14 research outputs found
Fine Mapping on Chromosome 13q32â34 and Brain Expression Analysis Implicates MYO16 in Schizophrenia
We previously reported linkage of schizophrenia and schizoaffective disorder to 13q32â34 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 13q32â34
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 caseâcontrol 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 within
MYO16 in a second set of Afrikaner families and additional caseâcontrol data sets of European descent highlighted a region across introns
2â6 as the most likely region to harbor common MYO16 risk variants. Expression analysis revealed a significant increase in the level of
MYO16 expression in the brains of schizophrenia patients. Our results suggest that common variation within MYO16 may contribute to
the genetic liability to schizophrenia.National Institute of Mental Health (NIMH) Grant MH061399, the Lieber Center for Schizophrenia Research at Columbia University, Gray Matters Fellowship and NARSAD Young Investigator Award.http://www.nature.com/npphb201