Translational Psychiatry has accepted for publication our paper "Genetic Risk Factors in two Utah Pedigrees at High Risk for Suicide." First author Hilary Coon, Ph.D. will be presenting this paper as a poster at ASHG 2013 in Boston.

We used unique population-based data resources to identify 22 high-risk extended pedigrees that show clustering of suicide twice to three times that expected from age-sex-cohort adjusted incidence rates that also incorporate pedigree structure. We have studied genetic risk factors in 5 of these large pedigrees each with 17-51 related suicide decedents, 5-9 of which have previously-collected DNA. These decedents were genotyped with the Illumina HumanExome BeadChip. Genotypes were analyzed using the Variant Annotation, Analysis, and Search (VAAST) program package that computes likelihoods of risk variants using the functional impact of the DNA variation, aggregative scoring of multiple variants across each gene, and pedigree structure. We prioritized variants that were: 1) shared across pedigree members, 2) rare in publicly-available sequence data from 1,358 controls, and 3) screened against 258 other Utah suicides not in the pedigrees to eliminate potential false positives. Sequence variants were prioritized statistically and then implicated genes were screened for previous disease associations and functional relevance. Findings included membrane protein genes and several genes with neuronal involvement and/or known associations with psychiatric conditions. Genes implicated in particular pedigrees may be associated with significant co-morbid psychiatric or medical conditions and/or demographic attributes unique to that pedigree. While the study is limited to variants included on the HumanExome BeadChip, these findings warrant further exploration, and demonstrate the utility of this high-risk pedigree resource.