Loci for regulation of bone mineral density in men and women identified by genome wide linkage scan: the FAMOS study

Abstract

Osteoporosis is a common disease with a strong genetic component, characterized by reduced bone mass and an increased risk of fracture. Bone mineral density (BMD) is a highly heritable trait and a key determinant of osteoporotic fracture risk, but the genes responsible are incompletely defined. Here, we identified quantitative trait loci (QTL) for regulation of BMD by a genome wide scan involving 3691 individuals from 715 families, who were selected because of reduced BMD values at the lumbar spine (LS-BMD) or femoral neck (FN-BMD) in probands. Linkage analysis was conducted in the study group as a whole with correction for age, gender, weight and height. Further analyses were conducted for men and women separately to identify gender-specific QTL and for those under and over the age of 50 years to distinguish QTL for peak bone mass from those that influence bone mass in older people. No regions of suggestive or significant linkage were identified when data from all subjects were analyzed together. On subgroup analysis, however, we identified a significant QTL for FN-BMD on chromosome 10q21 (LOD score +4.42; men < or =50 years) and two suggestive QTL for LS-BMD on chromosomes 18p11 (LOD score +2.83; women >50 years) and 20q13 (LOD score +3.20; women < or =50 years). We identified five other QTL for BMD with LOD scores of greater than +2.20 on chromosomes 3q25, 4q25, 7p14, 16p13 and 16q23. This study provides evidence for gender-specific, site-specific and age-specific QTL, which regulate BMD in humans, and illustrates the importance of conducting subgroup analysis to detect these loci.

Densidade mineral óssea associada a características físicas e estilo de vida em adolescentes

“…The Brazilian population was composed of mixing of Europeans, Africans and native Brazilians, where an individual classified as white, according to many phenotype characteristics, presents African heredity, while another classified as black, presents . Moreover, the genes related to the BMD variation usually specifically act according to race, age and sex 21 and the BMD variation may be influenced by genetic heredity 22 . Thus, the results found in the present study suggest that the BMD stratification of Brazilian girls by race, simply considering phenotype traits, may present inaccurate results, and while studies comparing the BMD of girls and women stratified according to genetic heredity markers are not conducted, it will be impossible to understand the correlation between race and BMD in the Brazilian population.…”

Contribution of Myostatin gene polymorphisms to normal variation in lean mass, fat mass and peak BMD in Chinese male offspring

“…Studies in humans have also revealed a gender difference in the degree of heritability of BMD at specific skeletal sites [24][25][26] . Ralston et al [27] provided evidence for gender-specific, site-specific and age-specific QTLs that regulate BMD in humans. However, exactly which gene is responsible for the differences observed between the males and females is still unclear.…”

Conteúdo e densidade mineral óssea de adolescentes do sexo feminino. DOI: 10.5007/1980-0037.2011v13n5p354

“…However, in contrast to other countries, the classification of the Brazilian population according to race using only phenotypic characteristics is difficult, mainly because of the interethnic admixed between Europeans, Africans and Amerindians, in which one individual classified as white, according to phenotypic characteristics, can have African ancestry and another classified as black can have European one 26 . There is little information about the mechanisms by which ethnicity influences BMD, but it is known that genes related to variations in BMD are race, age and gender specific 27 and that BMD is influenced by genetic ancestry 28 . In a study evaluating BMD in Afro-American women, European genetic ancestry seen in part of the sample was negatively correlated with BMD 28 .…”