Genetic Studies Of Bone Mineral Density And Stature And Correlation Analysis Between Them

Osteoporosis is a widely and seriously influenced complex disorder related to bone tissue. Low bone mineral density (BMD) is recognized as a major risk factor of osteoporosis. Extensive data have established that BMD variation is under strong genetic control. Adult height (stature), as an important parameter of human physical development, has been studied in many populations. The heritability of height is generally above 50% and is among the highest of all the complex human traits studied. Height, weight, bone mineral density (BMD), and bone size are all influenced by genetic and environmental factors as well as interactions between them. Height and weight are often used in population association studies to adjust the bone phenotypes. However, it is still unknown what proportion of genetic and environmental variability is shared between these anthropometric characteristics and the bone phenotypes. In the present study, our primary aims are: 1) Using quantitative transmission disequilibrium test (QTDT), we tested the association and/or linkage of the estrogen receptor α (ER-α ) (including PvwII, XbaI), alpha2-HS glycoprotein (AHSG) (including Nlalll, SacI), and transforming growth factor beta 1 (TGF- β1) genes (including single marker and haplotypes reconstructed by the markers within each gene) with bone mineral density (BMD) at the sites of lumbar spine and total hip in a sample of a total of 665 subjects from 157 Caucasian nuclear families; 2)Using SOLAR, we performed linkage exclusion analyses to test against the significance of two candidate regions (6q24-25 and 7q31.3-36) for height in an extended sample of 79 Caucasian pedigrees with 1,816 subjects; 3) The genetic and environmental correlations between the bone phenotypes (BMD and bone size at the lumbar spine and total hip and anthropometric indices (height and weight) in Chinese were studied using a bivariate quantitative genetic analysis and a sample of 931 healthy subjects from 292 Chinese nuclear families aged from 19 to 79 years old. Our results showed as follows: 1) Within-family associations were found between spine BMD and AHSG NlaIII (p=0.036), spine BMD and AHSG SacI (P=0.005), hip BMD and TGF- β1 BstuI (P=0.035), spine BMD and the haplotype NS (P=0.009) and haplotype ns (p=0.012) of AHSG. The positive within family associations were confirmed by 1000 times of permutations; 2) The two regions, 6q24-25 and 7q31.3-36, were excluded at a relative effect size of 10% or greater (p...