Effect of Environmental Factors and Gender on the Heritability of Bone Mineral Density and Bone Size

Bone mineral density (BMD), a risk factor for osteoporosis, is believed to be under genetic control. The effect of environmental factors and gender on the heritability of BMD and bone size is ill‐defined. In this study, heritability estimates (h2) were determined in 3,320 southern Chinese subjects from 1,019 families using the variance components model. The h2 for age, weight and height‐adjusted BMD was 0.63–0.71 for females, and 0.74–0.79 for males; and for bone size, 0.44–0.64 for females and 0.32–0.86 for males. Adjustment for lifestyle factors including calcium and phytoestrogen intake, exercise, smoking and alcohol consumption altered the h2 differently in males and females. The proportion of variance in BMD and bone size explained by all covariates varied between skeletal sites, but was consistently greater in females than males. A significant gender difference was observed in the genetic variance of BMD and bone size at the hip but not the spine. In conclusion, a gender difference was observed in the degree of heritability of BMD and bone size at specific skeletal sites. Environmental influences contributed variably at different sites in the two sexes.

[1]  A. Uitterlinden,et al.  Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: the FAMOS study. , 2005, Human molecular genetics.

[2]  M. Alen,et al.  Association Between Exercise and Pubertal BMD Is Modulated by Estrogen Receptor α Genotype , 2004 .

[3]  L. Almasy,et al.  Assessment of sex‐specific genetic and environmental effects on bone mineral density , 2004, Genetic epidemiology.

[4]  R. Recker,et al.  Complex segregation analyses of bone mineral density in Chinese , 2004, Annals of human genetics.

[5]  D. Kiel,et al.  Genome screen for a combined bone phenotype using principal component analysis: the Framingham study. , 2004, Bone.

[6]  J. Long,et al.  High heritability of bone size at the hip and spine in Chinese , 2004, Journal of Human Genetics.

[7]  John Blangero,et al.  Quantitative Trait Loci on Chromosomes 2p, 4p, and 13q Influence Bone Mineral Density of the Forearm and Hip in Mexican Americans , 2003, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[8]  B. Mitchell,et al.  Genetic and environmental determinants of bone mineral density in Mexican Americans: results from the San Antonio Family Osteoporosis Study. , 2003, Bone.

[9]  D. Kiel,et al.  Age, gender, and body mass effects on quantitative trait loci for bone mineral density: the Framingham Study. , 2003, Bone.

[10]  Hong-Wen Deng,et al.  Searching for osteoporosis genes in the post-genome era: progress and challenges , 2003, Osteoporosis International.

[11]  E. Orwoll,et al.  Mapping Quantitative Trait Loci That Influence Femoral Cross‐sectional Area in Mice , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[12]  T. Spector,et al.  Gender Differences in the Genetic Factors Responsible for Variation in Bone Density and Ultrasound , 2002, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[13]  E. Orwoll,et al.  Gender Specificity in the Genetic Determinants of Peak Bone Mass , 2001, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[14]  J. Mei,et al.  High dietary phytoestrogen intake is associated with higher bone mineral density in postmenopausal but not premenopausal women. , 2001, The Journal of clinical endocrinology and metabolism.

[15]  I. Lambrinoudaki,et al.  Absence of high-risk “s” allele associated with osteoporosis at the intronic SP1 binding-site of collagen Iα1 gene in Southern Chinese , 2001, Journal of endocrinological investigation.

[16]  Susan R. Johnson,et al.  Osteoporosis prevention, diagnosis, and therapy. , 2001, JAMA.

[17]  L. Almasy,et al.  Multipoint quantitative-trait linkage analysis in general pedigrees. , 1998, American journal of human genetics.

[18]  K. Lau,et al.  Vitamin D receptor gene polymorphisms and peak bone mass in southern Chinese women. , 1998, Bone.

[19]  J. Ott,et al.  First-stage autosomal genome screen in extended pedigrees suggests genes predisposing to low bone mineral density on chromosomes 1p, 2p and 4q , 1998, European Journal of Human Genetics.

[20]  R. Rizzoli,et al.  Familial resemblance for bone mineral mass is expressed before puberty. , 1998, The Journal of clinical endocrinology and metabolism.

[21]  G. Siest,et al.  Segregation analysis and variance components analysis of bone mineral density in healthy families , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[22]  B. Dawson-Hughes,et al.  Vitamin D receptor alleles and rates of bone loss: Influences of years since menopause and calcium intake , 1995, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[23]  S. Cummings,et al.  Risk factors for hip fracture in white women. Study of Osteoporotic Fractures Research Group. , 1995, The New England journal of medicine.

[24]  A. Carothers Methodology for Genetic Studies of Twins and Families , 1994 .

[25]  C. Cooper,et al.  Hip fractures in the elderly: A world-wide projection , 1992, Osteoporosis International.

[26]  Michael C. Neale,et al.  Methodology for Genetic Studies of Twins and Families , 1992 .

[27]  C. Slemenda,et al.  Genetic determinants of bone mass in adult women: A reevaluation of the twin model and the potential importance of gene interaction on heritability estimates , 1991, Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research.

[28]  R. Tesar,et al.  Mother-daughter pairs: spinal and femoral bone densities and dietary intakes. , 1990, The American journal of clinical nutrition.

[29]  J. Hopper,et al.  Genetic determinants of bone mass in adults. A twin study. , 1987, The Journal of clinical investigation.

[30]  E. Tatum GENETIC DETERMINANTS , 1964 .

[31]  R. Recker,et al.  Evidence for a major gene underlying bone size variation in the Chinese , 2004, American journal of human biology : the official journal of the Human Biology Council.

[32]  S. Tam,et al.  Determinants of bone mineral density in Asian men , 2004 .

[33]  T. Spector,et al.  Comparison of genome screens for two independent cohorts provides replication of suggestive linkage of bone mineral density to 3p21 and 1p36. , 2003, American journal of human genetics.

[34]  T. Spector,et al.  Genetic Variation in Bone Mineral Density and Calcaneal Ultrasound: A Study of the Influence of Menopause Using Female Twins , 2001, Osteoporosis International.

[35]  K. Tsai,et al.  A Simple Tool to Identify Asian Women at Increased Risk of Osteoporosis , 2001, Osteoporosis International.

[36]  Harry K. Genant,et al.  Interim Report and Recommendations of the World Health Organization Task-Force for Osteoporosis , 1999, Osteoporosis International.

[37]  N. L. Johnson,et al.  Multivariate Analysis , 1958, Nature.