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

Jing Dong, Annah Wyss, Jingyun Yang, T. Ryan Price, Aude Nicolas, Michael Nalls, Greg Tranah, Nora Franceschini, Zongli Xu, Claudia Schulte, Alvaro Alonso, Steven R. Cummings, Myriam Fornage, Dmitri Zaykin, Leping Li, Xuemei Huang, Stephen Kritchevsky, Yongmei Liu, Thomas Gasser, Robert S. WilsonPhilip L. De Jager, Andrew B. Singleton, Jayant M. Pinto, Tamara Harris, Thomas H. Mosley, David A. Bennett, Stephanie London, Lei Yu, Honglei Chen

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)8021-8032
Number of pages12
JournalMolecular Neurobiology
Volume54
Issue number10
DOIs
StatePublished - Dec 1 2017

Fingerprint

Smell
Genome-Wide Association Study
African Americans
Neurodegenerative Diseases
Prodromal Symptoms
Population
Parkinson Disease
Meta-Analysis
Epilepsy
Schizophrenia
Alzheimer Disease
Genome

All Science Journal Classification (ASJC) codes

  • Neuroscience (miscellaneous)
  • Neurology
  • Cellular and Molecular Neuroscience

Cite this

Dong, Jing ; Wyss, Annah ; Yang, Jingyun ; Price, T. Ryan ; Nicolas, Aude ; Nalls, Michael ; Tranah, Greg ; Franceschini, Nora ; Xu, Zongli ; Schulte, Claudia ; Alonso, Alvaro ; Cummings, Steven R. ; Fornage, Myriam ; Zaykin, Dmitri ; Li, Leping ; Huang, Xuemei ; Kritchevsky, Stephen ; Liu, Yongmei ; Gasser, Thomas ; Wilson, Robert S. ; De Jager, Philip L. ; Singleton, Andrew B. ; Pinto, Jayant M. ; Harris, Tamara ; Mosley, Thomas H. ; Bennett, David A. ; London, Stephanie ; Yu, Lei ; Chen, Honglei. / 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. In: Molecular Neurobiology. 2017 ; Vol. 54, No. 10. pp. 8021-8032.
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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.",
author = "Jing Dong and Annah Wyss and Jingyun Yang and Price, {T. Ryan} and Aude Nicolas and Michael Nalls and Greg Tranah and Nora Franceschini and Zongli Xu and Claudia Schulte and Alvaro Alonso and Cummings, {Steven R.} and Myriam Fornage and Dmitri Zaykin and Leping Li and Xuemei Huang and Stephen Kritchevsky and Yongmei Liu and Thomas Gasser and Wilson, {Robert S.} and {De Jager}, {Philip L.} and Singleton, {Andrew B.} and Pinto, {Jayant M.} and Tamara Harris and Mosley, {Thomas H.} and Bennett, {David A.} and Stephanie London and Lei Yu and Honglei Chen",
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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 2017, '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', Molecular Neurobiology, vol. 54, no. 10, pp. 8021-8032. https://doi.org/10.1007/s12035-016-0282-8

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. / Dong, Jing; Wyss, Annah; Yang, Jingyun; Price, T. Ryan; Nicolas, Aude; Nalls, Michael; Tranah, Greg; Franceschini, Nora; Xu, Zongli; Schulte, Claudia; Alonso, Alvaro; Cummings, Steven R.; Fornage, Myriam; Zaykin, Dmitri; Li, Leping; Huang, Xuemei; Kritchevsky, Stephen; Liu, Yongmei; Gasser, Thomas; Wilson, Robert S.; De Jager, Philip L.; Singleton, Andrew B.; Pinto, Jayant M.; Harris, Tamara; Mosley, Thomas H.; Bennett, David A.; London, Stephanie; Yu, Lei; Chen, Honglei.

In: Molecular Neurobiology, Vol. 54, No. 10, 01.12.2017, p. 8021-8032.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genome-Wide Association Analysis of the Sense of Smell in U.S. Older Adults

T2 - Identification of Novel Risk Loci in African-Americans and European-Americans

AU - Dong, Jing

AU - Wyss, Annah

AU - Yang, Jingyun

AU - Price, T. Ryan

AU - Nicolas, Aude

AU - Nalls, Michael

AU - Tranah, Greg

AU - Franceschini, Nora

AU - Xu, Zongli

AU - Schulte, Claudia

AU - Alonso, Alvaro

AU - Cummings, Steven R.

AU - Fornage, Myriam

AU - Zaykin, Dmitri

AU - Li, Leping

AU - Huang, Xuemei

AU - Kritchevsky, Stephen

AU - Liu, Yongmei

AU - Gasser, Thomas

AU - Wilson, Robert S.

AU - De Jager, Philip L.

AU - Singleton, Andrew B.

AU - Pinto, Jayant M.

AU - Harris, Tamara

AU - Mosley, Thomas H.

AU - Bennett, David A.

AU - London, Stephanie

AU - Yu, Lei

AU - Chen, Honglei

PY - 2017/12/1

Y1 - 2017/12/1

N2 - 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.

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