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LTPA was categorised into cohort\u2010specific quartiles; MVLTPA in 0, &lt;\u2009100, &lt;\u2009200, and \u2265\u2009200 METs\u2010min\/day. In one\u2010sample Mendelian randomisation analyses, we categorised participants in quartiles of a cardiorespiratory fitness polygenic risk score derived from a large GWAS in UK Biobank. Group\u2010dependent BMI trajectories were modelled using spline mixed\u2010effects models. Obesity onset (first BMI \u2265\u200930\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      ) was analysed with IPW\u2010weighted Kaplan\u2013Meier curves and Cox models.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Higher LTPA was associated with slower BMI increases in ages 30\u201360 (Q1: +0.120 vs. Q4: +0.075\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \u00b7year), slower declines in ages 70\u201390 (Q1: \u22120.143 vs. Q4: \u22120.123\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \u00b7year), and lower obesity risk (Q4 vs. Q1: HR 0.83, 95% CI 0.72\u20130.96). Similar trends were observed for MVLTPA. Higher genetically determined cardiorespiratory fitness showed parallel gradients (ages 30\u201360, Q1: +0.109 vs. Q4: +0.101\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \u00b7year; ages 70\u201390, Q1: \u22120.130 vs. Q4: \u22120.102\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      \u00b7year) and lower obesity risk (Q4 vs. Q1: HR 0.66, 0.56\u20130.78). Associations were present for women and men separately, but were stronger in men.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Higher LTPA and MVLTPA were associated with more favourable lifelong BMI trajectories, delayed obesity risk, and convergent support from Mendelian randomisation analyses, supporting a causal protective role of physical activity (in both sexes but stronger in men).<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/dom.71090","type":"journal-article","created":{"date-parts":[[2026,7,10]],"date-time":"2026-07-10T03:16:28Z","timestamp":1783653388000},"page":"8925-8935","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Leisure\u2010Time Physical Activity on Age\u2010Modelled Trajectories of Body Mass Index and Obesity Risk Throughout Life: Multivariable Regression and Mendelian Randomization Analyses Using Electronic Health Record Data From the\n                    <scp>CORDELIA<\/scp>\n                    \u2010Catalunya Study"],"prefix":"10.1111","volume":"28","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6777-1649","authenticated-orcid":false,"given":"Javier","family":"Hernando\u2010Redondo","sequence":"first","affiliation":[{"name":"REGICOR Study Group Hospital del Mar Research Institute (HMRIB), Carrer del Doctor Aiguader  Barcelona Spain"},{"name":"Consorcio CIBER, M.P. 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