| Description |
Suicide is a serious public health problem. There is compelling evidence that genes account for some of the observed variability in suicidal behavior; despite this, molecular analyses have yielded highly inconsistent findings. Examining more phenotypically homogenous disease groups can yield greater power to detect genetic variants, suggesting that analysis of clinically meaningful subsets of suicide cases could be a valuable strategy in revealing hereditary contributions that may otherwise be obscured. Additionally, given the unique strengths and limitations of different genetic designs, convergent evidence across studies with different methodologies is needed. The present study includes two sets of related analyses, each aiming to identify different aspects of genetic risk for suicide in the context of personality pathology. For Study 1 that examined a more homogeneous subset of suicide cases we used the decedents linked to a pedigree characterized by statistically elevated risk for both personality disorders and suicide. Decedents in the high-risk pedigree were included in shared segment analyses. Several shared segments met criteria for suggestive significance. In Study 2, we compared genes captured within shared genetic segments to the extant literature to identify candidate genes of putative interest. Two genes, GPR52 and GCH1, were noted to be involved in dopaminergic neurotransmission, pathways that have been hypothesized to play a role in both suicide and personality pathology. Additionally, one gene, AUTS2, has demonstrated previous associations with suicidality. We used microarray DNA from iv a larger sample of mostly unrelated Utah suicide decedents to evaluate associations chosen candidate genes. Variants on all genes were associated with higher-than-expected minor allele frequency (MAF) in this larger sample of suicide cases. These results serve as an important proof-of-concept regarding the ways that multiple genetic approaches may be employed in search of convergent evidence of genes influencing disease risk. |
