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

• Published in: Neurobiology of aging 2023-03, Vol.123, p.216-221
• Main Authors: Dueker, Nicole, Wang, Liyong, Gardener, Hannah, Gomez, Lissette, Kaur, Sonya, Beecham, Ashley, Blanton, Susan H., Dong, Chuanhui, Gutierrez, Jose, Cheung, Ying Kuen, Moon, Yeseon P., Levin, Bonnie, Wright, Clinton B., Elkind, Mitchell S.V., Sacco, Ralph L., Rundek, Tatjana
• Format: Article
• Language: English
• Subjects: Black or African American; Brain; Cognition; Cognition - physiology; Executive Function; Genetic association; Genome-Wide Association Study; GWAS; Hispanic or Latino; Humans; Minority populations; Polymorphism, Single Nucleotide - genetics
• ISSN: 0197-4580; 1558-1497
• DOI: 10.1016/j.neurobiolaging.2022.11.016

•Four SNPs in LINC01362 are associated with executive function in a diverse cohort.•The SNPs are associated with color trails test form 2, odd-man-out subtests 2 and 4.•Identified SNPs influence expression of TTLL7 and PRKACB in several brain regions. 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.