Cho Seung Bin, Aliev Fazil, Clark Shaunna L, Adkins Amy E, Edenberg Howard J, Bucholz Kathleen K, Porjesz Bernice, Dick Danielle M
Department of Psychology, Virginia Commonwealth University, PO Box 842018, 817W. Franklin Street, Richmond, VA, 23284-2018, USA.
College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA.
Behav Genet. 2017 Jul;47(4):405-415. doi: 10.1007/s10519-017-9844-4. Epub 2017 Mar 25.
Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European-American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399). In the 3-class model, classes were characterized by overall low associations (85.6% of SNPs), relatively stronger association only with MD (6.8%), and stronger associations with AD and ASP but not with MD (7.6%), respectively. These results parallel the genetic factor structure identified in twin studies. The findings suggest that applying LPA to association results across multiple disorders may be a promising approach to identify the specific genetic etiologies underlying shared genetic variance.
双胞胎研究表明，潜在遗传因素在共病精神障碍中存在重叠。在本研究中，我们采用了一种新方法，通过根据单核苷酸多态性的全基因组关联模式进行聚类，来阐明跨精神疾病结局的共享遗传因素。我们将潜在剖面分析（LPA）应用于全基因组关联研究的p值，该研究涉及三种表型：酒精依赖（AD）、反社会人格障碍（ASP）和重度抑郁（MD）的症状计数，使用了酒精中毒遗传学合作研究中的欧美病例对照全基因组关联研究子样本（N = 1399）。在三类模型中，各类别的特征分别为总体关联较低（85.6%的单核苷酸多态性）、仅与MD的关联相对较强（6.8%）以及与AD和ASP的关联较强但与MD的关联不强（7.6%）。这些结果与双胞胎研究中确定的遗传因素结构相似。研究结果表明，将LPA应用于多种疾病的关联结果可能是一种有前景的方法，用于识别共享遗传变异背后的特定遗传病因。
