title: 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.
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.
authors.affiliation: 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, USA. dongj4@mail.nih.gov.
authors.forename: Jing
authors.initials: J
authors.lastname: Dong
authors.affiliation: 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, USA.
authors.forename: Annah
authors.initials: A
authors.lastname: Wyss
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Jingyun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
authors.forename: T Ryan
authors.initials: TR
authors.lastname: Price
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Aude
authors.initials: A
authors.lastname: Nicolas
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Nalls
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA, USA.
authors.forename: Greg
authors.initials: G
authors.lastname: Tranah
authors.affiliation: Department of Epidemiology, University of North Carolina Gillings School of Global Public Health, Chapel Hill, NC, USA.
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.affiliation: 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, USA.
authors.forename: Zongli
authors.initials: Z
authors.lastname: Xu
authors.affiliation: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Schulte
authors.affiliation: Department of Epidemiology, Rollins School of Public Health, Emory University, Atlanta, GA, USA.
authors.forename: Alvaro
authors.initials: A
authors.lastname: Alonso
authors.affiliation: California Pacific Medical Center Research Institute, San Francisco, CA, USA.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Cummings
authors.affiliation: Institute of Molecular Medicine and Human Genetics Center, University of Texas Health Science Center at Houston, Houston, TX, USA.
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Dmitri
authors.initials: D
authors.lastname: Zaykin
authors.affiliation: Biostatistics Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.
authors.forename: Leping
authors.initials: L
authors.lastname: Li
authors.affiliation: Pennsylvania State University-Milton S. Hershey Medical Center, Hershey, PA, USA.
authors.forename: Xuemei
authors.initials: X
authors.lastname: Huang
authors.affiliation: Sticht Center on Aging, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Kritchevsky
authors.affiliation: Division of Public Health Sciences, Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors.forename: Yongmei
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department for Neurodegenerative Diseases, Hertie Institute for Clinical Brain Research, University of Tübingen, Tübingen, Germany.|Genome Biology for Neurodegenerative Diseases, German Center for Neurodegenerative Diseases (DZNE), Tübingen, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Gasser
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wilson
authors.affiliation: Program in Translational Neuro Psychiatric Genomics, Institute for the Neurosciences, Departments of Neurology and Psychiatry, Brigham and Women's Hospital; Harvard Medical School; Program in Medical and Population Genetics, Broad Institute, Boston, MA, USA.
authors.forename: Philip L
authors.initials: PL
authors.lastname: De Jager
authors.affiliation: Laboratory of Neurogenetics, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Andrew B
authors.initials: AB
authors.lastname: Singleton
authors.affiliation: Section of Otolaryngology-Head and Neck Surgery, Department of Surgery, The University of Chicago Medicine and Biological Sciences, Chicago, IL, USA.
authors.forename: Jayant M
authors.initials: JM
authors.lastname: Pinto
authors.affiliation: Laboratory of Epidemiology, Demography, and Biometry, National Institute on Aging, Bethesda, MD, USA.
authors.forename: Tamara
authors.initials: T
authors.lastname: Harris
authors.affiliation: Division of Geriatrics, Department of Medicine, University of Mississippi Medical Center, Jackson, MS, USA.
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: David A
authors.initials: DA
authors.lastname: Bennett
authors.affiliation: 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, USA.
authors.forename: Stephanie
authors.initials: S
authors.lastname: London
authors.affiliation: Rush Alzheimer's Disease Center, Rush University Medical Center, Chicago, IL, USA.
authors.forename: Lei
authors.initials: L
authors.lastname: Yu
authors.affiliation: 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, USA.
authors.forename: Honglei
authors.initials: H
authors.lastname: Chen
mesh_terms: D001741:Black or African American; D000368:Aged; D000375:Aging; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D000090062:Kruppel-Like Factor 4; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012306:Risk; D012903:Smell / Q000235:genetics*; D014481:United States; D044465:White People
keywords: African-American; GWAS; The sense of smell