Melroy-Greif Whitney E, Wilhelmsen Kirk C, Yehuda Rachel, Ehlers Cindy L
Department of Neuroscience,The Scripps Research Institute,La Jolla,CA,USA.
Department of Genetics and Neurology,University of North Carolina,Chapel Hill,NC,USA.
Twin Res Hum Genet. 2017 Jun;20(3):197-207. doi: 10.1017/thg.2017.12. Epub 2017 Mar 6.
Mexican Americans (MAs) and American Indians (AIs) 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 MA 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 AI 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.
墨西哥裔美国人(MAs)和美国印第安人(AIs)是创伤后应激障碍(PTSD)风险方面明显未得到充分研究的群体,尤其是鉴于研究结果显示在创伤暴露和PTSD风险方面存在种族/民族差异。本研究的目的是检验两个少数群体队列中基因对PTSD的影响。在每个队列中,对遭受创伤的受试者进行了一项全基因组关联研究(GWAS),以汇总PTSD症状。嗅觉受体家族11亚家族L成员1(OR11L1)中的六个高度相关变体在MA队列中与PTSD存在提示性关联。经过置换检验后,这些关联仍然具有提示性显著意义。在1号染色体上附近的一个嗅觉受体,即嗅觉受体家族2亚家族L成员13(OR2L13)中,由rs151319968标记的一个信号在AI样本中与PTSD存在名义上的关联。尽管在对两个队列进行的荟萃分析中,经过多重检验校正后没有变体显著相关,但对顶级命中结果的通路分析显示,与感觉转导、嗅觉受体活性、G蛋白偶联受体和膜相关的术语富集聚类。由于先前的研究提出嗅觉在PTSD中起作用,我们的结果表明这种影响可能部分由嗅觉系统的基因变异驱动。
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