Age-related cognitive decline (ACD) is the gradual process of decreasing of cognitive function over age. Most genetic risk factors for ACD have been identified in European populations and there are no reports in admixed Latin American individuals. We performed admixture mapping, genome-wide association analysis (GWAS), and fine-mapping to examine genetic factors associated with 15-year cognitive trajectory in 1,407 Brazilian older adults, comprising 14,956 Mini-Mental State Examination measures. Participants were enrolled as part of the Bambuí-Epigen Cohort Study of Aging. Our admixture mapping analysis identified a genomic region (3p24.2) in which increased Native American ancestry was significantly associated with faster ACD. Fine-mapping of this region identified a single nucleotide polymorphism (SNP) rs142380904 (β = -0.044, SE = 0.01, p = 7.5 × 10-5) associated with ACD. In addition, our GWAS identified 24 associated SNPs, most in genes previously reported to influence cognitive function. The top six associated SNPs accounted for 18.5% of the ACD variance in our data. Furthermore, our longitudinal study replicated previous GWAS hits for cognitive decline and Alzheimer's disease. Our 15-year longitudinal study identified both ancestry-specific and cosmopolitan genetic variants associated with ACD in Brazilians, highlighting the need for more trans-ancestry genomic studies, especially in underrepresented ethnic groups.

译文

:年龄相关的认知能力下降(ACD)是随着年龄增长而认知功能逐渐下降的过程。在欧洲人群中已经发现了大多数ACD的遗传风险因素,在混合的拉丁美洲人中没有任何报道。我们进行了混合作图,全基因组关联分析(GWAS)和精细映射,以检查与1,407名巴西老年人的15年认知轨迹有关的遗传因素,包括14,956项迷你精神状态检查措施。参加者参加了Bambuí-Epigen老年研究队列。我们的掺混物作图分析确定了一个基因组区域(3p24.2),其中美洲原住民血统增加与更快的ACD密切相关。对该区域的精细映射鉴定了与ACD相关的单核苷酸多态性(SNP)rs142380904(β==-0.044,SE == 0.01,p == 7.5 =×10-5)。此外,我们的GWAS还鉴定了24个相关的SNP,其中大多数在先前报道过影响认知功能的基因中。在我们的数据中,排名前六位的相关SNP占ACD方差的18.5%。此外,我们的纵向研究复制了先前的GWAS减低认知功能和阿尔茨海默氏病的命中率。我们进行了15年的纵向研究,确定了巴西人与ACD相关的祖先特异性和世界性遗传变异,强调需要进行更多的跨祖先的基因组研究,尤其是在代表性不足的族裔群体中。

+1
+2
100研值 100研值 ¥99课程
检索文献一次
下载文献一次

去下载>

成功解锁2个技能,为你点赞

《SCI写作十大必备语法》
解决你的SCI语法难题!

技能熟练度+1

视频课《玩转文献检索》
让你成为检索达人!

恭喜完成新手挑战

手机微信扫一扫,添加好友领取

免费领《Endnote文献管理工具+教程》

微信扫码, 免费领取

手机登录

获取验证码
登录