• mtSNP;
  • haplogroup;
  • osteoporosis;
  • BMD;
  • association


Mitochondrial DNA (mtDNA) variants are involved in the pathogenesis of human complex diseases, especially for age-related disorders, including osteoporosis. However, the role of mtDNA variants in osteoporosis is largely unknown. In this study, we performed a mitochondria-wide association study for osteoporosis in a large sample of 2286 unrelated Caucasian subjects. A total of 445 mtSNPs were genotyped and 72 mtSNPs survived the quality control. We first examined association between mtSNPs and bone mineral density (BMD), and identified that an mtSNP, mt4823 within the ND2 gene, was strongly associated with hip BMD (P= 2.05 × 10−4), even after Bonferroni correction. The C allele of mt4823 was associated with reduced hip BMD and the effect size (β) was ∼0.044. Another SNP mt15885 within the MT-CYB gene was associated both with spine (P= 1.66 × 10−3) and hip BMD (P= 0.023). The T allele of mt15885 had a protective effect on spine (β= 0.064) and hip BMD (β= 0.038). Next, we classified subjects into the nine common European haplogroups and conducted association analyses. Subjects classified as haplogroup X had significantly lower hip BMD values than others (P= 0.040). Our results highlighted the importance of mtDNA variants in osteoporosis.