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Associations of Homer Scaffolding Protein 1 gene and psychological correlates with suicide attempts in Chinese: A pilot study of multifactorial risk model.

Gene. 2018 Dec 30;679:382-388. Epub 2018 Sep 13
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摘要


BACKGROUND:Suicide is a fatal outcome for subjects with mental ill-health. Genetic factors and psychological correlates are believed to contribute to the risk of suicide attempts (SA), whereas both factors are reported to exert a small effect. This study therefore tried to investigate if combination of the two aspects can enhance the explanation of variance in SA. METHODS:A common variant rs7713917 in HOMER1 gene was genotyped for 333 Chinese psychiatric patients with or without SA. Multifactorial risk models comprised of this variant and psychological correlates were identified by logistic regression analysis (LRA) and Multifactor Dimensionality Reduction (MDR) method separately, and then evaluated for their performance by biostatistical methods. RESULTS:An association of A-carrier genotypes in rs7713917 with an increased risk of SA was observed (OR = 1.79, 95% CI = 1.08-2.98). Although with a medium effect size, this variant alone could only explain 1.9% variance of SA. Interestingly, this study was the first time to show that the association of the rs7713917 and SA was significantly mediated by the NEO conscientiousness (NEOC) dimension (p-value = 0.002), with a greater genetic effect observed in subjects with a low NEO-C level (OR = 2.89, 95% CI = 1.16-7.18) but not in subjects with an average or high level. Upon the LRA method, the multifactorial risk model constituted of the two interacted factors and their interaction effect could explain up to 17.0% variance, which was almost 9-fold higher than the one explained by the rs7713917 alone. Furthermore, this model owned a higher effectiveness than the three models identified by the MDR method (p-value < 0.0007). CONCLUSIONS:The present study identified an effective multifactorial risk model, in which the combination of the HOMER1 variant and the NEO-C dimension could enhance explanation of the variance of SA in Chinese. This pilot study may provide a novel avenue to investigate the pathogenesis of SA in psychiatric patients.

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