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全基因组关联研究在多民族队列中的执行功能表明 LINC01362:来自北方曼哈顿研究的结果。

Genome-wide association study of executive function in a multi-ethnic cohort implicates LINC01362: Results from the northern Manhattan study.

机构信息

John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.

John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA; Dr. John T. Macdonald, Department of Human Genetics, University of Miami, Miami, FL USA.

出版信息

Neurobiol Aging. 2023 Mar;123:216-221. doi: 10.1016/j.neurobiolaging.2022.11.016. Epub 2022 Dec 5.

Abstract

Executive function is a cognitive domain with sizable heritability representing higher-order cognitive abilities. Genome-wide association studies (GWAS) of executive function are sparse, particularly in populations underrepresented in medical research. We performed a GWAS on a composite measure of executive function that included measures of mental flexibility and reasoning using data from the Northern Manhattan Study, a racially and ethnically diverse cohort (N = 1077, 69% Hispanic, 17% non-Hispanic Black and 14% non-Hispanic White). Four SNPs located in the long intergenic non-protein coding RNA 1362 gene, LINC01362, on chromosome 1p31.1, were significantly associated with the composite measure of executive function in this cohort (top SNP rs2788328, ß = 0.22, p = 3.1 × 10). The associated SNPs have been shown to influence expression of the tubulin tyrosine ligase like 7 gene, TTLL7 and the protein kinase CAMP-activated catalytic subunit beta gene, PRKACB, in several regions of the brain involved in executive function. Together, these findings present new insight into the genetic underpinnings of executive function in an understudied population.

摘要

执行功能是认知领域的一个重要分支,具有相当大的遗传率,代表着更高阶的认知能力。执行功能的全基因组关联研究(GWAS)相对较少,特别是在医学研究中代表性不足的人群中。我们使用来自北方曼哈顿研究(Northern Manhattan Study)的数据,对执行功能的综合衡量标准进行了 GWAS 分析,该研究是一个种族和民族多样化的队列(N=1077,69%为西班牙裔,17%为非西班牙裔黑人,14%为非西班牙裔白人),包括心理灵活性和推理的衡量标准。四个位于染色体 1p31.1 上的长基因间非蛋白编码 RNA 1362 基因(LINC01362)中的 SNP 与该队列的执行功能综合衡量标准显著相关(位于榜首的 SNP rs2788328,ß=0.22,p=3.1×10)。这些相关的 SNP 已被证明会影响脑内几个与执行功能相关区域中微管酪氨酸连接酶样 7 基因(TTLL7)和蛋白激酶 CAMP 激活的催化亚基β基因(PRKACB)的表达。综上所述,这些发现为研究人群中执行功能的遗传基础提供了新的见解。

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