Cognitive impairment is a frequent and serious problem in patients with various forms of severe mental illnesses (SMI), including schizophrenia (SZ) and bipolar disorder (BP). Recent research suggests genetic links to several cognitive phenotypes in both SMI and in the general population. Our goal in this study was to identify potential genomic signatures of cognitive functioning in veterans with severe mental illness and compare them to previous findings for cognition across different populations. Veterans Affairs (VA) Cooperative Studies Program (CSP) Study #572 evaluated cognitive and functional capacity measures among SZ and BP patients. In conjunction with the VA Million Veteran Program, 3,959 European American (1,095 SZ, 2,864 BP) and 2,601 African American (1,095 SZ, 2,864 BP) patients were genotyped using a custom Affymetrix Axiom Biobank array. We performed a genome‐wide association study of global cognitive functioning, constructed polygenic scores for SZ and cognition in the general population, and examined genetic correlations with 2,626 UK Biobank traits. Although no single locus attained genome‐wide significance, observed allelic effects were strongly consistent with previous studies. We observed robust associations between global cognitive functioning and polygenic scores for cognitive performance, intelligence, and SZ risk. We also identified significant genetic correlations with several cognition‐related traits in UK Biobank. In a diverse cohort of U.S. veterans with SZ or BP, we demonstrate broad overlap of common genetic effects on cognition in the general population, and find that greater polygenic loading for SZ risk is associated with poorer cognitive performance.

中文翻译：

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全基因组关联研究对美国精神分裂症或双相情感障碍退伍军人的认知能力。

在患有各种形式的严重精神疾病（SMI），包括精神分裂症（SZ）和躁郁症（BP）的患者中，认知障碍是一个常见且严重的问题。最近的研究表明，与SMI和普通人群中的几种认知表型有遗传联系。我们在这项研究中的目标是确定患有严重精神疾病的退伍军人的认知功能的潜在基因组特征，并将其与先前的发现进行比较，以在不同人群中进行认知。退伍军人事务（VA）合作研究计划（CSP）研究＃572对SZ和BP患者的认知能力和功能能力进行了评估。结合VA百万退伍军人计划，3,959美国人（1,095 SZ，2,864 BP）和2,601非洲裔美国人（1,095 SZ，2，使用定制的Affymetrix Axiom Biobank阵列对864 BP）患者进行基因分型。我们进行了全球认知功能的全基因组关联研究，构建了普通人群中SZ和认知的多基因评分，并检查了与2,626个英国生物库特征的遗传相关性。尽管没有单个基因座在全基因组范围内具有重要意义，但观察到的等位基因效应与以前的研究强烈一致。我们观察到全球认知功能与认知表现，智力和SZ风险的多基因评分之间的牢固关联。我们还发现了英国生物库中与几个认知相关性状的显着遗传相关性。在具有SZ或BP的美国退伍军人的不同队列中，我们证明了普通基因对普通人群认知的广泛重叠，