (FPGMX), University of Santiago Hospital Complex, Santiago de Compostela, Spain
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  • Julio Sanjuán,

    1. Psychiatric Unit, Valencia Medical School, CIBERSAM, Valencia, Spain
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  • María Dolores Moltó,

    1. Faculty of Biology, Genetic Department, Valencia University, Valencia, Spain
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  • Ángel Carracedo,

    1. Fundación Pública Galega de Medicina Xenómica (FPGMX), University of Santiago Hospital Complex, Santiago de Compostela, Spain
    2. Genomic Medicine Group, Institute of Legal Medicine, University of Santiago de Compostela, Centro Nacional de Genotipado (CeGen), CIBERER, Santiago de Compostela, Spain
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  • Javier Costas

    Corresponding author
    1. Fundación Pública Galega de Medicina Xenómica (FPGMX), University of Santiago Hospital Complex, Santiago de Compostela, Spain
    • Fundación Pública Galega de Medicina Xenómica-SERGAS, Hospital Clínico Universitario de Santiago, Edif. Consultas Planta-2, E-15706 Santiago de Compostela, Spain.
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  • Please cite this article as follows: Carrera N, Sanjuán J, Moltó MD, Carracedo Á, Costas J. 2009. Recent Adaptive Selection at MAOB and Ancestral Susceptibility to Schizophrenia. Am J Med Genet Part B 150B:369–374.

Abstract

The ancestral susceptibility hypothesis has been proposed to explain the existence of susceptibility alleles to common diseases. Some ancestral alleles, reflecting ancient adaptations, may be poorly adapted to the more contemporary environmental conditions giving rise to an increased risk to suffer some common disorders. In order to test this hypothesis in schizophrenia, we focused on the monoamine oxidase B gene (MAOB). This gene is involved in deamination of several monoamines, including both xenobiotic amines present in several foods, as well as neurotransmitters such as dopamine. In addition, preliminary analysis based on phase I HapMap data suggested that recent natural selection has acted on this locus. We further explored the existence of this recent positive selection using a test based on extension of linkage disequilibrium (LD) to large distance at the specific selected haplotype taking data from HapMap phase II, and searched for association of the ancestral haplotypes with schizophrenia in a sample of 532 schizophrenic patients and 597 controls from Spain. Our analysis suggested the existence of a haplotype of MAOB subject to recent selection. In agreement with the ancestral susceptibility hypothesis, the ancestral haplotypes were significantly over-represented in patients (P = 0.047). These haplotypes conferred an increased risk to schizophrenia, restricted to males (P = 0.024, OR = 1.41, 95% CI 1.01–1.90). Thus, pending on replication studies, MAOB seems to fit the ancestral susceptibility model, validating a new strategy to search for common schizophrenia susceptibility genes by focusing in those functional candidate genes subject to recent positive selection. © 2008 Wiley-Liss, Inc.

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