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Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution.
PeerJ. 2020; 8:e9145.P

Abstract

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 (βOP), offspring-midparent (βOM), and full-sib regression slopes (βFS). Nonparametric significance levels were obtained from 1,000 bootstrap samples. βOPs were used as simple indicators of quantile-specific heritability (i.e., h 2 = 2βOP/(1+rspouse), where rspouse was the correlation between spouses).

Results

βOP ± 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., βOP ± 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.

Authors+Show Affiliations

Molecular Biophysics & Integrated Bioimaging, Lawrence Berkeley National Laboratory, Berkeley, CA, United States of America.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32461834

Citation

Williams, Paul T.. "Spirometric Traits Show Quantile-dependent Heritability, Which May Contribute to Their Gene-environment Interactions With Smoking and Pollution." PeerJ, vol. 8, 2020, pp. e9145.
Williams PT. Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution. PeerJ. 2020;8:e9145.
Williams, P. T. (2020). Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution. PeerJ, 8, e9145. https://doi.org/10.7717/peerj.9145
Williams PT. Spirometric Traits Show Quantile-dependent Heritability, Which May Contribute to Their Gene-environment Interactions With Smoking and Pollution. PeerJ. 2020;8:e9145. PubMed PMID: 32461834.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Spirometric traits show quantile-dependent heritability, which may contribute to their gene-environment interactions with smoking and pollution. A1 - Williams,Paul T, Y1 - 2020/05/15/ PY - 2019/10/23/received PY - 2020/04/17/accepted PY - 2020/5/29/entrez PY - 2020/5/29/pubmed PY - 2020/5/29/medline KW - COPD KW - Forced vital capacity KW - Gene environment interaction KW - Heritability KW - Pollution KW - Pulmonary function KW - Quantile dependent expressivity KW - SERPINA1 KW - Smoking KW - Spirometric data SP - e9145 EP - e9145 JF - PeerJ VL - 8 N2 - 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 (βOP), offspring-midparent (βOM), and full-sib regression slopes (βFS). Nonparametric significance levels were obtained from 1,000 bootstrap samples. βOPs were used as simple indicators of quantile-specific heritability (i.e., h 2 = 2βOP/(1+rspouse), where rspouse was the correlation between spouses). Results: βOP ± 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., βOP ± 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. SN - 2167-8359 UR - https://www.unboundmedicine.com/medline/citation/32461834/Spirometric_traits_show_quantile_dependent_heritability_which_may_contribute_to_their_gene_environment_interactions_with_smoking_and_pollution_ L2 - https://doi.org/10.7717/peerj.9145 DB - PRIME DP - Unbound Medicine ER -
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