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. Mol Neurobiol 2017 Dec;54(10):8021-8032
Date
11/24/2016Pubmed ID
27878761Pubmed Central ID
PMC5441979DOI
10.1007/s12035-016-0282-8Scopus ID
2-s2.0-84996879781 (requires institutional sign-in at Scopus site) 13 CitationsAbstract
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.
Author List
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 Jr, Bennett DA, London S, Yu L, Chen HAuthor
Jing Dong PhD Assistant Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AgedAging
Female
Genetic Predisposition to Disease
Genome-Wide Association Study
Genotype
Humans
Male
Polymorphism, Single Nucleotide
Risk
Smell
United States
