{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,12]],"date-time":"2026-08-12T06:28:42Z","timestamp":1786516122851,"version":"build-2736575974"},"reference-count":48,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T00:00:00Z","timestamp":1785542400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515140062"],"award-info":[{"award-number":["2023A1515140062"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,8,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    This study aims to investigate the association between domestic water hardness and the risk of severe metabolic dysfunction\u2010associated steatotic liver disease (MASLD) and to assess the potential modifying role of genetic susceptibility. The UK Biobank is a prospective cohort study that recruited over 500,000 participants across the United Kingdom between 2006 and 2010. Domestic water hardness was assessed based on calcium carbonate (CaCO\n                    <jats:sub>3<\/jats:sub>\n                    ) concentration. Severe MASLD was defined using ICD\u201010 codes and death registry data. A polygenic risk score (PRS) for severe MASLD was constructed using 61 single nucleotide polymorphisms (SNPs) and divided into tertiles (low, intermediate, high risk). Cox proportional hazards regression models and restricted cubic spline analyses were employed. A total of 7039 incident severe MASLD cases (1.5%) were documented during a mean 13.8\u2010year follow\u2010up. Compared to water hardness &lt;\u2009100 mg\/L, individuals with domestic water hardness of 100\u2013200\u2009mg\/L were associated with a 22% lower risk of severe MASLD (HR 0.78, 95% CI 0.72\u20130.86), while water hardness &gt;\u2009200\u2009mg\/L was associated with an 11% higher risk (HR 1.11, 95% CI 1.05\u20131.16). A non\u2010linear relationship was observed between water hardness and severe MASLD incidence (\n                    <jats:italic>p<\/jats:italic>\n                    for non\u2010linear &lt;\u20090.001). The association did not significantly differ across strata of genetic susceptibility (\n                    <jats:italic>p<\/jats:italic>\n                    \u2010interaction &gt;\u20090.05). The study revealed a\n                    <jats:italic>U<\/jats:italic>\n                    \u2010shaped relationship between water hardness and severe MASLD, which was robust to genetic risk. An optimal water hardness range (100\u2013200\u2009mg\/L) may serve as a modifiable environmental factor for the prevention of severe MASLD.\n                  <\/jats:p>","DOI":"10.1096\/fj.202601814rr","type":"journal-article","created":{"date-parts":[[2026,8,1]],"date-time":"2026-08-01T09:43:20Z","timestamp":1785577400000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Associations Between Domestic Water Hardness, Genetic Risk and Severe\n                    <scp>MASLD<\/scp>\n                    : A Large\u2010Scale Cohort Study"],"prefix":"10.1096","volume":"40","author":[{"given":"Xiaoyu","family":"Zhao","sequence":"first","affiliation":[{"name":"Health Management Center The Eighth Affiliated Hospital, Southern Medical University (The First People's Hospital of Shunde, Foshan)  Foshan 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