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Title: 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 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. Reportedmore » 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.« less

Authors:
 [1]
+ Show Author Affiliations
  1. Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Publication Date:
Research Org.:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Org.:
USDOE Office of Science (SC), Biological and Environmental Research (BER); National Institutes of Health (NIH)
OSTI Identifier:
1827662
Grant/Contract Number:  
AC02-05CH11231; N01-HC-25195; HHSN268201500001I
Resource Type:
Accepted Manuscript
Journal Name:
Scientific Reports
Additional Journal Information:
Journal Volume: 10; Journal Issue: 1; Journal ID: ISSN 2045-2322
Publisher:
Nature Publishing Group
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES

Citation Formats

Williams, Paul T. Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions. United States: N. p., 2020. Web. doi:10.1038/s41598-020-79116-1.
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Williams, Paul T. Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions. United States. https://doi.org/10.1038/s41598-020-79116-1
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Williams, Paul T. Thu . "Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions". United States. https://doi.org/10.1038/s41598-020-79116-1. https://www.osti.gov/servlets/purl/1827662.
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@article{osti_1827662,
title = {Quantile-specific heritability of sibling leptin concentrations and its implications for gene-environment interactions},
author = {Williams, Paul T.},
abstractNote = {“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.},
doi = {10.1038/s41598-020-79116-1},
journal = {Scientific Reports},
number = 1,
volume = 10,
place = {United States},
year = {Thu Dec 17 00:00:00 EST 2020},
month = {Thu Dec 17 00:00:00 EST 2020}
}
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Works referenced in this record:

Heritability of free and receptor-bound leptin in normal twins
journal, May 2005

  • Jordan, Jens; Brabant, Georg; Brinsuk, Marina
  • American Journal of Physiology-Regulatory, Integrative and Comparative Physiology, Vol. 288, Issue 5
  • DOI: 10.1152/ajpregu.00446.2004

Body Fat Mass and Macronutrient Intake in Relation to Circulating Soluble Leptin Receptor, Free Leptin Index, Adiponectin, and Resistin Concentrations in Healthy Humans
journal, April 2003

  • Yannakoulia, Mary; Yiannakouris, Nikos; Blüher, Susann
  • The Journal of Clinical Endocrinology & Metabolism, Vol. 88, Issue 4
  • DOI: 10.1210/jc.2002-021604

Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels
journal, February 2016

  • Kilpeläinen, Tuomas O.; Carli, Jayne F. Martin; Skowronski, Alicja A.
  • Nature Communications, Vol. 7, Issue 1
  • DOI: 10.1038/ncomms10494

Familial Resemblance for Plasma Leptin: Sample Homogeneity across Adiposity and Ethnic Groups
journal, May 2002

  • Rice, Treva; Chagnon, Yvon C.; Borecki, Ingrid B.
  • Obesity Research, Vol. 10, Issue 5
  • DOI: 10.1038/oby.2002.49

Cardiovascular Disease Among Transgender Adults Receiving Hormone Therapy: A Narrative Review
journal, July 2017

  • Streed, Carl G.; Harfouch, Omar; Marvel, Francoise
  • Annals of Internal Medicine, Vol. 167, Issue 4
  • DOI: 10.7326/M17-0577

Heritability of obesity-related traits among Nigerians, Jamaicans and US black people
journal, July 2001

  • Luke, A.; Guo, X.; Adeyemo, Aa
  • International Journal of Obesity, Vol. 25, Issue 7
  • DOI: 10.1038/sj.ijo.0801650

Potential role of leptin in angiogenesis: leptin induces endothelial cell proliferation and expression of matrix metalloproteinases in vivo and in vitro
journal, June 2001

  • Park, Hyun-Young; Kwon, Hyuck Moon; Lim, Hyun Joung
  • Experimental & Molecular Medicine, Vol. 33, Issue 2
  • DOI: 10.1038/emm.2001.17

