Genome-Wide Association Study of Post-Traumatic Stress Disorder in Two High-Risk Populations

Abstract

Mexican Americans and American Indians constitute conspicuously understudied groups with respect to risk for post-traumatic stress disorder (PTSD), especially in light of findings showing racial/ethnic differences in trauma exposure and risk for PTSD. The purpose of this study was to examine genetic influences on PTSD in two minority cohorts. A genome-wide association study (GWAS) with sum PTSD symptoms for trauma-exposed subjects was run in each cohort. Six highly correlated variants in olfactory receptor family 11 subfamily L member 1 (OR11L1) were suggestively associated with PTSD in the Mexican American cohort. These associations remained suggestively significant after permutation testing. A signal in a nearby olfactory receptor on chromosome 1, olfactory receptor family 2 subfamily L member 13 (OR2L13), tagged by rs151319968, was nominally associated with PTSD in the American Indian sample. Although no variants were significantly associated after correction for multiple testing in a meta-analysis of the two cohorts, pathway analysis of the top hits showed an enrichment cluster of terms related to sensory transduction, olfactory receptor activity, G-protein coupled receptors, and membrane. As previous studies have proposed a role for olfaction in PTSD, our results indicate this influence may be partially driven by genetic variation in the olfactory system.

Prevalence of acute stress disorder among road traffic accident survivors: a meta-analysis

“…For example, it has been well-established that the profile of ASD symptoms varies greatly across cultures, especially with regard to the symptom cluster of dissociation [ 36 ]. Furthermore, the disparity of genetic background across ethnicities may have played a role in the different pooled prevalence observed across countries [ 37 ].…”

Recent Genetics and Epigenetics Approaches to PTSD

“…Most GWAS test hundreds of thousands to several million SNP variants, with the requirement that this large number of genetic features would need a large number of samples. Some of the current and most successful human GWAS in PTSD are summarized in Table 1, in which 11 genome-wide studies are reported in chronological order [12••, 39, 40, 41•, 42, 43•, 44•, 45•, 46•, 47, 48]. SNP identification numbers and nearest genes are also recorded together with the sample sizes and the ancestry breakdown.…”

“…In standard GWAS, the level of probability needed to reach “genome-wide significance” is simply the standard alpha = 0.05 divided by the approximate number of tests (~ 1,000,000 SNPs), for a derived multiple testing value of significance at p <5× 10 −8 . The majority of studies in Table 1 met genome-wide significance, except Wolf et al 2014, which was a GWAS focused on dissociation [42]; Kilaru et al [47], which used a different type of gene-based analysis, and thus arguably may not be required to meet the same GWAS level of statistical correction (since they were testing approximately 40,000 genes instead of 1 million SNPs); as well as Ashley-Koch et al [45] and Melroy-Greif et al [48]. …”

Spatial Epidemiology of Alcohol‐ and Drug‐Related Health Problems Among Northern Plains American Indians: Nebraska and South Dakota, 2007 to 2012

“…These conditions are not unlike those which have deprived minority Black populations of access to economic and social resources for many decades and multiple generations (Dymski & Mason, 2005). Although lifetime experiences of trauma and post-traumatic stress have been associated with behavioral health risks in Hispanic populations (Ehlers et al, 2016; Melroy-Greif, Wilhelmsen, Yehuda, & Ehlers, 2017), these effects are magnified and maintained–affectively and perhaps genetically–in populations for whom large-scale major traumas continue to be experienced across generations, as historical trauma (Ehlers, Gizer, Gilder, Ellingson, & Yehuda, 2013; Nutton & Fast, 2015; Soto, Baezconde-Garbanati, Schwartz, & Unger, 2015; Sule et al, 2017; Truesdale-Moore, 2017). Recent research links “historical trauma” to changes in DNA methylation (so-called epigenetic changes) (Aguiar & Halseth, 2013; Brockie, Heinzelmann, & Gill, 2013), although among American Indians and Alaska Natives this research may be limited by indigenous people’s understandable reluctance to provide tissue for such analyses (Lock, 2015).…”