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Heritability of Bone Mineral Density in a Multivariate Family-Based Study

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Abstract

There is evidence for a genetic contribution to bone mineral density (BMD×). Different loci affecting BMD have been identified by diverse linkage and genome-wide association studies. We studied the heritability of and the correlations among six densitometric phenotypes and four bone mass/fracture phenotypes. For this purpose, we used a family-based study of the genetics of osteoporosis, the Genetic Analysis of Osteoporosis Project. The primary aim of our study was to examine the roles of genetic and environmental factors in determining osteoporosis-related phenotypes. The project consisted of 11 extended families from Spain. All of them were selected through a proband with osteoporosis. BMD was measured using dual-energy X-ray absorptiometry. The proportion of variance of BMD attributable to significant covariates ranged from 25 % (for femoral neck BMD) to 48 % (for whole-body total BMD). The vast majority of the densitometric phenotypes had highly significant heritability, ranging from 0.252 (whole-body total BMD) to 0.537 (trochanteric BMD) after correcting for covariate effects. All of the densitometric phenotypes showed high and significant genetic correlations (from −0.772 to −1.000) with a low bone mass/osteopenia condition (Affected 3). Our findings provide additional evidence on the heritability of BMD and a strong genetic correlation between BMD and bone mass/fracture phenotypes in a Spanish population. Our results emphasize the importance of detecting genetic risk factors and the benefit of early diagnosis and especially therapeutic and preventive strategies.

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Acknowledgments

The authors gratefully acknowledge all of the families who participated in the GAO Project. Without them, this work could never have been accomplished. The project was partially supported by the National Fund of Sanitary Investigations (FIS PI 11/01175). G. Athanasiadis was supported by the Subprograma Nacional de Contratación e Incorporación de Investigadores Juan de la Cierva (MICINN). We thank W. H. Stone for his helpful advice and constructive discussions.

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Authors and Affiliations

  1. Department of Internal Medicine, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain

    Nerea Hernandez-de Sosa, Jorge Malouf, Ana Laiz, Ana Marin, Silvia Herrera, Jordi Farrerons & Jordi Casademont

  2. Department of Genomics of Complex Diseases, Research Institute, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain

    Georgios Athanasiadis & Jose Manuel Soria

  3. Unit of Internal Medicine, Hospital de la Santa Creu i Sant Pau, c/ Sant Antoni Maria Claret, 167, 08025, Barcelona, Spain

    Nerea Hernandez-de Sosa

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  1. Nerea Hernandez-de Sosa
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Correspondence to Nerea Hernandez-de Sosa.

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Appendix

Appendix

Definitions

  • Level of sun exposure was defined as the weekly number of hours of exposure between 11:00 am and 2:00 pm.

  • Dietary calcium intake was defined as the number of glasses of milk or portions of yogurt or cheese that were consumed weekly.

  • Physical activity was quantified through the International Physical Activity Questionnaire [44]. Activity was classified as high, moderate, or low on the categorical score.

  • Smoking habit was evaluated as either ongoing or finished. Consumption was calculated as packs per year, and when finished, nonsmoking time was measured in years.

  • Alcohol habit was defined as nonconsumption, low consumption (less than 30 g/day or 3 units), moderate consumption (30–40 g/day or 3–4 units), and high consumption (more than 40 g/day or 4 units).

  • Coffee intake was estimated as 0, 1–2, 2–4, or >4 cups of coffee per day. Weight was measured in kilograms (within 0.1 kg of accuracy), height in centimeters (within 0.5 cm of accuracy), and BMI (kg/m2).

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Sosa, N.Hd., Athanasiadis, G., Malouf, J. et al. Heritability of Bone Mineral Density in a Multivariate Family-Based Study. Calcif Tissue Int 94, 590–596 (2014). https://doi.org/10.1007/s00223-014-9852-9

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  • DOI: https://doi.org/10.1007/s00223-014-9852-9

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