Journal
MOLECULAR NEUROBIOLOGY
Volume 54, Issue 10, Pages 8021-8032Publisher
SPRINGER
DOI: 10.1007/s12035-016-0282-8
Keywords
GWAS; The sense of smell; African-American
Categories
Funding
- NIH [Z01 ES101986]
- National Institute of Environmental Health Sciences
- National Heart, Lung, and Blood Institute [HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, HHSN268201100012C, R01HL087641, R01HL59367, R01HL086694]
- National Human Genome Research Institute [U01HG004402]
- National Institutes of Health [HHSN268200625226C, UL1RR025005]
- NIH Roadmap for Medical Research
- Intramural Research Program of the NIH, National Institute on Aging (NIA)
- NIA [N01AG62101, N01AG62103, N01AG62106]
- NIA grant [1R01AG032098-01A1]
- federal contract from the National Institutes of Health [HHSN268200782096C]
- National Institutes of Aging [R01 AG30146, P30 AG10161, R01 AG17917, R01 AG15819]
- Illinois Department of Public Health
- Translational Genomics Research Institute
- National Institute on Aging [K23 AG036762]
- McHugh Otolaryngology Research Fund
- American Geriatrics Society
- Center on the Demography and Economics of Aging
- Institute of Translational Medicine at The University of Chicago [KL2RR025000, UL1RR024999]
- [R01-HL70825]
- [U01HL075572-01]
- [R01-HL093029]
- [R01-NS087541]
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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 x 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.
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