Tags

Type your tag names separated by a space and hit enter

Quantile-dependent heritability of computed tomography, dual-energy x-ray absorptiometry, anthropometric, and bioelectrical measures of adiposity.
Int J Obes (Lond). 2020 Oct; 44(10):2101-2112.IJ

Abstract

BACKGROUND/OBJECTIVES

Quantile-dependent expressivity occurs when a gene's phenotypic expression depends upon whether the trait (e.g., BMI) is high or low relative to its distribution. We have previously shown that the obesity effects of a genetic risk score (GRSBMI) increased significantly with increasing quantiles of BMI. However, BMI is an inexact adiposity measure and GRSBMI explains <3% of the BMI variance. The purpose of this paper is to test BMI for quantile-dependent expressivity using a more inclusive genetic measure (h2, heritability in the narrow sense), extend the result to other adiposity measures, and demonstrate its consistency with purported gene-environment interactions.

SUBJECTS/METHODS

Quantile-specific offspring-parent regression slopes (βOP) were obtained from quantile regression for height (ht) and computed tomography (CT), dual-energy x-ray absorptiometry (DXA), anthropometric, and bioelectrical impedance (BIA) adiposity measures. Heritability was estimated by 2βOP/(1 + rspouse) in 6227 offspring-parent pairs from the Framingham Heart Study, where rspouse is the spouse correlation.

RESULTS

Compared to h2 at the 10th percentile, genetic heritability was significantly greater at the 90th population percentile for BMI (3.14-fold greater, P < 10-15), waist girth/ht (3.27-fold, P < 10-15), hip girth/ht (3.12-fold, P = 6.3 × 10-14), waist-to-hip ratio (1.75-fold, P = 0.01), sagittal diameter/ht (3.89-fold, P = 3.7 × 10-7), DXA total fat/ht2 (3.62-fold, P = 0.0002), DXA leg fat/ht2 (3.29-fold, P = 2.0 × 10-11), DXA arm fat/ht2 (4.02-fold, P = 0.001), CT-visceral fat/ht2 (3.03-fold, P = 0.002), and CT-subcutaneous fat/ht2 (3.54-fold, P = 0.0004). External validity was suggested by the phenomenon's consistency with numerous published reports. Quantile-dependent expressivity potentially explains precision medicine markers for weight gain from overfeeding or antipsychotic medications, and the modifying effects of physical activity, sleep, diet, polycystic ovary syndrome, socioeconomic status, and depression on gene-BMI relationships.

CONCLUSIONS

Genetic heritabilities of anthropometric, CT, and DXA adiposity measures increase with increasing adiposity. Some gene-environment interactions may arise from analyzing subjects by characteristics that distinguish high vs. low adiposity rather than the effects of environmental stimuli on transcriptional and epigenetic processes.

Authors+Show Affiliations

Lawrence Berkeley National Laboratory, Molecular Biophysics & Integrated Bioimaging Division, 1 Cyclotron Rd, Berkeley, CA, 94720, USA. ptwilliams@lbl.gov.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32665611

Citation

Williams, Paul T.. "Quantile-dependent Heritability of Computed Tomography, Dual-energy X-ray Absorptiometry, Anthropometric, and Bioelectrical Measures of Adiposity." International Journal of Obesity (2005), vol. 44, no. 10, 2020, pp. 2101-2112.
Williams PT. Quantile-dependent heritability of computed tomography, dual-energy x-ray absorptiometry, anthropometric, and bioelectrical measures of adiposity. Int J Obes (Lond). 2020;44(10):2101-2112.
Williams, P. T. (2020). Quantile-dependent heritability of computed tomography, dual-energy x-ray absorptiometry, anthropometric, and bioelectrical measures of adiposity. International Journal of Obesity (2005), 44(10), 2101-2112. https://doi.org/10.1038/s41366-020-0636-1
Williams PT. Quantile-dependent Heritability of Computed Tomography, Dual-energy X-ray Absorptiometry, Anthropometric, and Bioelectrical Measures of Adiposity. Int J Obes (Lond). 2020;44(10):2101-2112. PubMed PMID: 32665611.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Quantile-dependent heritability of computed tomography, dual-energy x-ray absorptiometry, anthropometric, and bioelectrical measures of adiposity. A1 - Williams,Paul T, Y1 - 2020/07/14/ PY - 2019/11/20/received PY - 2020/07/03/accepted PY - 2020/06/07/revised PY - 2020/7/16/pubmed PY - 2020/7/16/medline PY - 2020/7/16/entrez SP - 2101 EP - 2112 JF - International journal of obesity (2005) JO - Int J Obes (Lond) VL - 44 IS - 10 N2 - BACKGROUND/OBJECTIVES: Quantile-dependent expressivity occurs when a gene's phenotypic expression depends upon whether the trait (e.g., BMI) is high or low relative to its distribution. We have previously shown that the obesity effects of a genetic risk score (GRSBMI) increased significantly with increasing quantiles of BMI. However, BMI is an inexact adiposity measure and GRSBMI explains <3% of the BMI variance. The purpose of this paper is to test BMI for quantile-dependent expressivity using a more inclusive genetic measure (h2, heritability in the narrow sense), extend the result to other adiposity measures, and demonstrate its consistency with purported gene-environment interactions. SUBJECTS/METHODS: Quantile-specific offspring-parent regression slopes (βOP) were obtained from quantile regression for height (ht) and computed tomography (CT), dual-energy x-ray absorptiometry (DXA), anthropometric, and bioelectrical impedance (BIA) adiposity measures. Heritability was estimated by 2βOP/(1 + rspouse) in 6227 offspring-parent pairs from the Framingham Heart Study, where rspouse is the spouse correlation. RESULTS: Compared to h2 at the 10th percentile, genetic heritability was significantly greater at the 90th population percentile for BMI (3.14-fold greater, P < 10-15), waist girth/ht (3.27-fold, P < 10-15), hip girth/ht (3.12-fold, P = 6.3 × 10-14), waist-to-hip ratio (1.75-fold, P = 0.01), sagittal diameter/ht (3.89-fold, P = 3.7 × 10-7), DXA total fat/ht2 (3.62-fold, P = 0.0002), DXA leg fat/ht2 (3.29-fold, P = 2.0 × 10-11), DXA arm fat/ht2 (4.02-fold, P = 0.001), CT-visceral fat/ht2 (3.03-fold, P = 0.002), and CT-subcutaneous fat/ht2 (3.54-fold, P = 0.0004). External validity was suggested by the phenomenon's consistency with numerous published reports. Quantile-dependent expressivity potentially explains precision medicine markers for weight gain from overfeeding or antipsychotic medications, and the modifying effects of physical activity, sleep, diet, polycystic ovary syndrome, socioeconomic status, and depression on gene-BMI relationships. CONCLUSIONS: Genetic heritabilities of anthropometric, CT, and DXA adiposity measures increase with increasing adiposity. Some gene-environment interactions may arise from analyzing subjects by characteristics that distinguish high vs. low adiposity rather than the effects of environmental stimuli on transcriptional and epigenetic processes. SN - 1476-5497 UR - https://www.unboundmedicine.com/medline/citation/32665611/Quantile_dependent_heritability_of_computed_tomography_dual_energy_x_ray_absorptiometry_anthropometric_and_bioelectrical_measures_of_adiposity_ L2 - http://dx.doi.org/10.1038/s41366-020-0636-1 DB - PRIME DP - Unbound Medicine ER -
Try the Free App:
Prime PubMed app for iOS iPhone iPad
Prime PubMed app for Android
Prime PubMed is provided
free to individuals by:
Unbound Medicine.