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Quantile-Specific Heritability may Account for Gene-Environment Interactions Involving Coffee Consumption.

ABSTRACT: Estimated heritability of coffee intake ranges from 0.36 to 0.58, however, these point estimates assume that inherited effects are the same throughout the distribution of coffee intake, i.e., whether consumption is high or low relative to intake in the population. Quantile regression of 4788 child-parent pairs and 2380 siblings showed that offspring-parent and sibling concordance became progressively greater with increasing quantiles of coffee intake. Each cup/day increase in the parents' coffee intake was associated with an offspring increase of 0.020?±?0.013 cup/day at the 10th percentile of the offsprings' coffee intake (slope?±?SE, NS), 0.137?±?0.034 cup/day at their 25th percentile (P?=?5.2?×?10-5), 0.159?±?0.029 cup/day at the 50th percentile (P?=?5.8?×?10-8), 0.233?±?0.049 cup/day at the 75th percentile (P?=?1.8?×?10-6), and 0.284?±?0.054 cup/day at the 90th percentile (P?=?1.2?×?10-7). This quantile-specific heritability suggests that factors that distinguish heavier vs. lighter drinkers (smoking, male sex) will likely manifest differences in estimated heritability, as reported.

SUBMITTER: Williams PT

PROVIDER: S-EPMC7531626 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature

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Quantile-Specific Heritability may Account for Gene-Environment Interactions Involving Coffee Consumption.

Williams Paul T PT

Behavior genetics 20200103 2

Estimated heritability of coffee intake ranges from 0.36 to 0.58, however, these point estimates assume that inherited effects are the same throughout the distribution of coffee intake, i.e., whether consumption is high or low relative to intake in the population. Quantile regression of 4788 child-parent pairs and 2380 siblings showed that offspring-parent and sibling concordance became progressively greater with increasing quantiles of coffee intake. Each cup/day increase in the parents' coffee ...[more]

PMID: 31900678

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Project description:"Quantile-dependent expressivity" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g., leptin) is high or low relative to its distribution. Leptin concentrations are strongly related to adiposity, whose heritability is quantile dependent. Whether inheritance of leptin concentrations is quantile dependent, and whether this explains the greater heritability in women than men in accordance with their greater adiposity, and explains other gene-environment interactions, remains to be determined. Therefore, leptin and leptin receptor concentrations from 3068 siblings in 1133 sibships from the Framingham Heart Study Third Generation Cohort were analyzed. Free leptin index (FLI) was calculated as the ratio of leptin to soluble leptin receptor concentrations. Full-sib (βFS) regression slopes were robustly estimated by quantile regression with nonparametric significance assigned from 1000 bootstrap samples. The analyses showed βFS increased significantly with increasing percentiles of the offspring's age- and sex-adjusted leptin distribution (Plinear = 0.0001), which was accelerated at the higher concentrations (Pquadratic = 0.0003). βFS at the 90th percentile (0.418 ± 0.066) was 4.7-fold greater than at the 10th percentile (0.089 ± 0.032, Pdifference = 3.6 × 10-6). Consistent with quantile-dependent expressivity, the βFS was greater in female sibs, which was attributable to their higher leptin concentrations. Reported gene-environment interactions involving adiposity and LEP, LEPR, MnSOD, PPARγ, PPARγ2, and IRS-1 polymorphisms were consistent with quantile-dependent expressivity of leptin concentrations. βFS for leptin receptor concentrations and free leptin index also increased significantly with increasing percentiles of their distributions (Plinear = 0.04 and Plinear = 8.5 × 10-6, respectively). In conclusion, inherited genetic and shared environmental effects on leptin concentrations were quantile dependent, which likely explains male-female differences in heritability and some gene-environment interactions.

Project description:Background:"Quantile-dependent expressivity" occurs when the effect size of a genetic variant depends upon whether the phenotype (e.g. adiponectin) is high or low relative to its distribution. We have previously shown that the heritability (h2 ) of adiposity, lipoproteins, postprandial lipemia, pulmonary function, and coffee and alcohol consumption are quantile-specific. Whether adiponectin heritability is quantile specific remains to be determined. Methods:Plasma adiponectin concentrations from 4,182 offspring-parent pairs and 1,662 sibships from the Framingham Heart Study were analyzed. Quantile-specific heritability from offspring-parent (? OP,h2 = 2? OP/(1 + rspouse)) and full-sib regression slopes (? FS, h2 = {(1 + 8rspouse ? FS)0.05-1}/(2rspouse)) were robustly estimated by quantile regression with nonparametric significance assigned from 1,000 bootstrap samples. Results:Quantile-specific h2 (± SE) increased with increasing percentiles of the offspring's age- and sex-adjusted adiponectin distribution when estimated from ? OP (P trend = 2.2 × 10-6): 0.30 ± 0.03 at the 10th, 0.33 ± 0.04 at the 25th, 0.43 ± 0.04 at the 50th, 0.55 ± 0.05 at the 75th, and 0.57 ± 0.08 at the 90th percentile, and when estimated from ? FS (P trend = 7.6 × 10-7): 0.42 ± 0.03 at the 10th, 0.44 ± 0.04 at the 25th, 0.56 ± 0.05 at the 50th, 0.73 ± 0.08 at the 75th, and 0.79 ± 0.11 at the 90th percentile. Consistent with quantile-dependent expressivity, adiponectin's: (1) heritability was greater in women in accordance with their higher adiponection concentrations; (2) relationships to ADIPOQ polymorphisms were modified by adiposity in accordance with its adiponectin-lowering effect; (3) response to rosiglitazone was predicted by the 45T> G ADIPOQ polymorphism; (4) difference by ADIPOQ haplotypes increased linearly with increasing postprandial adiponectin concentrations. Conclusion:Adiponectin heritability is quantile dependent, which may explain sex-specific heritability, gene-environment and gene-drug interactions, and postprandial response by haplotypes.

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Dataset Information

Quantile-Specific Heritability may Account for Gene-Environment Interactions Involving Coffee Consumption.

Publications

Quantile-Specific Heritability may Account for Gene-Environment Interactions Involving Coffee Consumption.

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