Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans.
Journal Article (Journal Article)
The human sense of smell decreases with age, and a poor sense of smell are among the most important prodromal symptoms of several neurodegenerative diseases. Recent evidence further suggests a racial difference in the sense of smell among U.S. older adults. However, no genome-wide association study (GWAS) on the sense of smell has been conducted in African-Americans (AAs). We performed the first genome-wide meta-analysis of the sense of smell among 1979 AAs and 6582 European-Americans (EAs) from three U.S. aging cohorts. In the AA population, we identified nine novel regions (KLF4-ACTL7B, RAPGEF2-FSTL5, TCF4-LOC100505474, PCDH10, KIAA1751, MYO5B, MIR320B1-CD2, NR5A2-LINC00862, SALL1-C16orf97) that were associated with the sense of smell (P < 5 × 10-8). Many of these regions have been previously linked to neuropsychiatric (schizophrenia or epilepsy) or neurodegenerative (Parkinson's or Alzheimer's disease) diseases associated with a decreased sense of smell. In the EA population, we identified two novel loci in or near RASGRP1 and ANXA2P3 associated with sense of smell. In conclusion, this study identified several ancestry-specific loci that are associated with the sense of smell in older adults. While these findings need independent confirmation, they may lead to novel insights into the biology of the sense of smell in older adults and its relationships to neuropsychological and neurodegenerative diseases.
Full Text
Duke Authors
Cited Authors
- Dong, J; Wyss, A; Yang, J; Price, TR; Nicolas, A; Nalls, M; Tranah, G; Franceschini, N; Xu, Z; Schulte, C; Alonso, A; Cummings, SR; Fornage, M; Zaykin, D; Li, L; Huang, X; Kritchevsky, S; Liu, Y; Gasser, T; Wilson, RS; De Jager, PL; Singleton, AB; Pinto, JM; Harris, T; Mosley, TH; Bennett, DA; London, S; Yu, L; Chen, H
Published Date
- December 2017
Published In
Volume / Issue
- 54 / 10
Start / End Page
- 8021 - 8032
PubMed ID
- 27878761
Pubmed Central ID
- PMC5441979
Electronic International Standard Serial Number (EISSN)
- 1559-1182
Digital Object Identifier (DOI)
- 10.1007/s12035-016-0282-8
Language
- eng
Conference Location
- United States