Plasma Leptin Levels: Interaction of Obesity With a Common Variant of Insulin Receptor Substrate-1
journal, November 1998

  • Krempler, Franz; Hell, Emanuel; Winkler, Carmen
  • Arteriosclerosis, Thrombosis, and Vascular Biology, Vol. 18, Issue 11
  • DOI: 10.1161/01.ATV.18.11.1686

Sibling and parent--offspring correlation estimation with variable family size.
journal, May 1981

  • Karlin, S.; Cameron, E. C.; Williams, P. T.
  • Proceedings of the National Academy of Sciences, Vol. 78, Issue 5
  • DOI: 10.1073/pnas.78.5.2664

Polymorphism in Leptin and Leptin Receptor Genes May Modify Leptin Levels and Represent Risk Factors for Multiple Sclerosis
journal, April 2016

Association of leptin levels with obesity and blood pressure: possible common genetic variation
journal, October 2004

  • Livshits, G.; Pantsulaia, I.; Gerber, L. M.
  • International Journal of Obesity, Vol. 29, Issue 1
  • DOI: 10.1038/sj.ijo.0802826

Leptin: physiology and pathophysiology: Leptin
journal, October 1998

Quantitative trait loci on chromosomes 3 and 17 influence phenotypes of the metabolic syndrome
journal, December 2000

  • Kissebah, A. H.; Sonnenberg, G. E.; Myklebust, J.
  • Proceedings of the National Academy of Sciences, Vol. 97, Issue 26
  • DOI: 10.1073/pnas.97.26.14478

Relationship between Adipocyte Size and Adipokine Expression and Secretion
journal, March 2007

  • Skurk, Thomas; Alberti-Huber, Catherine; Herder, Christian
  • The Journal of Clinical Endocrinology & Metabolism, Vol. 92, Issue 3
  • DOI: 10.1210/jc.2006-1055

Genotype by smoking interaction for leptin levels in the San Antonio family heart study
journal, January 2002

  • Martin, Lisa J.; Cole, Shelley A.; Hixson, James E.
  • Genetic Epidemiology, Vol. 22, Issue 2
  • DOI: 10.1002/gepi.0135

An autosomal genomic scan for loci linked to plasma leptin concentration in Pima Indians
journal, May 2000

  • Walder, K.; Hanson, Rl; Kobes, S.
  • International Journal of Obesity, Vol. 24, Issue 5
  • DOI: 10.1038/sj.ijo.0801197

A Twin Study for Serum Leptin, Soluble Leptin Receptor, and Free Insulin-Like Growth Factor-I in Pubertal Females
journal, June 2005

  • Li, Hong-juan; Ji, Cheng-ye; Wang, Wei
  • The Journal of Clinical Endocrinology & Metabolism, Vol. 90, Issue 6
  • DOI: 10.1210/jc.2004-2079

The Third Generation Cohort of the National Heart, Lung, and Blood Institute's Framingham Heart Study: Design, Recruitment, and Initial Examination
journal, April 2007

  • Splansky, G. L.; Corey, D.; Yang, Q.
  • American Journal of Epidemiology, Vol. 165, Issue 11
  • DOI: 10.1093/aje/kwm021

Quantile-specific heritability of high-density lipoproteins with implications for precision medicine
journal, July 2020

Quantile-Dependent Expressivity and Gene-Lifestyle Interactions Involving High-Density Lipoprotein Cholesterol
journal, December 2020

Generation of Human Soluble Leptin Receptor by Proteolytic Cleavage of Membrane-Anchored Receptors
journal, October 2001

Correlation between serum leptin and its gene expression to the anthropometric measures in overweight and obese children
journal, January 2018

  • Eldosouky, Maha K.; Abdu Allah, Azza M.; AbdElmoneim, Abeer
  • Cellular and Molecular Biology, Vol. 64, Issue 1
  • DOI: 10.14715/cmb/2018.64.1.15

Quantile-Specific Heritability of Intakes of Alcohol but not Other Macronutrients
journal, July 2020

