Contribution of body composition components and soft‐tissue biochemical factors to genetic variation of body mass index (BMI) in an ethnically homogeneous population

Dosaev, Tasbulat; Prakash, Jai; Livshits, Gregory

doi:10.1002/ajhb.22583

Cited by 8 publications

(9 citation statements)

References 47 publications

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“…Women have higher adiponectin concentrations due at least in part to the adiponectionlowering effects of testosterone (Berra et al, 2006). Whereas sex-differences in adiponectin concentrations are consistently reported (Liu et al, 2008;Hicks et al, 2007;Comuzzie et al, 2001;Vaughan et al, 2015;Chuang et al, 2004;Dosaev, Prakash & Livshits, 2014;Henneman et al, 2010;Guo et al, 2006;Ling, Waterworth et al, 2009;Vasseur et al, 2002;Cesari et al, 2007), sex-differences in their heritabilities are not. This we attribute to their reliance on statistical procedures that require normally distributed data and logarithmic or other data transformations.…”

Section: Discussionmentioning

confidence: 99%

Quantile-dependent expressivity of plasma adiponectin concentrations may explain its sex-specific heritability, gene-environment interactions, and genotype-specific response to postprandial lipemia

Williams

2020

PeerJ

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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 (βOP,h2 = 2βOP/(1 + rspouse)) and full-sib regression slopes (βFS, h2 = {(1 + 8rspouseβFS)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 βOP (Ptrend = 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 βFS (Ptrend = 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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Section: Discussionmentioning

confidence: 99%

Quantile-dependent expressivity of plasma adiponectin concentrations may explain its sex-specific heritability, gene-environment interactions, and genotype-specific response to postprandial lipemia

Williams

2020

PeerJ

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“…A potential limitation of this strategy of adjusting for fat mass is that the ability to identify genetic signals with an impact on both lean mass and fat mass will be reduced. Some studies suggested lean mass and fat mass have a substantial genetic correlation (5,6).…”

Section: Introductionmentioning

confidence: 99%

Disentangling the genetics of lean mass

Karasik

Zillikens

Hsu

et al. 2019

The American Journal of Clinical Nutrition

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Background: Lean body mass (LM) plays an important role in mobility and metabolic function. We previously identified five loci associated with LM adjusted for fat mass in kilograms. Such an adjustment may reduce the power to identify genetic signals having an association with both lean mass and fat mass. Objectives: To determine the impact of different fat mass adjustments on genetic architecture of LM and identify additional LM loci. Methods: We performed genome-wide association analyses for whole-body LM (20 cohorts of European ancestry with n = 38,292) measured using dual-energy X-ray absorptiometry) or bioelectrical impedance analysis, adjusted for sex, age, age 2 , and height with or without fat mass adjustments (Model 1 no fat adjustment; Model 2 adjustment for fat mass as a percentage of body mass; Model 3 adjustment for fat mass in kilograms). Results: Seven single-nucleotide polymorphisms (SNPs) in separate loci, including one novel LM locus (TNRC6B), were successfully replicated in an additional 47,227 individuals from 29 cohorts. Based Conclusions: In conclusion, we identified one novel LM locus (TNRC6B). Our results suggest that a genetically determined increase in lean mass might exert either harmful or protective effects on metabolic traits, depending on its relation to fat mass.

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“…Similar results have been obtained for leptin [ 17 – 19 ]. To better elucidate the role of adipocytokines in the development of insulin resistance and diabetes, it is thus critical to investigate the associations of adiponectin and leptin with insulin resistance because most previous studies have focused on evaluating the associations of these adipocytokines with obesity and diabetes [ 14 , 20 , 21 ]. Therefore, the present study sought to examine the associations of serum adiponectin and leptin with β-cell function and insulin resistance among a large sample of the rural Chinese population whose prevalence rates of overweight and obesity are substantially lower than those of Western populations largely due to differences in dietary and lifestyle factors [ 22 ].…”

Section: Introductionmentioning

confidence: 99%

Associations between serum adipocytokines and glycemic tolerance biomarkers in a rural Chinese population

Zhao

Jin

et al. 2017

PLoS ONE

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Although experimental studies have shown that adiponectin and leptin modulate glucose tolerance and insulin resistance, it remains unclear whether these adipocytokines exert similar effects in general human populations. We evaluated the associations of serum adiponectin and leptin with β-cell function and insulin resistance in a population with low obesity prevalence. A cross-sectional study of 783 rural residents, aged 25–74 years, recruited in Ningxia, China was conducted during 2008–2012. β-cell function and insulin resistance were estimated using the Homeostasis Model Assessment. Serum adiponectin and leptin were measured with ELISA. Serum adiponectin concentrations (mean ± SD) were highest in subjects with normal glucose tolerance (36.65 ± 61.13 μg/ml), intermediate in those with impaired fasting glucose (25.92 ± 34.48 μg/ml), and lowest in those with diabetes (15.08 ± 12.14 μg/ml) (p = 0.001). A similar pattern of differences was found for β-cell function, whereas opposite results were observed for insulin resistance and blood glucose. After adjustment for confounders including metabolic syndrome components, serum adiponectin (μg/ml) was inversely associated with β-cell function (%β) [β (95% CI): -7.57 (-12.33, -2.81)] and insulin resistance (100/%S) [β (95% CI): -0.21 (-0.33, -0.09)]. A significant inverse association also existed between serum leptin and β-cell function, but serum leptin was not significantly associated with insulin resistance. The present study suggests that adiponectin and leptin play a role in the development of insulin resistance and diabetes independent of metabolic syndrome.

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Contribution of body composition components and soft‐tissue biochemical factors to genetic variation of body mass index (BMI) in an ethnically homogeneous population

Abstract: This study clearly suggests that FM and FFM contributed almost equally to BMI variation, and provides evidence that this contribution is caused by common genetic as well as shared environmental and metabolic factors.

Cited by 8 publications

References 47 publications

Quantile-dependent expressivity of plasma adiponectin concentrations may explain its sex-specific heritability, gene-environment interactions, and genotype-specific response to postprandial lipemia

Quantile-dependent expressivity of plasma adiponectin concentrations may explain its sex-specific heritability, gene-environment interactions, and genotype-specific response to postprandial lipemia

Disentangling the genetics of lean mass

Associations between serum adipocytokines and glycemic tolerance biomarkers in a rural Chinese population

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