Performance of polygenic scores for predicting phobic anxiety.
Performance of polygenic scores for predicting phobic anxiety.
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DOI：
10.1371/journal.pone.0080326
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发表时间：
2013
期刊：
影响因子：
3.7
通讯作者：
Kubzansky LD
中科院分区：
文献类型：
--
作者：
Walter S;Glymour MM;Koenen K;Liang L;Tchetgen Tchetgen EJ;Cornelis M;Chang SC;Rimm E;Kawachi I;Kubzansky LD
焦虑症很常见，在美国的终生患病率为20%，是导致残疾、误工和医疗保健利用的沉重负担的原因。到目前为止，还没有发现焦虑症、焦虑症或相关特征的因果遗传变异。为了调查恐惧症症状评分是否与3个备选多基因风险评分相关，这些多基因风险评分来自外部全基因组范围的焦虑症关联研究、内部估计的不可知性多基因评分或先前确定的候选基因。纵向随访研究。使用线性和逻辑回归方法，我们调查了恐惧症是否与多基因风险分数有关，这些多基因风险分数来自31个候选基因的内部、遗漏全基因组关联研究，以及先前被证明在另一个队列中预测抑郁和焦虑的样本外全基因组关联权重。研究参与者(n = 11,127)是护士健康研究和卫生专业人员随访研究的个人。在两个时间点通过皇冠脆皮指数的8项恐怖焦虑量表评估焦虑症状，并由此得出连续的表型评分。我们没有发现全基因组范围内的显著关联与恐惧症焦虑。恐惧症也与多基因风险分数无关，该多基因风险分数来自使用自由p值阈值的全基因组关联研究贝塔权重；与先前发表的全基因组多基因分数；或与基于先前假设预测焦虑的31个基因的候选基因风险分数无关。双胞胎研究对焦虑症的遗传率估计在20%-40%之间，与全基因组关联结果解释的遗传率之间有很大差距。新的方法，如改进的基因组拼接，应用基因表达和生物途径信息，以及纳入遗传风险的社会或环境修饰物，可能是识别焦虑的重要遗传预测因素所必需的。
Anxiety disorders are common, with a lifetime prevalence of 20% in the U.S., and are responsible for substantial burdens of disability, missed work days and health care utilization. To date, no causal genetic variants have been identified for anxiety, anxiety disorders, or related traits. To investigate whether a phobic anxiety symptom score was associated with 3 alternative polygenic risk scores, derived from external genome-wide association studies of anxiety, an internally estimated agnostic polygenic score, or previously identified candidate genes. Longitudinal follow-up study. Using linear and logistic regression we investigated whether phobic anxiety was associated with polygenic risk scores derived from internal, leave-one out genome-wide association studies, from 31 candidate genes, and from out-of-sample genome-wide association weights previously shown to predict depression and anxiety in another cohort. Study participants (n = 11,127) were individuals from the Nurses' Health Study and Health Professionals Follow-up Study. Anxiety symptoms were assessed via the 8-item phobic anxiety scale of the Crown Crisp Index at two time points, from which a continuous phenotype score was derived. We found no genome-wide significant associations with phobic anxiety. Phobic anxiety was also not associated with a polygenic risk score derived from the genome-wide association study beta weights using liberal p-value thresholds; with a previously published genome-wide polygenic score; or with a candidate gene risk score based on 31 genes previously hypothesized to predict anxiety. There is a substantial gap between twin-study heritability estimates of anxiety disorders ranging between 20–40% and heritability explained by genome-wide association results. New approaches such as improved genome imputations, application of gene expression and biological pathways information, and incorporating social or environmental modifiers of genetic risks may be necessary to identify significant genetic predictors of anxiety.
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影响因子：
10.6
作者：
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通讯作者：
Turecki, Gustavo
影响因子：
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通讯作者：
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