Sex differences in body fat distribution are related to sex differences in serum leptin and adiponectin
journal, September 2018

Quantile-dependent expressivity of postprandial lipemia
journal, February 2020

Serum Leptin Levels, Leptin Receptor Gene (LEPR) Polymorphism, and the Risk of Systemic Lupus Erythematosus in Kashmiri Population
journal, November 2014

Generation of Soluble Leptin Receptor by Ectodomain Shedding of Membrane-spanning Receptors in Vitro and in Vivo
journal, November 2002

  • Ge, Hongfei; Huang, Lu; Pourbahrami, Tiffany
  • Journal of Biological Chemistry, Vol. 277, Issue 48
  • DOI: 10.1074/jbc.M205825200

Leptin's Sexual Dimorphism Results from Genotype by Sex Interactions Mediated by Testosterone
journal, January 2002

  • Martin, Lisa J.; Mahaney, Michael C.; Almasy, Laura
  • Obesity Research, Vol. 10, Issue 1
  • DOI: 10.1038/oby.2002.3

Diabetes in the Old Order Amish: characterization and heritability analysis of the Amish Family Diabetes Study
journal, May 2000

Mechanisms behind gender differences in circulating leptin levels
journal, April 2000

Heritability of plasma leptin in a population sample of African-American families
journal, January 1997

Soluble Leptin Receptor Represents the Main Leptin Binding Activity in Human Blood
journal, May 2001

  • Lammert, A.; Kiess, W.; Bottner, A.
  • Biochemical and Biophysical Research Communications, Vol. 283, Issue 4
  • DOI: 10.1006/bbrc.2001.4885

A major quantitative trait locus determining serum leptin levels and fat mass is located on human chromosome 2
journal, March 1997

  • Comuzzie, Anthony G.; Hixson, James E.; Almasy, Laura
  • Nature Genetics, Vol. 15, Issue 3
  • DOI: 10.1038/ng0397-273

Evidence of free and bound leptin in human circulation. Studies in lean and obese subjects and during short-term fasting.
journal, September 1996

  • Sinha, M. K.; Opentanova, I.; Ohannesian, J. P.
  • Journal of Clinical Investigation, Vol. 98, Issue 6
  • DOI: 10.1172/JCI118913

Common Genetic Components of Obesity Traits and Serum Leptin
journal, December 2008

  • Hasselbalch, Ann L.; Benyamin, Beben; Visscher, Peter M.
  • Obesity, Vol. 16, Issue 12
  • DOI: 10.1038/oby.2008.440

Genome-wide association study identifies polymorphisms in LEPR as determinants of plasma soluble leptin receptor levels
journal, February 2010

  • Sun, Qi; Cornelis, Marilyn C.; Kraft, Peter
  • Human Molecular Genetics, Vol. 19, Issue 9
  • DOI: 10.1093/hmg/ddq056

Quantile Regression
journal, November 2001

  • Koenker, Roger; Hallock, Kevin F.
  • Journal of Economic Perspectives, Vol. 15, Issue 4
  • DOI: 10.1257/jep.15.4.143

Heritability of leptin levels and the shared genetic effects on body mass index and leptin in adult Finnish twins
journal, January 2001

  • Kaprio, J.; Eriksson, J.; Lehtovirta, M.
  • International Journal of Obesity, Vol. 25, Issue 1
  • DOI: 10.1038/sj.ijo.0801526

Lack of heritability of circulating leptin concentration in humans after adjustment for body size and adiposity using a physiological approach
journal, November 2001

  • Jenkins, Ab; Samaras, K.; Gordon, Ma
  • International Journal of Obesity, Vol. 25, Issue 11
  • DOI: 10.1038/sj.ijo.0801802

Heritability of plasma leptin levels: a twin study
journal, January 1999

Quantile-Specific Penetrance of Genes Affecting Lipoproteins, Adiposity and Height
journal, January 2012

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