双相情感障碍
AKT1型
葛兰素史克-3
遗传学
遗传关联
全基因组关联研究
精神病
单核苷酸多态性
生物
心理学
生物信息学
心情
精神科
基因
激酶
基因型
蛋白激酶B
磷酸化
作者
Vincent Millischer,Granville J. Matheson,Lina Martinsson,Inger Römer Ek,Martin Schalling,Catharina Lavebratt,Lena Backlund
标识
DOI:10.1016/j.psychres.2019.112677
摘要
AKT1 encodes a serine/threonine kinase that has as one of its best-known substrates glycogen synthase kinase-3 (GSK3), a primary target for lithium. AKT1 has been previously been implicated as a vulnerability gene for bipolar disorder (BD). We aimed to associate genetic variants in the AKT1 gene with subgroups of BD. BD patients from a Swedish cohort (N = 831) were phenotyped in regards to their psychotic episodes according to mood-congruence in depression and manias, and compared to controls (N = 1,496). All participants were genotyped for SNPs in AKT1 previously implicated to have a role: rs3730358, rs1130214 and rs3803300. None of the effects reported in earlier studies were statistically significant, including the association between rs3803300 and BD without any psychotic symptoms, rs3803300 and mood-congruent psychosis, rs3803300 and the combined groups, as well as the association between the haplotypes formed by rs3730358 and rs1130214 and risk for BD. In a Bayesian analysis, all Bayes' Factors using default priors supported the null hypothesis in the replication set by a factor of between 5 and 1300 times. Analysis of genome wide association data did not reveal any association between BD and the AKT1 region. We conclude AKT1 is less likely to be a vulnerability gene in BD.
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