Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions

Abstract “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 inheri...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autor principal:	Paul T. Williams
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2020
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/555e4c01eac6454eb7af39bdb61283bc
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:555e4c01eac6454eb7af39bdb61283bc
record_format	dspace
spelling	oai:doaj.org-article:555e4c01eac6454eb7af39bdb61283bc2021-12-02T13:58:12ZQuantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions10.1038/s41598-020-79116-12045-2322https://doaj.org/article/555e4c01eac6454eb7af39bdb61283bc2020-12-01T00:00:00Zhttps://doi.org/10.1038/s41598-020-79116-1https://doaj.org/toc/2045-2322Abstract “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.Paul T. WilliamsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 10, Iss 1, Pp 1-13 (2020)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Paul T. Williams Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions
description	Abstract “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.
format	article
author	Paul T. Williams
author_facet	Paul T. Williams
author_sort	Paul T. Williams
title	Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions
title_short	Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions
title_full	Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions
title_fullStr	Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions
title_full_unstemmed	Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions
title_sort	quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions
publisher	Nature Portfolio
publishDate	2020
url	https://doaj.org/article/555e4c01eac6454eb7af39bdb61283bc
work_keys_str_mv	AT paultwilliams quantilespecificheritabilityofsiblingleptinconcentrationsanditsimplicationsforgeneenvironmentinteractions
_version_	1718392199153975296

Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions

Ejemplares similares