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Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
Psychological Medicine ( IF 5.9 ) Pub Date : 2021-07-07 , DOI: 10.1017/s003329172100266x
Emma C Johnson 1 , Manav Kapoor 2 , Alexander S Hatoum 1 , Hang Zhou 3, 4 , Renato Polimanti 3, 4 , Frank R Wendt 3, 4 , Raymond K Walters 5, 6 , Dongbing Lai 7 , Rachel L Kember 8, 9 , Sarah Hartz 1 , Jacquelyn L Meyers 10, 11 , Roseann E Peterson 12 , Stephan Ripke 5, 6, 13 , Tim B Bigdeli 10 , Ayman H Fanous 10 , Carlos N Pato 10 , Michele T Pato 10 , Alison M Goate 2 , Henry R Kranzler 8, 9 , Michael C O'Donovan 14 , James T R Walters 14 , Joel Gelernter 3, 4, 15, 16 , Howard J Edenberg 7, 17 , Arpana Agrawal 1
Affiliation  

Background

Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders.

Methods

We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific.

Results

We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001).

Conclusions

Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.



中文翻译:


精神分裂症和酒精使用障碍背后的趋同和趋异遗传影响的调查


 背景


酒精使用障碍 (AUD) 和精神分裂症 (SCZ) 经常同时发生,大规模全基因组关联研究 (GWAS) 已经发现这些疾病之间存在显着的遗传相关性。

 方法


我们使用最大的已发表的 AUD(总病例 = 77 822)和 SCZ(总病例 = 46 827)的 GWAS 来识别影响这两种疾病(具有相同或相反作用方向)和特定疾病的遗传变异。

 结果


我们鉴定了 55 个独立的全基因组显着单核苷酸多态性,对 AUD 和 SCZ 具有相同的作用方向,8 个具有相反方向的强大作用,98 个具有疾病特异性作用。我们还发现了 12 个基因的证据,这些基因与 AUD 和 SCZ 的多效性关联与前额皮质中基因表达的调节一致。 AUD 和 SCZ 之间的遗传协方差集中在脑组织中具有功能的基因组区域( p = 0.001)。

 结论


我们的研究结果进一步证明 SCZ 与 AUD 具有有意义的基因重叠。

更新日期:2021-07-07
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