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.
Recent adaptive selection at MAOB and ancestral susceptibility to schizophrenia†
Version of Record online: 13 JUN 2008
Copyright © 2008 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 150B, Issue 3, pages 369–374, 5 April 2009
How to Cite
Carrera, N., Sanjuán, J., Moltó, M. D., Carracedo, Á. and Costas, J. (2009), Recent adaptive selection at MAOB and ancestral susceptibility to schizophrenia. Am. J. Med. Genet., 150B: 369–374. doi: 10.1002/ajmg.b.30823
- Issue online: 17 MAR 2009
- Version of Record online: 13 JUN 2008
- Manuscript Accepted: 28 MAY 2008
- Manuscript Received: 6 MAR 2008
- Ministerio de Sanidad y Consumo, Spain. Grant Numbers: PI052036, FIS 02/0018
- dopaminergic hypothesis;
- case–control studies;
- monoamine oxidase;
- natural selection;
- common disease-common variant hypothesis
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.