The functional architecture of the brain is composed of distinct networks, where higher system segregation, i.e. greater differentiation of such functional networks, is associated with better cognitive performance. Aging and many neurological diseases have been associated with reduced system segregation and thus cognitive impairment. The genetic basis and risk factors of system segregation are largely unknown. Here, we present the first genome-wide association study of fMRI-assessed system segregation in 16,635 UK Biobank participants, identifying nine independent genomic loci. The 66 implicated genes were significantly downregulated in brain tissue and upregulated in vascular tissue. Of major vascular risk factors (Life’s Simple 7), blood pressure showed a robust genetic correlation with system segregation. Observational and Mendelian randomization analyses confirmed a unfavourable effect of higher blood pressure on system segregation and of lower system segregation on cognition. Replication analyses in 2,414 Rotterdam Study participants supported these conclusions.

中文翻译：

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遗传变异将大脑网络的较低隔离与一般老龄化人群中的高血压和认知能力下降联系起来

大脑的功能结构由不同的网络组成，其中更高的系统隔离，即这种功能网络的更大差异，与更好的认知表现相关。衰老和许多神经系统疾病与系统隔离减少和认知障碍有关。系统分离的遗传基础和风险因素在很大程度上是未知的。在这里，我们在 16,635 名英国生物银行参与者中展示了第一个 fMRI 评估系统分离的全基因组关联研究，确定了 9 个独立的基因组位点。66 个相关基因在脑组织中显着下调，在血管组织中上调。在主要血管危险因素（Life's Simple 7）中，血压显示出与系统分离的强烈遗传相关性。观察性和孟德尔随机化分析证实了较高的血压对系统隔离和较低的系统隔离对认知的不利影响。2,414 名鹿特丹研究参与者的重复分析支持这些结论。