美国宾夕法尼亚大学Kyong-Mi Chang、Benjamin F. Voight等研究人员合作发现,不明原因的慢性ALT升高可作为非酒精性脂肪肝替代指标。这一研究成果于2022年6月2日在线发表在国际学术期刊《自然—遗传学》上。
Author: Vujkovic, Marijana, Ramdas, Shweta, Lorenz, Kim M., Guo, Xiuqing, Darlay, Rebecca, Cordell, Heather J., He, Jing, Gindin, Yevgeniy, Chung, Chuhan, Myers, Robert P., Schneider, Carolin V., Park, Joseph, Lee, Kyung Min, Serper, Marina, Carr, Rotonya M., Kaplan, David E., Haas, Mary E., MacLean, Matthew T., Witschey, Walter R., Zhu, Xiang, Tcheandjieu, Catherine, Kember, Rachel L., Kranzler, Henry R., Verma, Anurag, Giri, Ayush, Klarin, Derek M., Sun, Yan V., Huang, Jie, Huffman, Jennifer E., Townsend Creasy, Kate, Hand, Nicholas J., Liu, Ching-Ti, Long, Michelle T., Yao, Jie, Budoff, Matthew, Tan, Jingyi, Li, Xiaohui, Lin, Henry J., Chen, Yii-Der Ida, Taylor, Kent D., Chang, Ruey-Kang, Krauss, Ronald M., Vilarinho, Silvia, Brancale, Joseph, Nielsen, Jonas B., Locke, Adam E., Jones, Marcus B., Verweij, Niek, Baras, Aris, Reddy, K. Rajender, Neuschwander-Tetri, Brent A., Schwimmer, Jeffrey B., Sanyal, Arun J., Chalasani, Naga, Ryan, Kathleen A., Mitchell, Braxton D., Gill, Dipender, Wells, Andrew D., Manduchi, Elisabetta, Saiman, Yedidya, Mahmud, Nadim, Miller, Donald R., Reaven, Peter D., Phillips, Lawrence S., Muralidhar, Sumitra
Issue&Volume: 2022-06-02
Abstract: Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P<5 × 108). External replication in histology-defined NAFLD cohorts (7,397 cases and 56,785 controls) or radiologic imaging cohorts (n=44,289) replicated 17 single-nucleotide polymorphisms (SNPs) (P<6.5 × 104), of which 9 were new (TRIB1, PPARG, MTTP, SERPINA1, FTO, IL1RN, COBLL1, APOH and IFI30). Pleiotropy analysis showed that 61 of 77 multiancestry and all 17 replicated SNPs were jointly associated with metabolic and/or inflammatory traits, revealing a complex model of genetic architecture. Our approach integrating cALT, histology and imaging reveals new insights into genetic liability to NAFLD.
DOI: 10.1038/s41588-022-01078-z
Source: https://www.nature.com/articles/s41588-022-01078-z
Nature Genetics:《自然—遗传学》,创刊于1992年。隶属于施普林格·自然出版集团,最新IF:25.455
官方网址:https://www.nature.com/ng/
投稿链接:https://mts-ng.nature.com/cgi-bin/main.plex