TY - JOUR
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
N1 - Publisher Copyright:
© 2015 Wolters Kluwer Health, Inc. All rights reserved.
PY - 2015/11
Y1 - 2015/11
N2 - 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.
AB - 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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U2 - 10.1097/MD.0000000000001892
DO - 10.1097/MD.0000000000001892
M3 - Article
C2 - 26632684
AN - SCOPUS:84960336218
SN - 0025-7974
VL - 94
SP - e1892
JO - Medicine (United States)
JF - Medicine (United States)
IS - 47
ER -