Genome-wide meta-analysis on the sense of smell among US older adults

Jing Dong, Jingyun Yang, Greg Tranah, Nora Franceschini, Neeta Parimi, Gorka Alkorta-Aranburu, Zongli Xu, Alvaro Alonso, Steven R. Cummings, Myriam Fornage, Xuemei Huang, Stephen Kritchevsky, Yongmei Liu, Stephanie London, Liang Niu, Robert S. Wilson, Philip L. De Jager, Lei Yu, Andrew B. Singleton, Tamara HarrisThomas H. Mosley, Jayant M. Pinto, David A. Bennett, Honglei Chen

Research output: Contribution to journalArticle

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Abstract

Olfactory dysfunction is common among older adults and affects their safety, nutrition, quality of life, and mortality. More importantly, the decreased sense of smell is an early symptom of neurodegenerative diseases such as Parkinson disease (PD) and Alzheimer disease. However, the genetic determinants for the sense of smell have been poorly investigated. We here performed the first genome-wide meta-analysis on the sense of smell among 6252 US older adults of European descent from the Atherosclerosis Risk in Communities (ARIC) study, the Health, Aging, and Body Composition (Health ABC) study, and the Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP). Genome-wide association study analysis was performed first by individual cohorts and then meta-analyzed using fixed-effect models with inverse variance weights. Although no SNPs reached genome-wide statistical significance, we identified 13 loci with suggestive evidence for an association with the sense of smell (Pmeta<1×10-5). Of these, 2 SNPs at chromosome 17q21.31 (rs199443 in NSF, P=3.02×10-6; and rs2732614 in KIAA1267-LRRC37A, P=6.65×10-6) exhibited cis effects on the expression of microtubule-associated protein tau (MAPT, 17q21.31) in 447 frontal-cortex samples obtained postmortem and profiled by RNAseq (P<1×10-15). Gene-based and pathway-enrichment analyses further implicated MAPT in regulating the sense of smell in older adults. Similar results were obtained after excluding participants who reported a physician-diagnosed PD or use of PD medications. In conclusion, we provide preliminary evidence that the MAPT locus may play a role in regulating the sense of smell in older adults and therefore offer a potential genetic link between poor sense of smell and major neurodegenerative diseases.

Original languageEnglish (US)
Pages (from-to)e1892
JournalMedicine (United States)
Volume94
Issue number47
DOIs
StatePublished - Nov 2015

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Smell
Meta-Analysis
Genome
Parkinson Disease
Genome-Wide Association Study
Neurodegenerative Diseases
Single Nucleotide Polymorphism
Microtubule-Associated Proteins
Frontal Lobe
Body Composition
Atherosclerosis
Alzheimer Disease
Chromosomes
Quality of Life
Physicians
Safety
Weights and Measures
Mortality
Health
Genes

All Science Journal Classification (ASJC) codes

  • Medicine(all)

