Genome-wide significant regions in 43 Utah high-risk families implicate multiple genes involved in risk for completed suicide.
Genome-wide significant regions in 43 Utah high-risk families implicate multiple genes involved in risk for completed suicide.
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犹他州43个高风险家族的全基因组重要区域暗示了涉及完整自杀风险的多个基因。
DOI：
10.1038/s41380-018-0282-3
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发表时间：
2020-11
影响因子：
11
通讯作者：
Gray D
中科院分区：
文献类型：
--
作者：
Coon H;Darlington TM;DiBlasi E;Callor WB;Ferris E;Fraser A;Yu Z;William N;Das SC;Crowell SE;Chen D;Anderson JS;Klein M;Jerominski L;Cannon D;Shabalin A;Docherty A;Williams M;Smith KR;Keeshin B;Bakian AV;Christensen E;Li QS;Camp NJ;Gray D
自杀是美国第十大死因。尽管环境有不可否认的影响，但有证据表明，遗传因素在完全自杀中起着重要作用。我们将从犹他州法医处获得的完整自杀病例的~ 4500个DNA样本资源与800多万人的家谱记录和医疗记录数据联系起来。这种联系导致了高危大家庭(7-9代)的确定，这些家庭有完全自杀的重大家庭风险。远亲的家族聚集会将共享环境的影响降至最低，提供更多遗传同质性的风险群体，并通过家族重复放大遗传风险。我们分析了43个高危家系的自杀案例中的发光杆菌心理阵列基因，确定了30个不同的共享基因组片段，这些片段具有全基因组证据(p = 2.02E-07-1.30E-18)，表明完全自杀是分离的。共有区域涉及的207个基因为进一步研究提供了一组有重点的基因；18个基因以前与自杀风险有关。虽然心理阵列变异并不代表207个基因中的所有变异，但我们研究了这些变异在高危家族中的特定分离，以及在~ 1300例与发现家族无关的犹他州自杀中变异与预测功能影响的关联。没有一种有限的心理阵列变异解释了高危家庭的分离；需要对这些区域进行测序才能发现分离的风险变异，这可能是更罕见的或受监管的。然而，额外的关联测试产生了四个显著的心理阵列变异(SP110，rs181058279；AGBL2，rs76215382；SUCLA2，rs121908538；APH1B，rs745918508)，增加了这些基因赋予完全自杀风险的可能性。
Suicide is the 10th leading cause of death in the United States. Although environment has undeniable impact, evidence suggests that genetic factors play a significant role in completed suicide. We linked a resource of ~ 4500 DNA samples from completed suicides obtained from the Utah Medical Examiner to genealogical records and medical records data available on over eight million individuals. This linking has resulted in the identification of high-risk extended families (7–9 generations) with significant familial risk of completed suicide. Familial aggregation across distant relatives minimizes effects of shared environment, provides more genetically homogeneous risk groups, and magnifies genetic risks through familial repetition. We analyzed Illumina PsychArray genotypes from suicide cases in 43 high-risk families, identifying 30 distinct shared genomic segments with genome-wide evidence (p = 2.02E-07–1.30E-18) of segregation with completed suicide. The 207 genes implicated by the shared regions provide a focused set of genes for further study; 18 have been previously associated with suicide risk. Although PsychArray variants do not represent exhaustive variation within the 207 genes, we investigated these for specific segregation within the high-risk families, and for association of variants with predicted functional impact in ~ 1300 additional Utah suicides unrelated to the discovery families. None of the limited PsychArray variants explained the high-risk family segregation; sequencing of these regions will be needed to discover segregating risk variants, which may be rarer or regulatory. However, additional association tests yielded four significant PsychArray variants (SP110, rs181058279; AGBL2, rs76215382; SUCLA2, rs121908538; APH1B, rs745918508), raising the likelihood that these genes confer risk of completed suicide.
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影响因子：
64.5
作者：
GRODEN, J;THLIVERIS, A;WHITE, R
通讯作者：
WHITE, R
影响因子：
64.5
作者：
Boyle EA;Li YI;Pritchard JK
通讯作者：
Pritchard JK
影响因子：
9.2
作者：
Chang CC;Chow CC;Tellier LC;Vattikuti S;Purcell SM;Lee JJ
通讯作者：
Lee JJ
影响因子：
8.6
作者：
Bekris, Lynn M.;Tsuang, Debby W.;Peskind, Elaine R.;Yu, Chang E.;Montine, Thomas J.;Zhang, Jing;Zabetian, Cyrus P.;Leverenz, James B.
通讯作者：
Leverenz, James B.
影响因子：
6.8
作者：
Flory, J. D.;Donohue, D.;Yehuda, R.
通讯作者：
Yehuda, R.