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Genome-wide analyses of psychological resilience in U.S. Army soldiers.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics ( IF 2.8 ) Pub Date : 2019-05-13 , DOI: 10.1002/ajmg.b.32730
Murray B Stein 1, 2, 3 , Karmel W Choi 4 , Sonia Jain 2 , Laura Campbell-Sills 1 , Chia-Yen Chen 4, 5, 6 , Joel Gelernter 7, 8, 9 , Feng He 2 , Steven G Heeringa 10 , Adam X Maihofer 1 , Caroline Nievergelt 1 , Matthew K Nock 11 , Stephan Ripke 5, 12, 13 , Xiaoying Sun 2 , Ronald C Kessler 14 , Jordan W Smoller 4, 5, 6 , Robert J Ursano 15
Affiliation  

Though a growing body of preclinical and translational research is illuminating a biological basis for resilience to stress, little is known about the genetic basis of psychological resilience in humans. We conducted genome-wide association studies (GWASs) of self-assessed (by questionnaire) and outcome-based (incident mental disorders from predeployment to postdeployment) resilience among European (EUR) ancestry soldiers in the Army study to assess risk and resilience in servicemembers. Self-assessed resilience (N = 11,492) was found to have significant common-variant heritability (h2 = 0.162, se = 0.050, p = 5.37 × 10-4 ), and to be significantly negatively genetically correlated with neuroticism (rg  = -0.388, p = .0092). GWAS results from the EUR soldiers revealed a genome-wide significant locus on an intergenic region on Chr 4 upstream from doublecortin-like kinase 2 (DCLK2) (four single nucleotide polymorphisms (SNPs) in LD; top SNP: rs4260523 [p = 5.65 × 10-9 ] is an eQTL in frontal cortex), a member of the doublecortin family of kinases that promote survival and regeneration of injured neurons. A second gene, kelch-like family member 36 (KLHL36) was detected at gene-wise genome-wide significance [p = 1.89 × 10-6 ]. A polygenic risk score derived from the self-assessed resilience GWAS was not significantly associated with outcome-based resilience. In very preliminary results, genome-wide significant association with outcome-based resilience was found for one locus (top SNP: rs12580015 [p = 2.37 × 10-8 ]) on Chr 12 downstream from solute carrier family 15 member 5 (SLC15A5) in subjects (N = 581) exposed to the highest level of deployment stress. The further study of genetic determinants of resilience has the potential to illuminate the molecular bases of stress-related psychopathology and point to new avenues for therapeutic intervention.

中文翻译:

美国陆军士兵心理弹性的全基因组分析。

尽管越来越多的临床前和转化研究阐明了压力恢复力的生物学基础,但人们对人类心理恢复力的遗传基础知之甚少。我们对陆军研究中的欧洲 (EUR) 血统士兵进行了自我评估(通过问卷调查)和基于结果(从部署前到部署后的精神障碍事件)恢复力的全基因组关联研究 (GWAS),以评估现役军人的风险和恢复力. 自我评估的复原力 (N = 11,492) 被发现具有显着的共同变异遗传力 (h2 = 0.162, se = 0.050, p = 5.37 × 10-4),并且与神经质呈显着的负遗传相关性 (rg = -0.388 , p = .0092)。来自 EUR 士兵的 GWAS 结果揭示了双皮质素样激酶 2 (DCLK2) 上游 Chr 4 基因间区域的全基因组显着位点(LD 中的四个单核苷酸多态性 (SNP);顶部 SNP:rs4260523 [p = 5.65 × 10-9 ] 是额叶皮层中的一个 eQTL),是促进受损神经元存活和再生的双皮质激酶家族成员。第二个基因,kelch 样家族成员 36 (KLHL36) 在全基因组显着性上被检测到 [p = 1.89 × 10-6]。来自自我评估的弹性 GWAS 的多基因风险评分与基于结果的弹性没有显着相关性。在非常初步的结果中,发现一个位点(顶部 SNP:rs12580015 [p = 2. 37 × 10-8 ]) 在溶质载体家族 15 成员 5 (SLC15A5) 下游的 Chr 12 上,受试者 (N = 581) 暴露于最高水平的部署压力。对恢复力的遗传决定因素的进一步研究有可能阐明与压力相关的精神病理学的分子基础,并指出治疗干预的新途径。
更新日期:2019-11-01
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