Our lab is interested in investigating the genetic background of diabetes 25and related metabolic traits that may help us better understand the un-derlying disease mechanisms. We have been focusing on investigating the ge-netic contribution to type 2 diabetes (T2D) susceptibility in the Japanese popu-lation by using the rich genetic resources generated by Biobank Japan (BBJ). By using the full BBJ collection, we conducted a single population Genome-wide association study (GWAS) of T2D in 191,764 Japanese. In addition to the then established >150 T2D loci, we identified 28 novel loci (publication 3). We joined this effort with our international collaborators in the Asian Genetic Epi-demiology Network for T2D (AGEN-T2D) to include 433,540 East Asian indi-viduals in the GWAS meta-analysis (publication 1). We identified 301 distinct association signals at 183 loci. Previously undescribed associations included signals in or near genes and a microRNA cluster that affect the differentiation of muscle and adipose tissues, which are essential in the development of T2D. Interestingly, expression quantitative trait loci at two overlapping T2D signals affect two genes in different tissues. Association studies in diverse populations demonstrated the benefit of identifying additional loci and elucidating disease-associated genes, biology and pathways.Figure: Effect size comparison of lead variants identified in the East Asin T2D GWAS BMI-un-adjusted meta-analysis and previous European T2D GWAS meta-analysisFor 332 unique lead variants identified from the BMI-unadjusted meta-analyses, per-allele effect sizes from the European meta-analysis (y axis) were plotted against per-allele effect sizes from our East Asian meta-analysis (x axis). Maximal effective sample sizes were Neff = 211,793 for East Asians and Neff = 231,436 for Europeans.Recent Major PublicationsSpracklen C.N.*, Horikoshi M*, Kim Y.J.*, Lin K*, Bragg F, Moon S, Suzuki K, Tam CHT, Tabara Y, Kwak SH, Takeuchi F, Long J, Lim VJY, Chai JF, Chen CH, Nakatochi M, Yao J, Choi HS, Iyengar AK, Perrin HJ, Brotman SM, van de Bunt M, Gloyn AL, Below JE, Boehnke M, Bowden DW, Chambers JC, Mahajan A, McCarthy MI, Ng MCY, Petty LE, Zhang W, Morris AP, Adair LS, Akiyama M, Bian Z, Chan JCN, Chang LC, Chee ML, Chen YI, Chen YT, Chen Z, Chuang LM, Du S, Gordon-Larsen P, Gross M, Guo X, Guo Y, Han S, Howard AG et al. Identification of type 2 diabetes loci in 433,540 East Asian individuals. Nature 582, 240-245 (2020)Warrington NM*, Beaumont RN*, Horikoshi M*, Day FR*, Helgeland Ø*, Laurin C, Bacelis J, Peng S, Hao K, Feenstra B, Wood AR, Mahajan A, Tyrrell J, Robertson NR, Rayner NW, Qiao Z, Moen GH, Vaudel M, Marsit CJ, Chen J, Nodzenski M, Schnurr TM, Zafarmand MH, Bradfield JP, Grarup N, Kooijman MN, Li-Gao R, Geller F, Ahluwalia TS, Paternoster L, Rueedi R, Huikari V, Hottenga JJ, Lyy-tikäinen LP, Cavadino A, Metrustry S, Cousminer DL, Wu Y, Thiering E, Wang CA, Have CT, Vilor-Tejedor N, Joshi PK, Painter JN, Ntalla I, Myhre R, Pitkänen N, van Leeuwen EM, Joro R, Lagou V et al. Maternal and fetal genetic effects on birth weight and their relevance to cardio-metabolic risk factors. Nat Genet 51, 804-814 (2019)Suzuki K, Akiyama M, Ishigaki K, Kanai M, Hosoe J, Shojima N, Hozawa A, Kadota A, Kuriki K, Naito M, Tanno K, Ishigaki Y, Hirata M, Matsuda K, Iwata N, Ikeda M, Sawada N, Yamaji T, Iwasaki M, Ikegawa S, Maeda S, Murakami Y, Wakai K, Tsugane S, Sasaki M, Yamamoto M, Okada Y, Kubo M, Kamatani Y#, Horikoshi M#, Yamauchi T#, Kadowaki T#. Identification of 28 new susceptibility loci for type 2 diabetes in the Japanese population. Nat Genet 51, 379-386 (2019)*These authors jointly contributed to the work.#Corresponding authorsLaboratory for Genomics of Diabetes and MetabolismTeam Leader: Momoko Horikoshi
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