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

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^-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.

Keywords: Cognition; Executive function; GWAS; Genetic association; Minority populations.

Fig. 1.

Manhattan Plot depicting results from the genome-wide executive function meta-analysis. The red line indicates the genome-wide significance threshold of p < 5.0 × 10⁻⁸. The R package “qqman” was used to generate the Manhattan Plot.