Cite this

Dong, J., Yang, J., Tranah, G., Franceschini, N., Parimi, N., Alkorta-Aranburu, G., ... Chen, H. (2015). Genome-wide meta-analysis on the sense of smell among US older adults. Medicine (United States), 94(47), e1892. https://doi.org/10.1097/MD.0000000000001892
Dong, Jing ; Yang, Jingyun ; Tranah, Greg ; Franceschini, Nora ; Parimi, Neeta ; Alkorta-Aranburu, Gorka ; Xu, Zongli ; Alonso, Alvaro ; Cummings, Steven R. ; Fornage, Myriam ; Huang, Xuemei ; Kritchevsky, Stephen ; Liu, Yongmei ; London, Stephanie ; Niu, Liang ; Wilson, Robert S. ; De Jager, Philip L. ; Yu, Lei ; Singleton, Andrew B. ; Harris, Tamara ; Mosley, Thomas H. ; Pinto, Jayant M. ; Bennett, David A. ; Chen, Honglei. / Genome-wide meta-analysis on the sense of smell among US older adults. In: Medicine (United States). 2015 ; Vol. 94, No. 47. pp. e1892.
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abstract = "Olfactory dysfunction is common among older adults and affects their safety, nutrition, quality of life, and mortality. More importantly, the decreased sense of smell is an early symptom of neurodegenerative diseases such as Parkinson disease (PD) and Alzheimer disease. However, the genetic determinants for the sense of smell have been poorly investigated. We here performed the first genome-wide meta-analysis on the sense of smell among 6252 US older adults of European descent from the Atherosclerosis Risk in Communities (ARIC) study, the Health, Aging, and Body Composition (Health ABC) study, and the Religious Orders Study and the Rush Memory and Aging Project (ROS/MAP). Genome-wide association study analysis was performed first by individual cohorts and then meta-analyzed using fixed-effect models with inverse variance weights. Although no SNPs reached genome-wide statistical significance, we identified 13 loci with suggestive evidence for an association with the sense of smell (Pmeta<1×10-5). Of these, 2 SNPs at chromosome 17q21.31 (rs199443 in NSF, P=3.02×10-6; and rs2732614 in KIAA1267-LRRC37A, P=6.65×10-6) exhibited cis effects on the expression of microtubule-associated protein tau (MAPT, 17q21.31) in 447 frontal-cortex samples obtained postmortem and profiled by RNAseq (P<1×10-15). Gene-based and pathway-enrichment analyses further implicated MAPT in regulating the sense of smell in older adults. Similar results were obtained after excluding participants who reported a physician-diagnosed PD or use of PD medications. In conclusion, we provide preliminary evidence that the MAPT locus may play a role in regulating the sense of smell in older adults and therefore offer a potential genetic link between poor sense of smell and major neurodegenerative diseases.",
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Dong, J, Yang, J, Tranah, G, Franceschini, N, Parimi, N, Alkorta-Aranburu, G, Xu, Z, Alonso, A, Cummings, SR, Fornage, M, Huang, X, Kritchevsky, S, Liu, Y, London, S, Niu, L, Wilson, RS, De Jager, PL, Yu, L, Singleton, AB, Harris, T, Mosley, TH, Pinto, JM, Bennett, DA & Chen, H 2015, 'Genome-wide meta-analysis on the sense of smell among US older adults', Medicine (United States), vol. 94, no. 47, pp. e1892. https://doi.org/10.1097/MD.0000000000001892

Genome-wide meta-analysis on the sense of smell among US older adults. / Dong, Jing; Yang, Jingyun; Tranah, Greg; Franceschini, Nora; Parimi, Neeta; Alkorta-Aranburu, Gorka; Xu, Zongli; Alonso, Alvaro; Cummings, Steven R.; Fornage, Myriam; Huang, Xuemei; Kritchevsky, Stephen; Liu, Yongmei; London, Stephanie; Niu, Liang; Wilson, Robert S.; De Jager, Philip L.; Yu, Lei; Singleton, Andrew B.; Harris, Tamara; Mosley, Thomas H.; Pinto, Jayant M.; Bennett, David A.; Chen, Honglei.

In: Medicine (United States), Vol. 94, No. 47, 11.2015, p. e1892.

Research output: Contribution to journalArticle

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T1 - Genome-wide meta-analysis on the sense of smell among US older adults

AU - Dong, Jing

AU - Yang, Jingyun

AU - Tranah, Greg

AU - Franceschini, Nora

AU - Parimi, Neeta

AU - Alkorta-Aranburu, Gorka

AU - Xu, Zongli

AU - Alonso, Alvaro

AU - Cummings, Steven R.

AU - Fornage, Myriam

AU - Huang, Xuemei

AU - Kritchevsky, Stephen

AU - Liu, Yongmei

AU - London, Stephanie

AU - Niu, Liang

AU - Wilson, Robert S.

AU - De Jager, Philip L.

AU - Yu, Lei

AU - Singleton, Andrew B.

AU - Harris, Tamara

AU - Mosley, Thomas H.

AU - Pinto, Jayant M.

AU - Bennett, David A.

AU - Chen, Honglei

PY - 2015/11

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Dong J, Yang J, Tranah G, Franceschini N, Parimi N, Alkorta-Aranburu G et al. Genome-wide meta-analysis on the sense of smell among US older adults. Medicine (United States). 2015 Nov;94(47):e1892. https://doi.org/10.1097/MD.0000000000001892