Abstract
Background Heritability of suicide risk is estimated at 43%, thus genetic risk likely plays an important role in completion of suicide. Previous genetic research has focused primarily on suicidal behavior or ideation rather than actual completed suicide. And previous genome-wide association studies of completion of suicide have been very small due to the difficulty in obtaining suicide sample data, and have been unable to identify genome-wide significant variants, likely due to power limitations. This study presents results from the first wave of a large Utah sample of completed suicides, and represent the most statistically powerful sample of completed suicide to date.
Methods Tissue samples from 1321 decedents were collected via partnership with the Utah Office of the Medical Examiner and genotyped using the Illumina Infinium PsychArray platform. Bioconductor package RaMWAS (A.S.) was used on post-QC hard call data (271,894 common variants) to conduct GWAS. Because the sample is from Utah, the authors were able to conduct a relatively direct comparison with 1000 Genomes controls also from Utah (CEU), as well as European controls (EUR). The first GWAS with Utah CEU controls (n of only 99) was followed by a second GWAS with EUR controls (n = 503) with and without CEU included in the control sample.
Results Analyses identified 8 SNPs in 6 genes associated with the completion of suicide. Six SNPs met genome-wide significance. Two of these variant hits were replicated using EUR controls not including the CEU sample, though the case sample was the same in both analyses. Subsequent QC steps (linkage disequilibrium analysis and EUR GWAS replication) further substantiated significant results implicating cytochrome P450 genes.
Conclusions This GWAS and partial replication of findings across control samples, using hard call genotype data, represents a significant step toward understanding the genetic architecture of suicide. These are late-breaking results, and in January this group will follow up with analyses using the full 2 waves (N = 4800 cases), a larger control group, and imputed data to ~11 million variants. Analyses to date implicate cytochrome P450 sites involved in metabolism of arachidonic acid and related inflammatory mediators. Results implicate inflammation in suicide risk, and add to a growing body of evidence that lung function may be tied to suicide.