Genetic variation across the human olfactory receptor repertoire alters odor perception

Author(s)

Trimmer, C. ^[1] ; Keller, A. ^[2] ; Murphy, N. R. ^[1] ; Snyder, L. L. ^[1] ; Willer, J. R. ^[3] ; Nagai, M. H. ^{[4, 5]} ; Katsanis, N. ^[3] ; Vosshall, L. B. ^{[2, 6, 7]} ; Matsunami, H. ^{[4, 8, 9]} ; Mainland, J. D. ^{[1, 10]}

Affiliation

^[1] Monell Chem Senses Ctr, 3500 Market St, Philadelphia, PA 19104 - USA

^[2] Rockefeller Univ, Lab Neurogenet & Behav, New York, NY 10065 - USA

^[3] Duke Univ, Med Ctr, Ctr Human Dis Modeling, Durham, NC 27710 - USA

^[4] Duke Univ, Med Ctr, Dept Mol Genet & Microbiol, Durham, NC 27710 - USA

^[5] Univ Sao Paulo, Dept Biochem, BR-03178200 Sao Paulo - Brazil

^[6] Rockefeller Univ, Howard Hughes Med Inst, New York, NY 10065 - USA

^[7] Rockefeller Univ, Kavli Neural Syst Inst, New York, NY 10065 - USA

^[8] Duke Univ, Dept Neurobiol, Durham, NC 27710 - USA

^[9] Duke Univ, Duke Inst Brain Sci, Durham, NC 27710 - USA

^[10] Univ Penn, Sch Med, Dept Neurosci, Philadelphia, PA 19104 - USA

• Document type: Journal article
• Source: PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA; v. 116, n. 19, p. 9475-9480, MAY 7 2019.
• Web of Science Citations: 5

Abstract

Humans use a family of more than 400 olfactory receptors (ORs) to detect odors, but there is currently no model that can predict olfactory perception from receptor activity patterns. Genetic variation in human ORs is abundant and alters receptor function, allowing us to examine the relationship between receptor function and perception. We sequenced the OR repertoire in 332 individuals and examined how genetic variation affected 276 olfactory phenotypes, including the perceived intensity and pleasantness of 68 odorants at two concentrations, detection thresholds of three odorants, and general olfactory acuity. Genetic variation in a single OR was frequently associated with changes in odorant perception, and we validated 10 cases in which in vitro OR function correlated with in vivo odorant perception using a functional assay. In 8 of these 10 cases, reduced receptor function was associated with reduced intensity perception. In addition, we used participant genotypes to quantify genetic ancestry and found that, in combination with single OR genotype, age, and gender, we can explain between 10% and 20% of the perceptual variation in 15 olfactory phenotypes, highlighting the importance of single OR genotype, ancestry, and demographic factors in the variation of olfactory perception. (AU)

• FAPESP's process: 17/00726-2 - Study of Ric-8B's function in mTOR activation by using an olfactory model
• Grantee: Maíra Harume Nagai
• Support type: Scholarships abroad - Research Internship - Post-doctor