Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution

Journal Article · Fri May 15 00:00:00 EDT 2020 · PeerJ

DOI:https://doi.org/10.7717/peerj.9145· OSTI ID:1816115

Williams, Paul T. ^[1]

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1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Molecular Biophysics & Integrated Bioimaging; OSTI

Background: “Quantile-dependent expressivity” refers to a genetic effect that is dependent upon whether the phenotype (e.g., spirometric data) is high or low relative to its population distribution. Forced vital capacity (FVC), forced expiratory volume in 1 second (FEV₁), and the FEV₁/FVC ratio are moderately heritable spirometric traits. The aim of the analyses is to test whether their heritability (h²) is constant over all quantiles of their distribution. Methods: Quantile regression was applied to the mean age, sex, height and smoking-adjusted spirometric data over multiple visits in 9,993 offspring-parent pairs and 1,930 sibships from the Framingham Heart Study to obtain robust estimates of offspring-parent (β_OP), offspring-midparent (β_OM), and full-sib regression slopes (β_FS). Nonparametric significance levels were obtained from 1,000 bootstrap samples. β_OPs were used as simple indicators of quantile-specific heritability (i.e.,h² = 2β_OP/(1+r_spouse), where r_spousewas the correlation between spouses). Results: β_OP ± standard error (SE) decreased by 0.0009 ± 0.0003 (P = 0.003) with every one-percent increment in the population distribution of FEV₁/FVC, i.e., β_OP ± SE were: 0.182 ± 0.031, 0.152 ± 0.015; 0.136 ± 0.011; 0.121 ± 0.013; and 0.099 ± 0.013 at the 10th, 25th, 50th, 75th, and 90th percentiles of the FEV₁/FVC distribution, respectively. These correspond to h² ± SEs of 0.350 ± 0.060 at the 10th, 0.292 ± 0.029 at the 25th, 0.262 ± 0.020 at the 50th, 0.234 ± 0.025 at the 75th, and 0.191 ± 0.025 at the 90th percentiles of the FEV₁/FVC ratio. Maximum mid-expiratory flow (MMEF) h² ± SEs increased 0.0025 ± 0.0007 (P = 0.0004) with every one-percent increment in its distribution, i.e.: 0.467 ± 0.046, 0.467 ± 0.033, 0.554 ± 0.038, 0.615 ± 0.042, and 0.675 ± 0.060 at the 10th, 25th, 50th, 75th, and 90th percentiles of its distribution. This was due to forced expiratory flow at 75% of FVC (FEF75%), whose quantile-specific h² increased an average of 0.0042 ± 0.0008 for every one-percent increment in its distribution. It is speculated that previously reported gene-environment interactions may be partially attributable to quantile-specific h², i.e., greater heritability in individuals with lower FEV₁/FVC due to smoking or airborne particles exposure vs. nonsmoking, unexposed individuals. Conclusion: Heritabilities of FEV₁/FVC, MMEF, and FEF75% from quantile-regression of offspring-parent and sibling spirometric data suggest their quantile-dependent expressivity.

• Research Organization: Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)
• Sponsoring Organization: National Heart, Lung, and Blood Institute; USDOE Office of Science (SC)
• Grant/Contract Number: AC02-05CH11231
• OSTI ID: 1816115
• Journal Information: PeerJ, Journal Name: PeerJ Vol. 8; ISSN 2167-8359
• Publisher: PeerJ Inc.
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
71 CLASSICAL AND QUANTUM MECHANICS
GENERAL PHYSICS
COPD
SERPINA1
forced vital capacity
gene environment interaction
genetics
heritability
medical genetics
pollution
public health
pulmonary function
quantile dependent expressivity
respiratory medicine
smoking
spirometric data