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两个高危人群创伤后应激障碍的全基因组关联研究

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

作者信息

Melroy-Greif Whitney E, Wilhelmsen Kirk C, Yehuda Rachel, Ehlers Cindy L

机构信息

Department of Neuroscience,The Scripps Research Institute,La Jolla,CA,USA.

Department of Genetics and Neurology,University of North Carolina,Chapel Hill,NC,USA.

出版信息

Twin Res Hum Genet. 2017 Jun;20(3):197-207. doi: 10.1017/thg.2017.12. Epub 2017 Mar 6.


DOI:10.1017/thg.2017.12
PMID:28262088
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5479352/
Abstract

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.

摘要

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。

相似文献

[1]
Genome-Wide Association Study of Post-Traumatic Stress Disorder in Two High-Risk Populations.

Twin Res Hum Genet. 2017-6

[2]
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[3]
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[5]
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[6]
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[7]
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[8]
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[9]
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[10]
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[3]
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[4]
Using Monozygotic Twins to Dissect Common Genes in Posttraumatic Stress Disorder and Migraine.

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[5]
A review of epigenetic contributions 
to post-traumatic stress disorder
.

Dialogues Clin Neurosci. 2019-12

[6]
CR-19-0950: Event-related responses to alcohol-related stimuli in Mexican-American young adults: Relation to age, gender, comorbidity and "dark side" symptoms.

Drug Alcohol Depend. 2019-7-6

[7]
A Review of Epigenetics of PTSD in Comorbid Psychiatric Conditions.

Genes (Basel). 2019-2-13

[8]
Prevalence of acute stress disorder among road traffic accident survivors: a meta-analysis.

BMC Psychiatry. 2018-6-13

[9]
Recent Genetics and Epigenetics Approaches to PTSD.

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[10]
Spatial Epidemiology of Alcohol- and Drug-Related Health Problems Among Northern Plains American Indians: Nebraska and South Dakota, 2007 to 2012.

Alcohol Clin Exp Res. 2018-1-30

本文引用的文献

[1]
Lifetime history of traumatic events in a young adult Mexican American sample: Relation to substance dependence, affective disorder, acculturation stress, and PTSD.

J Psychiatr Res. 2016-12

[2]
Genome-wide Association Studies of Posttraumatic Stress Disorder in 2 Cohorts of US Army Soldiers.

JAMA Psychiatry. 2016-7-1

[3]
Genome-wide association study of posttraumatic stress disorder in a cohort of Iraq-Afghanistan era veterans.

J Affect Disord. 2015-9-15

[4]
Differential odor sensitivity in PTSD: Implications for treatment and future research.

J Affect Disord. 2015-7-1

[5]
Second-generation PLINK: rising to the challenge of larger and richer datasets.

Gigascience. 2015-2-25

[6]
Protective variant associated with alcohol dependence in a Mexican American cohort.

BMC Med Genet. 2014-12-21

[7]
Genomic predictors of combat stress vulnerability and resilience in U.S. Marines: A genome-wide association study across multiple ancestries implicates PRTFDC1 as a potential PTSD gene.

Psychoneuroendocrinology. 2015-1

[8]
From FastQ data to high confidence variant calls: the Genome Analysis Toolkit best practices pipeline.

Curr Protoc Bioinformatics. 2013

[9]
Statistical power and significance testing in large-scale genetic studies.

Nat Rev Genet. 2014-5

[10]
Variant calling in low-coverage whole genome sequencing of a Native American population sample.

BMC Genomics. 2014-1-30

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