Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers.
Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers.
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DOI：
10.1001/jamapsychiatry.2016.0350
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发表时间：
2016-07-01
期刊：
影响因子：
25.8
通讯作者：
Army Study to Assess Risk and Resilience in Servicemembers (STARRS) Collaborators
中科院分区：
文献类型：
--
作者：
Stein MB;Chen CY;Ursano RJ;Cai T;Gelernter J;Heeringa SG;Jain S;Jensen KP;Maihofer AX;Mitchell C;Nievergelt CM;Nock MK;Neale BM;Polimanti R;Ripke S;Sun X;Thomas ML;Wang Q;Ware EB;Borja S;Kessler RC;Smoller JW;Army Study to Assess Risk and Resilience in Servicemembers (STARRS) Collaborators
创伤后应激障碍(PTSD)是一种普遍而严重的公共卫生问题，尤其是在军队中。确定创伤后应激障碍的遗传危险因素可能会对易感性和共病的生物学基础提供重要的见解。在陆军研究的两个队列中发现与终生创伤后应激障碍风险相关的遗传基因，以评估军人的风险和弹性(陆军STARR)。两项关于美国军队心理健康的协调全基因组关联研究：新士兵研究(NSS，N=3167例和4607名创伤暴露对照)和部署前/部署后研究(PPD，N=947例和4969名创伤暴露对照)。初步分析比较了终生DSM-IV创伤后应激障碍患者与无终生创伤后应激障碍的创伤暴露对照组。采用Logistic回归模型对3个祖先群体(欧洲人、非洲人、拉丁人)进行关联分析，然后进行Meta分析。对遗传度和遗传相关性以及与其他精神和免疫相关疾病的多效性进行了估计。我们在5号染色体上的ANKRD55中观察到一个全基因组显著的基因座(rs159572；优势比[OR]=1.62，p值=2.43×10−8；调整后的累积创伤暴露[aOR]=1.68，p值=1.18×10−8)。我们还在19号染色体上的ZNF626(rs11085374；OR=0.77，p值=4.59×10−8)上观察到了一个全基因组显著的基因座。我们没有在PPDS样本的相应祖先组中发现类似的结果，也没有在其他祖先组或跨祖先荟萃分析中发现类似的结果。基于SNP的遗传力不显著，PTSD与6种精神障碍和9种免疫相关疾病之间没有显著的遗传相关性。在创伤后应激障碍和类风湿性关节炎之间观察到了显著的多效性证据，在较小程度上也观察到牛皮癣。在迄今为止最大规模的创伤后应激障碍GWA中，涉及美国军队样本，我们发现了有限的与特定基因座相关的证据。需要进一步努力在全基因组范围内复制与ANKRD55的显著关联--在先前的研究中，ANKRD55与几种自身免疫性和炎症性疾病有关--并澄清PTSD与类风湿性关节炎和牛皮癣之间观察到的基因重叠的性质。
Posttraumatic stress disorder (PTSD) is a prevalent, serious public health concern, particularly in the military. The identification of genetic risk factors for PTSD may provide important insights into the biological basis of vulnerability and comorbidity. To discover genetic loci associated with lifetime PTSD risk in two cohorts from the Army Study To Assess Risk and Resilience in Servicemembers (Army STARRS). Two coordinated genomewide association studies of mental health in the US military: New Soldier Study (NSS, N=3167 cases and 4607 trauma-exposed controls) and Pre/Post Deployment Study (PPDS, N=947 cases and 4969 trauma-exposed controls). The primary analysis compared lifetime DSM-IV PTSD cases to trauma-exposed controls without lifetime PTSD. Association analyses were conducted for PTSD using logistic regression models within each of 3 ancestral groups (European, African, Latino) by study and then meta-analyzed. Heritability and genetic correlation and pleiotropy with other psychiatric and immune-related disorders were estimated. We observed a genomewide significant locus in ANKRD55 on chromosome 5 (rs159572; odds ratio [OR] = 1.62, p-value =2.43×10−8; adjusted for cumulative trauma exposure [AOR] = 1.68, p-value = 1.18×10−8) in the African American samples from NSS. We also observed a genomewide significant locus in or near ZNF626 on chromosome 19 (rs11085374; OR = 0.77, p-value = 4.59 ×10−8) in the European American samples from NSS. We did not find similar results for either SNP in the corresponding ancestry group from the PPDS sample, or in other ancestral groups or trans-ancestral meta-analyses. SNP-based heritability was non-significant, and no significant genetic correlations were observed between PTSD and six mental disorders and nine immune-related disorders. Significant evidence of pleiotropy was observed between PTSD and rheumatoid arthritis and, to a lesser extent, psoriasis. In the largest GWAS of PTSD to date, involving a US military sample, we found limited evidence of association for specific loci. Further efforts are needed to replicate the genomewide significant association with ANKRD55 – associated in prior research with several autoimmune and inflammatory disorders – and to clarify the nature of the genetic overlap observed between PTSD and rheumatoid arthritis and psoriasis.