{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:39:23Z","timestamp":1792093163135,"version":"4.4.0"},"reference-count":50,"publisher":"American Diabetes Association","issue":"7","license":[{"start":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T00:00:00Z","timestamp":1707696000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.diabetesjournals.org\/journals\/pages\/license"}],"funder":[{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["1K08HG010155"],"award-info":[{"award-number":["1K08HG010155"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000051","name":"National Human Genome Research Institute","doi-asserted-by":"publisher","award":["1U01HG011719"],"award-info":[{"award-number":["1U01HG011719"]}],"id":[{"id":"10.13039\/100000051","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100013915","name":"Sarnoff Cardiovascular Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100013915","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["diabetesjournals.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2024,7,1]]},"abstract":"<jats:sec>\n                  <jats:title\/>\n                  <jats:p>Familial partial lipodystrophy (FPLD) is a heterogenous group of syndromes associated with a high prevalence of cardiometabolic diseases. Prior work has proposed DEXA-derived fat mass ratio (FMR), defined as trunk fat percentage divided by leg fat percentage, as a biomarker of FPLD, but this metric has not previously been characterized in large cohort studies. We set out to 1) understand the cardiometabolic burden of individuals with high FMR in up to 40,796 participants in the UK Biobank and 9,408 participants in the Fenland study, 2) characterize the common variant genetic underpinnings of FMR, and 3) build and test a polygenic predictor for FMR. Participants with high FMR were at higher risk for type 2 diabetes (odds ratio [OR] 2.30, P = 3.5 \u00d7 10\u221241) and metabolic dysfunction\u2013associated liver disease or steatohepatitis (OR 2.55, P = 4.9 \u00d7 10\u22127) in UK Biobank and had higher fasting insulin (difference 19.8 pmol\/L, P = 5.7 \u00d7 10\u221236) and fasting triglycerides (difference 36.1 mg\/dL, P = 2.5 \u00d7 10\u221228) in the Fenland study. Across FMR and its component traits, 61 conditionally independent variant-trait pairs were discovered, including 13 newly identified pairs. A polygenic score for FMR was associated with an increased risk of cardiometabolic diseases. This work establishes the cardiometabolic significance of high FMR, a biomarker for FPLD, in two large cohort studies and may prove useful in increasing diagnosis rates of patients with metabolically unhealthy fat distribution to enable treatment or a preventive therapy.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Article Highlights<\/jats:title>\n               <\/jats:sec>","DOI":"10.2337\/db23-0575","type":"journal-article","created":{"date-parts":[[2024,2,12]],"date-time":"2024-02-12T17:05:23Z","timestamp":1707757523000},"page":"1099-1111","update-policy":"https:\/\/doi.org\/10.2337\/ada-journal-policies","source":"Crossref","is-referenced-by-count":24,"title":["Relationship of Fat Mass Ratio, a Biomarker for Lipodystrophy, With Cardiometabolic Traits"],"prefix":"10.2337","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2535-4759","authenticated-orcid":false,"given":"Saaket","family":"Agrawal","sequence":"first","affiliation":[{"name":"1Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, MA"},{"name":"2Department of Medicine, Massachusetts General Hospital, Boston, MA"},{"name":"3Department of Medicine, Harvard Medical School, Boston, MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian\u2019an","family":"Luan","sequence":"additional","affiliation":[{"name":"4MRC Epidemiology Unit, Institute of Metabolic Science, University of Cambridge, Cambridge Biomedical Campus, Cambridge, U.K."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Beryl B.","family":"Cummings","sequence":"additional","affiliation":[{"name":"5Marea Therapeutics, San Francisco, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ethan 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