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

Executive function is a cognitive domain with sizable heritability representing higher-order cognitive abil-ities. Genome-wide association studies (GWAS) of executive function are sparse, particularly in popula-tions 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 Man-hattan 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 x 10-10 ). 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 ex-ecutive function. Together, these findings present new insight into the genetic underpinnings of executive function in an understudied population. (c) 2022 Elsevier Inc. All rights reserved.

Automated summary

This study conducted a genome-wide association study on executive function in a racially and ethnically diverse cohort. They identified several SNPs in the LINC01362 gene on chromosome 1p31.1 that were significantly associated with executive function. These SNPs were found to influence the expression of genes involved in executive function in various regions of the brain.