{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T13:28:29Z","timestamp":1791379709478,"version":"4.3.3"},"reference-count":52,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T00:00:00Z","timestamp":1734480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,2,8]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Observational studies have reported a bidirectional correlation between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D), but the shared genetic basis between the two conditions remains unclear. Using genome-wide association study (GWAS) summary data from European-ancestry populations, we examined the cross-trait genetic correlation and identified genomic overlaps and shared risk loci. We employed a latent causal variable model and Mendelian randomization (MR) analysis to infer causal relationships. Colocalization analysis and conditional\/conjunctional false discovery rate (condFDR\/conjFDR) were used to identify genomic overlaps and shared risk loci. Two-step MR analysis was utilized to identify potential mediators. We observed a strong positive genomic correlation between NAFLD and T2D (rg\u2009=\u20090.652, P\u2009=\u20095.67\u2009\u00d7\u200910\u22126) and identified tissue-specific transcriptomic correlations in the pancreas, liver, skeletal muscle, subcutaneous adipose, and blood. Genetic enrichment was observed in NAFLD conditional on associations with T2D and vice versa, indicating significant polygenic overlaps. We found robust evidence for the causal effect of NAFLD on T2D, particularly insulin-related T2D, rather than vice versa. Colocalization analysis identified shared genomic regions between NAFLD and T2D, including GCKR, FTO, MAU2-TM6SF2, and PNPLA3-SAMM50. High-density lipoprotein cholesterol and insulin were partly mediated the association between NAFLD and T2D. These findings unveil a close genetic link between NAFLD and T2D, shedding light on the biological mechanisms connecting NAFLD progression to T2D.<\/jats:p>","DOI":"10.1093\/hmg\/ddae184","type":"journal-article","created":{"date-parts":[[2024,12,18]],"date-time":"2024-12-18T06:47:56Z","timestamp":1734504476000},"page":"338-346","source":"Crossref","is-referenced-by-count":6,"title":["Dissecting the shared genetic architecture between nonalcoholic fatty liver disease and type 2 diabetes"],"prefix":"10.1093","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5244-6894","authenticated-orcid":false,"given":"Zhenqiu","family":"Liu","sequence":"first","affiliation":[{"name":"State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University , 825 Zhangheng RD, Pudong New Area, Shanghai 201203 ,","place":["China"]},{"name":"Fudan University Taizhou Institute of Health Sciences , 799 Yaocheng RD, Taizhou 225316 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaochen","family":"Chen","sequence":"additional","affiliation":[{"name":"Clinical Research Institute, Shanghai Jiao Tong University School of Medicine , 227 Chongqing South RD, Shanghai 200025 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huangbo","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University , 825 Zhangheng RD, Pudong New Area, Shanghai 201203 ,","place":["China"]},{"name":"Fudan University Taizhou Institute of Health Sciences , 799 Yaocheng RD, Taizhou 225316 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jin","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University , 825 Zhangheng RD, Pudong New Area, Shanghai 201203 ,","place":["China"]},{"name":"Fudan University Taizhou Institute of Health Sciences , 799 Yaocheng RD, Taizhou 225316 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiejun","family":"Zhang","sequence":"additional","affiliation":[{"name":"Fudan University Taizhou Institute of Health Sciences , 799 Yaocheng RD, Taizhou 225316 ,","place":["China"]},{"name":"Key Laboratory of Public Health Safety, Fudan University, Ministry of Education , 130 Dong'an RD, Shanghai 200032 ,","place":["China"]},{"name":"Department of Epidemiology, School of Public Health, Fudan University , 130 Dong'an RD, Shanghai 200032 ,","place":["China"]},{"name":"Yiwu Research Institute of Fudan University , 2 Chengbei RD, Yiwu 322000 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingdong","family":"Chen","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Genetic Engineering and Human Phenome Institute, Fudan University , 825 Zhangheng RD, Pudong New Area, Shanghai 201203 ,","place":["China"]},{"name":"Fudan University Taizhou Institute of Health Sciences , 799 Yaocheng RD, Taizhou 225316 ,","place":["China"]},{"name":"Yiwu Research Institute of Fudan University , 2 Chengbei RD, Yiwu 322000 ,","place":["China"]},{"name":"National Clinical Research Center for Aging and Medicine, Huashan Hospital, Fudan University , 12 Urumqi RD, Shanghai 200040 ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2024,12,18]]},"reference":[{"key":"2025021107010451200_ref1","doi-asserted-by":"crossref","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","article-title":"The prevalence and incidence of NAFLD worldwide: a systematic review and meta-analysis","volume":"7","author":"Riazi","year":"2022","journal-title":"Lancet Gastroenterol 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