Aging
Navigate
Submit an Article
Research Paper|Volume 13, Issue 14|pp 18769—18788

An association study in the Taiwan Biobank elicits three novel candidates for cognitive aging in old adults: NCAM1, TTC12 and ZBTB20

Eugene Lin1,2,3, Po-Hsiu Kuo4,5, Wan-Yu Lin4, Yu-Li Liu6, Albert C. Yang7,8, Shih-Jen Tsai9,10
  • 1Department of Biostatistics, University of Washington, Seattle, WA 98195, USA
  • 2Department of Electrical and Computer Engineering, University of Washington, Seattle, WA 98195, USA
  • 3Graduate Institute of Biomedical Sciences, China Medical University, Taichung 40402, Taiwan
  • 4Department of Public Health, Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei 10617, Taiwan
  • 5Department of Psychiatry, National Taiwan University Hospital, Taipei 100, Taiwan
  • 6Center for Neuropsychiatric Research, National Health Research Institutes, Miaoli County 35053, Taiwan
  • 7Division of Interdisciplinary Medicine and Biotechnology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA
  • 8Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
  • 9Department of Psychiatry, Taipei Veterans General Hospital, Taipei 11217, Taiwan
  • 10Division of Psychiatry, National Yang Ming Chiao Tung University, Taipei 112304, Taiwan
Received: April 5, 2021Accepted: July 8, 2021Published: July 20, 2021
https://doi.org/10.18632/aging.203321

Copyright: © 2021 Lin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

The dopamine receptor-related loci have been suggested to be associated with cognitive functions and neurodegenerative diseases. It is unknown whether genetic variants such as single nucleotide polymorphisms (SNPs) in the dopamine receptor-related loci could contribute to cognitive aging independently as well as by virtue of complicated interplays in the elder population. To assess whether SNPs in the dopamine receptor-related loci are associated with cognitive aging in the elder population, we evaluated SNPs in the DRD1, NCAM1-TTC12-ANKK1-DRD2, DRD3-LOC107986115-ZNF80-TIGIT-MIR568-ZBTB20, DRD4, and DRD5-SLC2A9 loci from 25,195 older Taiwanese individuals from the Taiwan Biobank. Mini-Mental State Examination (MMSE) was scrutinized for all participants, where MMSE scores were employed to evaluate cognitive functions. From our analysis, we identified three novel genes for cognitive aging that have not previously been reported: ZBTB20 on chromosome 3 and NCAM1 and TTC12 on chromosome 11. NCAM1 and ZBTB20 are strong candidates for having a role in cognitive aging with mutations in ZBTB20 resulting in intellectual disability, and NCAM1 previously found to be associated with associative memory in humans. Additionally, we found the effects of interplays between physical activity and these three novel genes. Our study suggests that genetic variants in the dopamine receptor-related loci may influence cognitive aging individually and by means of gene-physical activity interactions.