Largest GWAS of PTSD (N=20 070) yields genetic overlap with schizophrenia and sex differences in heritability

Abstract

The Psychiatric Genomics Consortium-Posttraumatic Stress Disorder group (PGC-PTSD) combined genome-wide case–control molecular genetic data across 11 multiethnic studies to quantify PTSD heritability, to examine potential shared genetic risk with schizophrenia, bipolar disorder, and major depressive disorder and to identify risk loci for PTSD. Examining 20 730 individuals, we report a molecular genetics-based heritability estimate (h2SNP) for European-American females of 29% that is similar to h2SNP for schizophrenia and is substantially higher than h2SNP in European-American males (estimate not distinguishable from zero). We found strong evidence of overlapping genetic risk between PTSD and schizophrenia along with more modest evidence of overlap with bipolar and major depressive disorder. No single-nucleotide polymorphisms (SNPs) exceeded genome-wide significance in the transethnic (overall) meta-analysis and we do not replicate previously reported associations. Still, SNP-level summary statistics made available here afford the best-available molecular genetic index of PTSD—for both European- and African-American individuals—and can be used in polygenic risk prediction and genetic correlation studies of diverse phenotypes. Publication of summary statistics for ∼10 000 African Americans contributes to the broader goal of increased ancestral diversity in genomic data resources. In sum, the results demonstrate genetic influences on the development of PTSD, identify shared genetic risk between PTSD and other psychiatric disorders and highlight the importance of multiethnic/racial samples. As has been the case with schizophrenia and other complex genetic disorders, larger sample sizes are needed to identify specific risk loci.

Exploring the association of genetic factors with participation in the Avon Longitudinal Study of Parents and Children

“…rs406001) were identified in a previous GWAS of post-traumatic stress disorder (PTSD), but not replicated in the original GWAS 40 . Furthermore, this locus was only nominally associated with PTSD in a much larger GWAS 41 . This, coupled with the low minor allele frequency of SNPs in the genome-wide significant locus in our GWAS, suggests that this may be a chance finding, rather than an effect of PTSD on participation.…”

The Effects of a <b><i>BDNF</i></b> Val66Met Polymorphism on Posttraumatic Stress Disorder: A Meta-Analysis

“…Sex has been shown to influence the likelihood of a PTSD diagnosis, and preliminary work suggested that these genetic influences were stronger in women than men [29]. However, other works on BDNF by sex interactions to predict related phenotypes have mixed results [46, 47].…”

“…However, a major limitation in the extant literature is that potential ethnicity and sex differences were not examined. Examination of sex effects is critical, considering the finding that PTSD may be more genetically driven in females [29]. To illustrate, preliminary evidence has shown that estrogen induces the synthesis of BDNF in several brain regions [30], which could contribute to an elevated risk for PTSD in females versus males.…”

Letter to the Editor: Posttraumatic stress disorder has genetic overlap with cardiometabolic traits

“…The Psychiatric Genomics Consortium (PGC)-PTSD working group has been leading efforts to identify genetic risk variants associated with PTSD (Logue et al , 2015), and the first meta-analysis of PTSD GWASs ( N =20,070) has been recently completed by this group (Duncan et al , 2017). In the present study, we used summary statistics from the PGC-PTSD meta-analysis of Duncan and colleagues (2017) to conduct the first GWAS-based investigation of potential genetic overlap between PTSD and cardiometabolic traits.…”

“…In the present study, we used summary statistics from the PGC-PTSD meta-analysis of Duncan and colleagues (2017) to conduct the first GWAS-based investigation of potential genetic overlap between PTSD and cardiometabolic traits.…”