| Abstract |
We previously reported linkage ofschizophreniaand schizoaffective disorder to 13q32-34 in the European descent Afrikaner population from South Africa. The nature of genetic variation underlying linkage peaks in psychiatric disorders remains largely unknown and both rare and common variants may be contributing. Here, we examine the contribution of common variants located under the 13q32-34 linkage region. We used densely spaced SNPs to fine map the linkage peak region using both a discovery sample of 415 families and a meta-analysis incorporating two additional replication family samples. In a second phase of the study, we use one family-based data set with 237 families and independent case-control data sets for fine mapping of the common variant association signal using HapMap SNPs. We report a significant association with a genetic variant (rs9583277) within the gene encoding for the myosin heavy-chain Myr 8 (MYO16), which has been implicated in neuronal phosphoinositide 3-kinase signaling. Follow-up analysis of HapMap variation withinMYO16第二组的南非白人家庭和additional case-control data sets of European descent highlighted a region across introns 2-6 as the most likely region to harbor commonMYO16risk variants. Expression analysis revealed a significant increase in the level ofMYO16expression in the brains ofschizophreniapatients. Our results suggest that common variation withinMYO16may contribute to the genetic liability toschizophrenia. |