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

Nicole Dueker; Liyong Wang; Hannah Gardener; Lissette Gomez; Sonya Kaur; Ashley Beecham; Susan H Blanton; Chuanhui Dong; Jose Gutierrez; Ying Kuen Cheung; Yeseon P Moon; Bonnie Levin; Clinton B Wright; Mitchell S V Elkind; Ralph L Sacco; Tatjana Rundek

doi:10.1016/j.neurobiolaging.2022.11.016

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

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

Authors

Affiliations

¹ John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA. Electronic address: ndueker@med.miami.edu.
² 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.
³ Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL USA.
⁴ John P. Hussman Institute for Human Genomics, University of Miami, Miami, FL, USA.
⁵ Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL USA; Department of Neurology, Evelyn F. McKnight Brain Institute, University of Miami, Miami FL USA.
⁶ Department of Neurology and the Gertrude H Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY USA.
⁷ Department of Biostatistics, Mailman School of Public Health, Columbia University, New York, NY, USA.
⁸ National Institute of Neurological Disorders and Stroke, Bethesda, MD USA.
⁹ Department of Neurology and the Gertrude H Sergievsky Center, Vagelos College of Physicians and Surgeons, Columbia University, New York, NY USA; Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, NY USA.
¹⁰ Department of Neurology, Miller School of Medicine, University of Miami, Miami, FL USA; Department of Neurology, Evelyn F. McKnight Brain Institute, University of Miami, Miami FL USA; Department of Public Health Sciences, Miller School of Medicine, University of Miami, Miami, FL USA.

PMID: 36658081
PMCID: PMC10064578
DOI: 10.1016/j.neurobiolaging.2022.11.016

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Black or African American
Brain
Cognition / physiology
Executive Function*
Genome-Wide Association Study*
Hispanic or Latino
Humans
Polymorphism, Single Nucleotide / genetics

Grants and funding

R01 NS029993/NS/NINDS NIH HHS/United States