{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,26]],"date-time":"2026-08-26T05:20:33Z","timestamp":1787721633121,"version":"build-2784847793"},"reference-count":64,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"13","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2026,7,7]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">Genetics and environmental factors contribute to obesity risk, but the extent to which healthy behaviors can offset genetic susceptibility remains unclear. We examined the interaction between obesity polygenic risk and a composite healthy lifestyle score on body mass index (BMI) trajectories in women and men.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p xml:lang=\"en\">We analyzed 13\u2009780 women from the Nurses' Health Study and 8242 men from the Health Professionals Follow\u2010Up Study, all of European ancestry and free of major chronic disease at baseline. The lifestyle score comprised American Heart Association Essential 8 components (nonsmoking, physical activity, healthy eating, adequate sleep) plus moderate alcohol intake, modeled as a time\u2010varying variable. A genome\u2010wide polygenic score for BMI was derived from genome\u2010wide association study. Adjusted linear mixed\u2010effects models estimated associations and interactions on biennial BMI measures over up to 26\u2009years.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Each SD increase in the polygenic score was associated with 1.80\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (95% CI, 1.72\u20131.87) and 1.12\u2009kg\/m\n                      <jats:sup>2<\/jats:sup>\n                      (95% CI, 1.06\u20131.19) higher BMI in women and men, respectively. Significant interactions between the polygenic score and healthy lifestyle score (both\n                      <jats:italic toggle=\"no\">P<\/jats:italic>\n                      &lt;0.05) showed a dose\u2013response attenuation of the genetic effects with healthier lifestyles. Comparing the healthiest with the least healthy lifestyle groups, genetic effects on BMI were 35% lower in women and 28% lower in men. In sensitivity analyses, higher diet quality and physical activity consistently attenuated genetic associations in both cohorts, whereas current smoking showed similar effects in women only.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">Adherence to a healthier lifestyle attenuated the association between obesity polygenic risk and BMI in a dose\u2013response manner.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.126.049396","type":"journal-article","created":{"date-parts":[[2026,6,23]],"date-time":"2026-06-23T10:37:15Z","timestamp":1782211035000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Obesity Polygenic Risk and Healthy Lifestyle Interactions on Weight Trajectories in Women and Men"],"prefix":"10.1161","volume":"15","author":[{"given":"Aishi","family":"Ghosh","sequence":"first","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meghan","family":"Lau","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-8381-5819","authenticated-orcid":false,"given":"Anika","family":"Fernandes","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1424-0673","authenticated-orcid":false,"given":"Brian E.","family":"Cade","sequence":"additional","affiliation":[{"name":"Broad Institute","place":["Cambridge, 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USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richa","family":"Saxena","sequence":"additional","affiliation":[{"name":"Massachusetts General Hospital and Harvard Medical School","place":["Boston, USA"]},{"name":"Massachusetts General Hospital and Harvard Medical School","place":["Boston, USA"]},{"name":"Broad Institute","place":["Cambridge, USA"]},{"name":"Harvard Medical School","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8420-9167","authenticated-orcid":false,"given":"Tianyi","family":"Huang","sequence":"additional","affiliation":[{"name":"Harvard Medical School","place":["Boston, USA"]},{"name":"Brigham and Women's Hospital and Harvard Medical School","place":["Boston, USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1650-679X","authenticated-orcid":false,"given":"Hassan 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