Genomic regions identified for BMD in a large sample including epistatic interactions and gender-specific effects

A genome-wide linkage scan was conducted using a large white sample to identify QTLs for BMD. We found QTLs in the total sample and the gender-specific subgroups, as well as significant epistatic interactions underlying BMD variations. Introduction: Low BMD is an important risk factor for osteoporosis and under strong genetic control. Materials and Methods: To identify quantitative trait loci (QTLs) for regulation of BMD, we performed a large-scale whole genome linkage scan (WGS) involving 4126 individuals from 451 families. In addition to the conventional linkage analyses in the total combined sample of males and females, we conducted epistatic interaction analyses and gender-specific linkage analyses. Results: Significant linkage was detected on 5q23 for wrist BMD (LOD = 3.39) and 15q13 for female spine BMD (LOD = 4.49). For spine BMD, we revealed significant epistatic interactions between 3p25 and 2q32 (p = 0.0022) and between 3p25 and 11q23 (p = 0.0007). We replicated several genomic regions that showed linkage with BMD in previous studies by others and ours, such as 3p21, 1p36, and Xq27. Conclusions: This study highlights the importance of large sample size, incorporation of epistatic interaction, and consideration of gender-specific effects in identifying QTLs for BMD variation. The results of this study provide a foundation for the future fine mapping and gene identification in our population.