A preliminary report on alcohol-associated DNA methylation and suicidal behavior: evidence using Mendelian randomization

Alcohol consumption, a risk factor for suicide, is associated with changes in DNA methylation, which may play a role in the pathophysiology of suicidality. Here, Mendelian randomization probes whether alcohol-associated changes in DNA methylation mediate risk for suicidal behavior. The results suggest that higher alcohol-associated DNA methylation levels at cg18120259 confer a weak causal effect. cg18120259 is instrumented by a cis-methylation quantitative trait locus (rs9472155) that is upstream of VEGFA and associated with circulating VEFG levels. To ascertain whether the cg18120259 finding is confounded by VEGF levels, a Mendelian randomization of VEGF levels on suicidality was performed, revealing a null effect. This implies circulating VEGF levels (observed among suicide attempters) may mark but not cause suicide. Both mechanisms should be re-examined in large replication studies, as the information might be harnessed for early detection of at-risk individuals and possibly save lives.