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Author Notes:

Dr. Jing Dong, Epidemiology Branch, National Institute of Environmental Health Sciences, 111 T.W. Alexander Dr. P.O. Box 12233, Mail drop A3-05, Research Triangle Park, NC 27709. Tel: 919-541-5713. dongj4@mail.nih.gov.

The authors thank the staff and participants of the ARIC study, Health ABC study, and the ROS/MAP for their important contributions.

The authors declare no competing financial interests.

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Research Funding:

The Atherosclerosis Risk in Communities Study is carried out as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN268201100012C), R01HL087641, R01HL59367 and R01HL086694, with the ARIC carotid MRI examination funded by U01HL075572-01; National Human Genome Research Institute contract U01HG004402; and National Institutes of Health contract HHSN268200625226C. Neurocognitive data is collected by U01 HL096812, HL096814, HL096899, HL096902, and HL096917 with previous brain MRI examinations funded by R01-HL70825. Infrastructure was partly supported by Grant Number UL1RR025005, a component of the National Institutes of Health and NIH Roadmap for Medical Research. Additional support for this project includes grants R01-HL093029 and R01-NS087541.

The Health ABC Study research was supported by in part by the Intramural Research Program of the NIH, National Institute on Aging (NIA) and by NIA contracts N01AG62101, N01AG62103, and N01AG62106. The genome-wide association study was funded by NIA grant 1R01AG032098-01A1 to Wake Forest University Health Sciences and genotyping services were provided by the Center for Inherited Disease Research (CIDR). CIDR is fully funded through a federal contract from the National Institutes of Health to The Johns Hopkins University, contract number HHSN268200782096C.

The Religious Orders Study and Rush Memory and Aging Project were supported by grants from the National Institutes of Aging [R01 AG30146, P30 AG10161, R01 AG17917, R01 AG15819], the Illinois Department of Public Health, and the Translational Genomics Research Institute.

JMP was supported by the National Institute on Aging (K23 AG036762), the McHugh Otolaryngology Research Fund, the American Geriatrics Society, The Center on the Demography and Economics of Aging, and the Institute of Translational Medicine at The University of Chicago (KL2RR025000 and UL1RR024999).

Keywords:

  • Science & Technology
  • Life Sciences & Biomedicine
  • Neurosciences
  • Neurosciences & Neurology
  • GWAS
  • The sense of smell
  • African-American
  • PARKINSONS-DISEASE
  • ALZHEIMERS-DISEASE
  • ODOR IDENTIFICATION
  • OLFACTORY FUNCTION
  • SCHIZOPHRENIA
  • METAANALYSIS
  • IMPAIRMENT
  • EXPRESSION
  • CORTEX
  • SCANS

Genome-Wide Association Analysis of the Sense of Smell in US Older Adults: Identification of Novel Risk Loci in African-Americans and European-Americans

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Journal Title:

Molecular Neurobiology

Volume:

Volume 54, Number 10

Publisher:

, Pages 8021-8032

Type of Work:

Article | Post-print: After Peer Review

Abstract:

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.

Copyright information:

© 2016, Springer Science+Business Media New York (outside the USA).

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