Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records.

Genome-wide Association Study of Dimensional Psychopathology Using Electronic Health Records.
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DOI:
10.1016/j.biopsych.2017.12.004
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发表时间:
2018-06-15
影响因子:
10.6
通讯作者:
Perlis RH
Perlis RH
中科院分区:
医学1区
文献类型:
--
作者:
McCoy TH Jr;Castro VM;Hart KL;Pellegrini AM;Yu S;Cai T;Perlis RH

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神经精神疾病的遗传学研究强烈提示责任重叠。有越来越多的努力来表征这些疾病的维度,而不是分类,但在何种程度上,这种维度模型对应于生物学是未知的。我们应用了一种新开发的自然语言处理(NLP)方法,根据NIMH研究领域标准(RDoC)的定义,从一个大型生物银行的叙述性出院记录中提取五个症状维度。我们进行了一项全基因组关联研究,以检查常见变异是否与这些维度中的每一个作为数量性状相关。在4,687名个体中,五个领域中有三个领域的基因座超过了全基因组统计学显著性阈值。其中包括一个跨越新皮层发育基因RFPL 3和RFPL 3S的基因座,用于唤醒(p=2.29e-8),一个跨越FPR 3基因的基因座,用于认知(p=3.22e-8)。NLP识别维度表型,可能有助于发现与精神病理学相关的常见遗传变异。
Genetic studies of neuropsychiatric disease strongly suggest overlap in liability. There are growing efforts to characterize these diseases dimensionally rather than categorically, but the extent to which such dimensional models correspond to biology is unknown. We applied a newly-developed natural language processing (NLP) method to extract five symptom dimensions, based on the NIMH Research Domain Criteria (RDoC) definitions, from narrative hospital discharge notes in a large biobank. We conducted a genome-wide association study to examine whether common variants were associated with each of these dimensions as quantitative traits. Among 4,687 individuals, loci in three of five domains exceeded a genome-wide threshold for statistical significance. These included a locus spanning the neocortical development genes RFPL3 and RFPL3S, for arousal (p=2.29e–8), and one spanning the FPR3 gene, for cognition (p=3.22e–8). NLP identifies dimensional phenotypes that may facilitate discovery of common genetic variation relevant to psychopathology.
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