Abstract
Summary
Bone mineral density (BMD), a representative marker of osteoporosis risk, is found to be highly heritable in this Korean study, which is very consistent with the findings in Western populations. This finding strongly supports that genetic factors are significant determinants of osteoporosis risk along with individual biological and behavioral factors.
Introduction
Although genetic factors are known to contribute significantly to variations in BMD in Western populations, such an association has not been fully evaluated in an Asian population. This study was conducted to determine the role of genetic factors on BMD in Korean population.
Methods
The study participants were 2,728 men and women consisting of 497 monozygotic (MZ) twin pairs, 119 dizygotic (DZ) twin pairs, and 1,496 first-degree relatives from the Healthy Twin Study. BMD was measured using dual-energy X-ray absorptiometry. Quantitative genetic analysis based on a variance decomposition model was performed.
Results
Age and the measured covariates accounted for 17~61% of the variation in BMD, depending on the sites of measurement. After accounting for the covariate effects, the heritability of BMD at the whole body, thoracic and lumbar spine, whole ribs, whole pelvis, whole arms, and whole legs were 0.76, 0.72, 0.73, 0.71, 0.51, and 0.75, respectively. The pair-wise correlation of BMD was the highest within MZ twin pairs, followed by DZ twin pairs, sibling pairs, and parents–child pairs. Cross-trait correlation analysis revealed a positive genetic correlation between BMDs at different sites, ranging from 0.80 (arm and leg BMD) to 0.50 (pelvis and arm BMD).
Conclusions
The high heritability of BMD in this Korean population similar to those found in Western populations and the significant common genetic basis between BMDs at different sites strongly supports a significant role of genetic determinants on the risk of osteoporosis.
Similar content being viewed by others
References
Dennison E, Cole Z, Cooper C (2005) Diagnosis and epidemiology of osteoporosis. Curr Opin Rheumatol 17:456–461
Cummings SR, Melton LJ (2002) Epidemiology and outcomes of osteoporotic fractures. Lancet 359:1761–1767
Genant HK, Cooper C, Poor G et al (1999) Interim report and recommendations of the World Health Organization Task-Force for Osteoporosis. Osteoporos Int 10:259–264
Tse KY, Macias BR, Meyer RS et al (2009) Heritability of bone density: regional and gender differences in monozygotic twins. J Orthop Res 27:150–154
Harris M, Nguyen TV, Howard GM et al (1998) Genetic and environmental correlations between bone formation and bone mineral density: a twin study. Bone 22:141–145
Nguyen TV, Howard GM, Kelly PJ et al (1998) Bone mass, lean mass, and fat mass: same genes or same environments? Am J Epidemiol 147:3–16
Bogl LH, Latvala A, Kaprio J et al (2010) An investigation into the relationship between soft tissue body composition and bone mineral density in a young adult twin sample. J Bone Miner Res 26(1):79–87
Arden NK, Baker J, Hogg C et al (1996) The heritability of bone mineral density, ultrasound of the calcaneus and hip axis length: a study of postmenopausal twins. J Bone Miner Res 11:530–534
Videman T, Levalahti E, Battie MC et al (2007) Heritability of BMD of femoral neck and lumbar spine: a multivariate twin study of Finnish men. J Bone Miner Res 22:1455–1462
Sigurdsson G, Halldorsson BV, Styrkarsdottir U et al (2008) Impact of genetics on low bone mass in adults. J Bone Miner Res 23:1584–1590
Deng HW, Chen WM, Conway T et al (2000) Determination of bone mineral density of the hip and spine in human pedigrees by genetic and life-style factors. Genet Epidemiol 19:160–177
Brown LB, Streeten EA, Shuldiner AR et al (2004) Assessment of sex-specific genetic and environmental effects on bone mineral density. Genet Epidemiol 27:153–161
Mitchell BD, Kammerer CM, Schneider JL et al (2003) Genetic and environmental determinants of bone mineral density in Mexican Americans: results from the San Antonio Family Osteoporosis Study. Bone 33:839–846
Lee M, Czerwinski SA, Choh AC et al (2006) Unique and common genetic effects between bone mineral density and calcaneal quantitative ultrasound measures: the Fels Longitudinal Study. Osteoporos Int 17:865–871
