Impact of Genetic Predisposition to Obesity on Long‐Term Maintenance of Modest Weight Loss in Postmenopausal Women
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| Formato: | Artículo Open Access |
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Wiley
2026
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| _version_ | 1867016216492638208 |
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| author | Harold H. Lee Christy L. Avery Misa Graff Daeeun Kim Josh Arias Linda Van Horn Charles Kooperberg Kari E. North |
| author_facet | Harold H. Lee Christy L. Avery Misa Graff Daeeun Kim Josh Arias Linda Van Horn Charles Kooperberg Kari E. North Harold H. Lee Christy L. Avery Misa Graff Daeeun Kim Josh Arias Linda Van Horn Charles Kooperberg Kari E. North |
| collection | Wiley Open Access |
| contents | Impact of Genetic Predisposition to Obesity on Long‐Term Maintenance of Modest Weight Loss in Postmenopausal Women Harold H. Lee Christy L. Avery Misa Graff Daeeun Kim Josh Arias Linda Van Horn Charles Kooperberg Kari E. North Obesity ABSTRACT Objective Long‐term weight regain limits the population‐level benefits of obesity interventions. We tested whether the polygenic risk score of BMI (PRS BMI ) modifies weight trajectories following modest weight loss. Methods The analytic sample included 9897 postmenopausal women from the Women's Health Initiative Dietary Modification Trial (6132 European American; 3749 African American). PRS BMI was derived from a trans‐ancestry GWAS of ~2 million participants. Longitudinal weight change (7 years) was modeled using weighted GEE. Results In European Americans, the PRS BMI × randomization × time interactions approached significance at the 95th percentile ( p = 0.052) and 85th percentile ( p = 0.07). No interaction was observed in African Americans. In analyses restricted to European Americans who lost ≥ 5% of initial weight by year 1 (20%; n = 1273), women in the ≥ 95th percentile of PRS BMI regained nearly twice as much per year as those with average risk (0.94 vs. 0.48 kg/year, p = 0.0016). Conclusions A high PRS BMI was associated with faster weight regain following modest weight loss in European American women. While further validation is required in a diverse population, these results suggest the potential for genetics to inform targeted strategies for sustaining long‐term weight management. Trial Registration ClinicalTrials.gov identifier: 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005 10.1002/oby.70175 http://creativecommons.org/licenses/by/4.0/ |
| doi_str_mv | 10.1002/oby.70175 |
| format | Artículo Open Access |
| id | wiley_oa_10_1002_oby_70175 |
| institution | Wiley Open Access |
| license_str_mv | http://creativecommons.org/licenses/by/4.0/ |
| publishDate | 2026 |
| publisher | Wiley |
| record_format | wiley_oa |
| spellingShingle | Impact of Genetic Predisposition to Obesity on Long‐Term Maintenance of Modest Weight Loss in Postmenopausal Women Harold H. Lee Christy L. Avery Misa Graff Daeeun Kim Josh Arias Linda Van Horn Charles Kooperberg Kari E. North Obesity Impact of Genetic Predisposition to Obesity on Long‐Term Maintenance of Modest Weight Loss in Postmenopausal Women Harold H. Lee Christy L. Avery Misa Graff Daeeun Kim Josh Arias Linda Van Horn Charles Kooperberg Kari E. North Obesity ABSTRACT Objective Long‐term weight regain limits the population‐level benefits of obesity interventions. We tested whether the polygenic risk score of BMI (PRS BMI ) modifies weight trajectories following modest weight loss. Methods The analytic sample included 9897 postmenopausal women from the Women's Health Initiative Dietary Modification Trial (6132 European American; 3749 African American). PRS BMI was derived from a trans‐ancestry GWAS of ~2 million participants. Longitudinal weight change (7 years) was modeled using weighted GEE. Results In European Americans, the PRS BMI × randomization × time interactions approached significance at the 95th percentile ( p = 0.052) and 85th percentile ( p = 0.07). No interaction was observed in African Americans. In analyses restricted to European Americans who lost ≥ 5% of initial weight by year 1 (20%; n = 1273), women in the ≥ 95th percentile of PRS BMI regained nearly twice as much per year as those with average risk (0.94 vs. 0.48 kg/year, p = 0.0016). Conclusions A high PRS BMI was associated with faster weight regain following modest weight loss in European American women. While further validation is required in a diverse population, these results suggest the potential for genetics to inform targeted strategies for sustaining long‐term weight management. Trial Registration ClinicalTrials.gov identifier: 75N92021D00001, 75N92021D00002, 75N92021D00003, 75N92021D00004, and 75N92021D00005 10.1002/oby.70175 http://creativecommons.org/licenses/by/4.0/ |
| title | Impact of Genetic Predisposition to Obesity on Long‐Term Maintenance of Modest Weight Loss in Postmenopausal Women |
| topic | Obesity |
| url | https://onlinelibrary.wiley.com/doi/10.1002/oby.70175 |