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TSNAX/DISC1 基因座与精神分裂症和双相情感障碍在南印度人群中的性别特异性关联。

Gender-specific association of TSNAX/DISC1 locus for schizophrenia and bipolar affective disorder in South Indian population.

机构信息

Department of Psychiatry, Molecular Genetics Laboratory, National Institute of Mental Health and Neuro Sciences, Bangalore, India.

出版信息

J Hum Genet. 2012 Aug;57(8):523-30. doi: 10.1038/jhg.2012.62. Epub 2012 Jun 7.

Abstract

Genetic association studies have implicated the TSNAX/DISC1 (disrupted in schizophrenia 1) in schizophrenia (SCZ), bipolar affective disorder (BPAD) and major depression. This study was performed to assess the possible involvement of TSNAX/DISC1 locus in the aetiology of BPAD and SCZ in the Southern Indian population. We genotyped seven single nucleotide polymorphism (SNPs) from TSNAX/DISC1 region in 1252 individuals (419 BPAD patients, 408 SCZ patients and 425 controls). Binary logistic regression revealed a nominal association for rs821616 in DISC1 for BPAD and also combined cases of BPAD or SCZ, but after correcting for multiple testing, these results were non-significant. However, significant association was observed with BPAD, as well as combined cases of BPAD or SCZ, within the female subjects for the rs766288 after applying false discovery rate corrections at the 0.05 level. Two-locus analysis showed C-C (rs766288-rs2812393) as a risk combination in BPAD, and G-T (rs2812393-rs821616) as a protective combination in SCZ and combined cases of BPAD or SCZ. Female-specific associations were observed for rs766288-rs2812393, rs766288-rs821616 and rs8212393-rs821616 in two-locus analysis. Our results provide further evidence for sex-dependent effects of the TSNAX/DISC1 locus in the aetiology of SCZ and BPAD.

摘要

遗传关联研究表明,TSNAX/DISC1(精神分裂症 1 中缺失)与精神分裂症(SCZ)、双相情感障碍(BPAD)和重度抑郁症有关。本研究旨在评估 TSNAX/DISC1 基因座在南部印度人群中 BPAD 和 SCZ 发病机制中的可能作用。我们对来自 TSNAX/DISC1 区域的 7 个单核苷酸多态性(SNP)在 1252 名个体(419 名 BPAD 患者、408 名 SCZ 患者和 425 名对照者)中进行了基因分型。二元逻辑回归显示,DISC1 中的 rs821616 与 BPAD 存在名义关联,也与 BPAD 或 SCZ 的合并病例有关,但在进行多重检验校正后,这些结果没有统计学意义。然而,在应用假发现率校正后,rs766288 在女性中与 BPAD 以及 BPAD 或 SCZ 的合并病例均有显著关联。双位点分析显示,rs766288-rs2812393 为 BPAD 的风险组合,rs2812393-rs821616 为 SCZ 和 BPAD 或 SCZ 合并病例的保护组合。在双位点分析中,rs766288-rs2812393、rs766288-rs821616 和 rs8212393-rs821616 均观察到女性特异性关联。我们的结果进一步提供了 TSNAX/DISC1 基因座在 SCZ 和 BPAD 发病机制中存在性别依赖性影响的证据。

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