{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,19]],"date-time":"2026-06-19T10:51:13Z","timestamp":1781866273955,"version":"3.54.5"},"reference-count":58,"publisher":"The Endocrine Society","issue":"2","license":[{"start":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T00:00:00Z","timestamp":1711497600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Scientific Foundation of China","doi-asserted-by":"publisher","award":["81922059"],"award-info":[{"award-number":["81922059"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Scientific Foundation of China","doi-asserted-by":"publisher","award":["2021JCW-08"],"award-info":[{"award-number":["2021JCW-08"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,1,21]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:sec>\n                  <jats:title>Background<\/jats:title>\n                  <jats:p>Bone mineral density (BMD) is a major predictor of osteoporotic fractures, and previous studies have reported the effects of mitochondrial dysfunction and lifestyle on BMD, respectively. However, their interaction effects on BMD are still unclear.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Objective<\/jats:title>\n                  <jats:p>We aimed to investigate the possible interaction of mitochondrial DNA (mtDNA) and common lifestyles contributing to osteoporosis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>Our analysis included 119 120 white participants (Nfemale = 65 949 and Nmale = 53 171) from the UK Biobank with heel BMD phenotype data. A generalized linear regression model of PLINK was performed to assess the interaction effects of mtDNA and 5 life environmental factors on heel BMD, including smoking, drinking, physical activity, dietary diversity score, and vitamin D. In addition, we also performed linear regression analysis for total body BMD. Finally, we assessed the potential causal relationships between mtDNA copy number (mtDNA-CN) and life environmental factors using Mendelian randomization (MR) analysis.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>Our study identified 4 mtDNA loci showing suggestive evidence of heel BMD, such as m.16356T&amp;gt;C (MT-DLOOP; P = 1.50 \u00d7 10\u22123) in total samples. Multiple candidate mtDNA \u00d7 lifestyle interactions were also detected for heel BMD, such as MT-ND2 \u00d7 physical activity (P = 2.88 \u00d7 10\u22123) in total samples and MT-ND1 \u00d7 smoking (P = 8.54 \u00d7 10\u22124) in males. Notably, MT-CYB was a common candidate mtDNA loci for heel BMD to interact with 5 life environmental factors. Multivariable MR analysis indicated a causal effect of physical activity on heel BMD when mtDNA-CN was considered (P = 1.13 \u00d7 10\u22123).<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Conclusion<\/jats:title>\n                  <jats:p>Our study suggests the candidate interaction between mtDNA and lifestyles on heel BMD, providing novel clues for exploring the pathogenesis of osteoporosis.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1210\/clinem\/dgae195","type":"journal-article","created":{"date-parts":[[2024,3,27]],"date-time":"2024-03-27T19:54:01Z","timestamp":1711569241000},"page":"e339-e346","source":"Crossref","is-referenced-by-count":4,"title":["Assessing the Interaction Effects of Mitochondrial DNA Polymorphisms and Lifestyle on Heel Bone Mineral Density"],"prefix":"10.1210","volume":"110","author":[{"given":"Dan","family":"He","sequence":"first","affiliation":[{"name":"Key Laboratory of Trace Elements and Endemic 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