Genetic and Environmental Determinants of Volumetric and Areal BMD in Multi-Generational Families of African Ancestry: The Tobago Family Health Study

Abstract

BMD is higher and fracture risk is lower among individuals of African versus European descent, but little is known about the genetic architecture of BMD in the former group. Heritabilities of areal and volumetric BMD were moderate in our large families of African descent but differed for trabecular and cortical BMD.Introduction: Populations of African ancestry have lower osteoporotic fracture risk and higher BMD than other ethnic groups. However, there is a paucity of information regarding the genetic and environmental influences on bone health among populations of African heritage. Materials and Methods:We dissected the genetic architecture of areal BMD measured by DXA at the proximal femur, lumbar spine, and whole body and volumetric BMD measured by pQCT at the distal and proximal radius and tibia in 283 women and 188 men Ն18 years of age (mean, 43 years) from eight multigenerational Afro-Caribbean families (mean family size > 50). Using quantitative genetic methods, we estimated the residual heritability and the effects of anthropometric, demographic, lifestyle, and medical variables on areal and volumetric BMD. Results: Compared with U.S. non-Hispanic blacks and whites, areal BMD at the femoral neck was highest in the Afro-Caribbean men and women at all ages. Trabecular volumetric BMD decreased linearly with increasing age, whereas cortical volumetric BMD did not decrease until age 40-49, especially in women. Anthropometric, lifestyle, and medical factors accounted for 12-32% of the variation in areal and volumetric BMD, and residual heritabilities (range, 0.23-0.52) were similar to those reported in other ethnic groups. Heritability of cortical BMD was substantially lower than that of areal or trabecular volumetric BMD, although the measured covariates accounted for a similar proportion of the total phenotypic variation. Conclusions: Our study is the first comprehensive genetic epidemiologic analysis of volumetric BMD measured by QCT and the first analysis of these traits in extended families of African descent. Genes account for as much or more of the total variation in areal and volumetric BMD than do environmental factors, but these effects seem to differ for trabecular and cortical bone.

Genetic influences on bone loss in the San Antonio Family Osteoporosis study

“…Numerous family and sibling studies of peak BMD have been performed in a variety of populations, and these studies have universally shown the high heritability of peak BMD [3,8,21,29,30]. Many whole genome linkage scans have also been performed, with QTLs reported at a number of chromosomal regions, though specific QTLs have rarely been replicated across studies [5][6][7]28,[31][32][33][34][35][36], probably due, in part, to genetic heterogeneity among the populations studied.…”

Correlates of bone mineral density among postmenopausal women of African Caribbean ancestry: Tobago women's health study

“…This high BMD potential may not be realized among native Africans due to nutritional and lifestyle factors [12]. It is reasonable to consider that the lower levels of genetic European and East Indian admixture among Tobagonian women, in the context of better nutrition and lifestyle factors, may be a possible reason for the higher BMD that we observed in this analysis compared to American Blacks, where European admixture is more prevalent [7,21,27,28].…”

“…Reference data did not allow for direct comparison of volumetric BMD [4], which takes bone depth into consideration, between Tobagonian and U.S. women. Research suggests that people of African ancestry may have genetic potential for higher BMD compared to people of European ancestry [7,27]. This high BMD potential may not be realized among native Africans due to nutritional and lifestyle factors [12].…”

“…It is well established that Black Americans have greater BMD across the entire life span compared to White Americans [3][4][5][6][7], which maybe due in part to higher peak bone mass, body size, and slower rates of bone loss [3,[8][9][10][11]. Although Black American women have considerably higher BMD than White American women, this is not the case for all women of African ancestry.…”

Implementing an intervention to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia: BONEII, a prospective placebo-controlled double-blind randomized interventional longitudinal study design

“…Because bone mineralization results from a complex interaction of genetic programming [27] and environmental and lifestyle factors [28,29], primary endpoints of BONEII include pharmacogenetic and bone metabolic biomarkers, lifestyle assessment, nutritional intake, and medical history.…”