Duncan EL, Cardon LR, Sinsheimer JS et al (2003) Site and gender specificity of inheritance of bone mineral density. J Bone Miner Res 18:1531–1538
Ng MY, Sham PC, Paterson AD et al (2006) Effect of environmental factors and gender on the heritability of bone mineral density and bone size. Ann Hum Genet 70:428–438
Deng FY, Lei SF, Li MX et al (2006) Genetic determination and correlation of body mass index and bone mineral density at the spine and hip in Chinese Han ethnicity. Osteoporos Int 17:119–124
Liu PY, Qin YJ, Zhou Q et al (2004) Complex segregation analyses of bone mineral density in Chinese. Ann Hum Genet 68:154–164
Pollitzer WS, Anderson JJ (1989) Ethnic and genetic differences in bone mass: a review with a hereditary vs environmental perspective. Am J Clin Nutr 50:1244–1259
Barrett-Connor E, Siris ES, Wehren LE et al (2005) Osteoporosis and fracture risk in women of different ethnic groups. J Bone Miner Res 20:185–194
Sung J, Cho SI, Lee K et al (2006) Healthy Twin: a twin-family study of Korea—protocols and current status. Twin Res Hum Genet 9:844–848
Song YM, Lee D, Lee MK et al (2010) Validity of the zygosity questionnaire and characteristics of zygosity-misdiagnosed twin pairs in the Healthy Twin Study of Korea. Twin Res Hum Genet 13:223–230
Ahn Y, Kwon E, Shim JE et al (2007) Validation and reproducibility of food frequency questionnaire for Korean genome epidemiologic study. Eur J Clin Nutr 61:1435–1441
Ralston SH, Uitterlinden AG (2010) Genetics of osteoporosis. Endocr Rev 31:629–662
Keen RW, Hart DJ, Arden NK et al (1999) Family history of appendicular fracture and risk of osteoporosis: a population-based study. Osteoporos Int 10:161–166
Jouanny P, Guillemin F, Kuntz C et al (1995) Environmental and genetic factors affecting bone mass. Similarity of bone density among members of healthy families. Arthritis Rheum 38:61–67
Yang TL, Zhao LJ, Liu YJ et al (2006) Genetic and environmental correlations of bone mineral density at different skeletal sites in females and males. Calcif Tissue Int 78:212–217
Mughal MZ, Eelloo J, Roberts SA et al (2010) Body composition and bone status of children born to mothers with type 1 diabetes mellitus. Arch Dis Child 95:281–285
Tobias JH, Steer CD, Emmett PM et al (2005) Bone mass in childhood is related to maternal diet in pregnancy. Osteoporos Int 16:1731–1741
Livshits G, Deng HW, Nguyen TV et al (2004) Genetics of bone mineral density: evidence for a major pleiotropic effect from an intercontinental study. J Bone Miner Res 19:914–923
Wang L, Liu YJ, Xiao P et al (2007) Chromosome 2q32 may harbor a QTL affecting BMD variation at different skeletal sites. J Bone Miner Res 22:1672–1678
Hsu YH, Xu X, Terwedow HA et al (2007) Large-scale genome-wide linkage analysis for loci linked to BMD at different skeletal sites in extreme selected sibships. J Bone Miner Res 22:184–194
Karasik D, Hsu YH, Zhou Y et al (2010) Genome-wide pleiotropy of osteoporosis-related phenotypes: the Framingham Study. J Bone Miner Res 25:1555–1563
Naganathan V, Macgregor A, Snieder H et al (2002) Gender differences in the genetic factors responsible for variation in bone density and ultrasound. J Bone Miner Res 17:725–733
Slemenda CW, Christian JC, Williams CJ et al (1991) Genetic determinants of bone mass in adult women: a reevaluation of the twin model and the potential importance of gene interaction on heritability estimates. J Bone Miner Res 6:561–567
Acknowledgment
This study was supported by the National Genome Research Institute, Korea, National Institute of Health research contract (budgets 2005-347-2400-2440-215, 2006-347-2400-2440-215, 2007-347-2400-2440-215, 2008-E00255-00, and 2009-E00500-00), Korean Ministry of Education, Science and Technology, (Grant Number M10305030005), and the Samsung Biomedical Research Institute(#SBRI C- A9-218-1). The views expressed in this paper are those of the authors and not necessarily any funding body.
Conflicts of interest
None.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Park, JH., Song, YM., Sung, J. et al. Genetic influence on bone mineral density in Korean twins and families: the healthy twin study. Osteoporos Int 23, 1343–1349 (2012). https://doi.org/10.1007/s00198-011-1685-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00198-011-1685-z