Quantile-Dependent Expressivity of Serum Uric Acid Concentrations

Objective. “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., serum uric acid) is high or low relative to its distribution. Analyses were performed to test whether serum uric acid heritability is quantile-specific and whether...

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Main Author: Paul T. Williams
Format: Article
Language:English
Published: Wiley 2021-01-01
Series:International Journal of Genomics
Online Access:http://dx.doi.org/10.1155/2021/3889278
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author Paul T. Williams
author_facet Paul T. Williams
author_sort Paul T. Williams
collection DOAJ
description Objective. “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., serum uric acid) is high or low relative to its distribution. Analyses were performed to test whether serum uric acid heritability is quantile-specific and whether this could explain some reported gene-environment interactions. Methods. Serum uric acid concentrations were analyzed from 2151 sibships and 12,068 offspring-parent pairs from the Framingham Heart Study. Quantile-specific heritability from offspring-parent regression slopes (βOP,h2=2βOP/1+rspouse) and full-sib regression slopes (βFS,h2=1+8rspouseβFS0.5−1/2rspouse) was robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results. Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s sex- and age-adjusted uric acid distribution when estimated from βOP Ptrend=0.001: 0.34±0.03 at the 10th, 0.36±0.03 at the 25th, 0.41±0.03 at the 50th, 0.46±0.04 at the 75th, and 0.49±0.05 at the 90th percentile and when estimated from βFS Ptrend=0.006. This is consistent with the larger genetic effect size of (1) the SLC2A9 rs11722228 polymorphism in gout patients vs. controls, (2) the ABCG2 rs2231142 polymorphism in men vs. women, (3) the SLC2A9 rs13113918 polymorphism in obese patients prior to bariatric surgery vs. two-year postsurgery following 29 kg weight loss, (4) the ABCG2 rs6855911 polymorphism in obese vs. nonobese women, and (5) the LRP2 rs2544390 polymorphism in heavier drinkers vs. abstainers. Quantile-dependent expressivity may also explain the larger genetic effect size of an SLC2A9/PKD2/ABCG2 haplotype for high vs. low intakes of alcohol, chicken, or processed meats. Conclusions. Heritability of serum uric acid concentrations is quantile-specific.
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spelling doaj-art-be945116cd8e44468b4096e645bdce6c2025-02-03T01:24:47ZengWileyInternational Journal of Genomics2314-436X2314-43782021-01-01202110.1155/2021/38892783889278Quantile-Dependent Expressivity of Serum Uric Acid ConcentrationsPaul T. Williams0Lawrence Berkeley National Laboratory, Molecular Biophysics & Integrated Bioimaging Division, 1 Cyclotron Road, Berkeley, CA 94720, USAObjective. “Quantile-dependent expressivity” occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., serum uric acid) is high or low relative to its distribution. Analyses were performed to test whether serum uric acid heritability is quantile-specific and whether this could explain some reported gene-environment interactions. Methods. Serum uric acid concentrations were analyzed from 2151 sibships and 12,068 offspring-parent pairs from the Framingham Heart Study. Quantile-specific heritability from offspring-parent regression slopes (βOP,h2=2βOP/1+rspouse) and full-sib regression slopes (βFS,h2=1+8rspouseβFS0.5−1/2rspouse) was robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. Results. Quantile-specific h2 (±SE) increased with increasing percentiles of the offspring’s sex- and age-adjusted uric acid distribution when estimated from βOP Ptrend=0.001: 0.34±0.03 at the 10th, 0.36±0.03 at the 25th, 0.41±0.03 at the 50th, 0.46±0.04 at the 75th, and 0.49±0.05 at the 90th percentile and when estimated from βFS Ptrend=0.006. This is consistent with the larger genetic effect size of (1) the SLC2A9 rs11722228 polymorphism in gout patients vs. controls, (2) the ABCG2 rs2231142 polymorphism in men vs. women, (3) the SLC2A9 rs13113918 polymorphism in obese patients prior to bariatric surgery vs. two-year postsurgery following 29 kg weight loss, (4) the ABCG2 rs6855911 polymorphism in obese vs. nonobese women, and (5) the LRP2 rs2544390 polymorphism in heavier drinkers vs. abstainers. Quantile-dependent expressivity may also explain the larger genetic effect size of an SLC2A9/PKD2/ABCG2 haplotype for high vs. low intakes of alcohol, chicken, or processed meats. Conclusions. Heritability of serum uric acid concentrations is quantile-specific.http://dx.doi.org/10.1155/2021/3889278
spellingShingle Paul T. Williams
Quantile-Dependent Expressivity of Serum Uric Acid Concentrations
International Journal of Genomics
title Quantile-Dependent Expressivity of Serum Uric Acid Concentrations
title_full Quantile-Dependent Expressivity of Serum Uric Acid Concentrations
title_fullStr Quantile-Dependent Expressivity of Serum Uric Acid Concentrations
title_full_unstemmed Quantile-Dependent Expressivity of Serum Uric Acid Concentrations
title_short Quantile-Dependent Expressivity of Serum Uric Acid Concentrations
title_sort quantile dependent expressivity of serum uric acid concentrations
url http://dx.doi.org/10.1155/2021/3889278
work_keys_str_mv AT paultwilliams quantiledependentexpressivityofserumuricacidconcentrations