Overlapping genetic effects between suicidal ideation and neurocognitive functioning
Overlapping genetic effects between suicidal ideation and neurocognitive functioning
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DOI：
10.1016/j.jad.2019.02.003
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发表时间：
2019-04-15
影响因子：
6.6
通讯作者：
Palmer, Rohan H. C.
中科院分区：
文献类型：
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作者：
Brick, Leslie A.;Marraccini, Marisa E.;Palmer, Rohan H. C.
背景：自杀是青少年和青年死亡的第二大原因。几项研究表明，基因对自杀相关表型有显著影响，神经生物学研究越来越多的证据表明，神经认知能力的缺陷与自杀表型有关。本研究的目的是在大量青少年样本中估计自杀意念（SI）的遗传性，并确定SI是否与神经认知功能相关。方法：从费城神经发育队列中提取全基因组数据（N = 3564名无血缘关系的欧洲血统个体）。青少年完成了一项精神病学评估，以及一项计算机化的神经认知测试，以评估四个领域的表现：记忆、执行功能、社会认知和复杂认知。使用基因组关联矩阵限制最大似然（GREML）估计来确定SI的SNP遗传力(h（SNP)(2)）以及SI与神经认知域之间的遗传相关性（r(G)）。结果：近17%的青少年报告了性侵犯。SI的SNP-遗传力估计具有边际显著性(h（SNP)(2) = 11%, SE = 8%, p = 0.086）。双变量分析表明，SI与情绪识别之间存在显著的r(G) (r(G) = 0.79, SE = 0.45, p = 0.006；表型相关r = 0.04, p = 0.017)。局限性：SI可能代表了一种与自杀企图/自杀未遂和其他共病精神病理相关但不同的遗传结构。此外，尽管遗传相关性指出了性状之间共有的遗传因素，但无法推断出直接的因果机制。结论：常见的遗传因素有助于SI和神经认知功能的变化。影响情绪认同的遗传因素与SI存在显著的遗传重叠。
Background: Suicide is the second leading cause of death among adolescents and young adults. Several studies have indicated significant genetic influences on suicide-related phenotypes and mounting evidence from neurobiological research has linked deficits in neurocognitive abilities to suicide phenotypes. The goal of the present study was to estimate the heritability of suicidal ideation (SI) in a large sample of adolescents and determine if SI is genetically correlated with neurocognitive functioning.Methods: Genome-wide data (N = 3564 unrelated individuals of European Ancestry) were drawn from the Philadelphia Neurodevelopment Cohort. Adolescents completed a psychiatric assessment, as well as a computerized neurocognitive battery to assess performance across four domains: memory, executive function, social cognition, and complex cognition. Genomic-relatedness-matrix restricted maximum likelihood (GREML) estimation was used to determine SNP-heritability (h(SNP)(2)) of SI and the genetic correlation (r(G)) between SI and neurocognitive domains.Results: Nearly 17% of adolescents reported SI. The SNP-heritability estimate for SI was marginally significant (h(SNP)(2) = 11%, SE = 8%, p = 0.086). Bivariate analyses indicated a significant r(G) between SI and emotion identification (r(G) = 0.79, SE = 0.45, p = 0.006; phenotypic correlation r = 0.04, p = 0.017).Limitations: It is possible that SI may represent a related, but differentially heritable construct from suicide attempts/completion and other comorbid psychopathology. Additionally, though genetic correlations point to shared genetic factors across traits, direct causal mechanisms cannot be deduced.Conclusions: Common heritable factors contribute to variation in SI and neurocognitive functioning. Genetic factors influencing emotion identification have significant genetic overlap with SI.