We focus on the identification of genetic susceptibility variants associ-22In 2021, we expanded the biological associations of somatic chromosomal alterations in autosomes (mosaic chromosomal alterations, mCAs) from DNA microarray data. We reported that mCAs are a risk for infection or severity of infection including with SARS-CoV-2 and that mCAs and clonal hemato-poiesis with point mutations synergistically increase the risk of blood cancers. These findings illustrate how critical somatic mutations are for diseases and phenotypes and how important it is to take acquired (non-innate) and dynamic components into consideration to evaluate human health and predict future outcomes. Our lab played central roles in genetic analyses of atopic dermatitis, systemic lupus erythematosus, epilepsia, and adolescent idiopathic scoliosis. Especially for atopic dermatitis, we successfully fine-mapped the CCDC80 locus using our own machine-learning-based transcription prediction method, MENTR, to reveal a causal variant that would alter an enhancer level in skin-relevant tissues/cells. This prediction was experimentally validated. We also contributed to four big papers in Nature and Cell – genetic studies of ovarian aging, osteoarthritis and lipids, and an expression quantitative trait loci study of comprehensive white blood cell subpopulations.We are moving into two new major research fields. One is to focus on somatic events and to use whole-genome sequencing analysis to detect rare variants, which represent strong candidates to explain population differences in the genet-ics of the traits, especially somatic events. The second is to employ deep learning techniques to predict the biological consequences of trait-relevant variants.ated with complex traits and on understanding their biological roles by using integrative analyses of epigenome, transcriptome and chromatin accessi-bility data. We are also interested in acquired mutations as strong driving forces of phenotypes. We will then deliver these genetic findings to patients as part of our ongoing translational research efforts.Figure: Successful fine-mapping of the CCDC80 region in atopic dermatitisMENTR, our own prediction method of transcripts including non-coding RNA based on machine-learning, could pinpoint the causal variant altering enhancer RNA levels in Langerhans cells and skin epidermis.Recent Major PublicationsTanaka N, Koido M, Suzuki A, Otomo N, Suetsugu H, Kochi Y, Tomizuka K, Momozawa Y, Kamatani Y; Biobank Japan Project, Ikegawa S, Yamamoto K, Terao C*. Eight novel susceptibility loci and putative causal variants in atopic dermatitis. J Allergy Clin Immunol 148, 1293-1306 (2021)Boer CG, Hatzikotoulas K, Southam L, Stefánsdóttir L, Zhang Y, Coutinho de Almeida R, Wu TT, Zheng J, Hartley A, Teder-Laving M, Skogholt AH, Terao C, Zengini E, Alexiadis G, Barysenka A, Bjornsdottir G, Gabrielsen ME, Gilly A, Ingvarsson T, Johnsen MB, Jonsson H, Kloppenburg M, Luetge A, Lund SH, Mägi R, Mangino M, Nelissen RRGHH, Shivakumar M, Steinberg J, Takuwa H, Thomas LF, Tuer-lings M; arcOGEN Consortium; HUNT All-In Pain; ARGO Consortium; Regeneron Genetics Center, Babis GC, Yin Cheung JP, Kang JH, Kraft P,… Ikegawa S, Hveem K, Esko T, Wilkinson JM, Meulenbelt I, Michael Lee MT, van Meurs JBJ, Styrkársdóttir U, Zeggini E. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell 184, 6003-6005 (2021)Yin X, Kim K, Suetsugu H, Bang SY, Wen L, Koido M, Ha E, Liu L, Sakamoto Y, Jo S, Leng RX, Otomo N, …Suzuki A, Sumida T, Okada Y, Matsuda K, Matsuo K, Kochi Y; Japanese Research Committee on Idiopathic Osteone-crosis of the Femoral Head, Kottyan LC, Weirauch MT, Parameswaran S, Eswar S, Salim H, Chen X, Yamamoto K, Harley JB, Ohmura K, Kim TH, Yang S, Yamamoto T, Kim BJ, Shen N, Ikegawa S, Lee HS, Zhang X, Terao C*, Cui Y, Bae SC. Meta-analysis of 208370 East Asians identifies 113 susceptibility loci for systemic lupus erythematosus. Ann Rheum Dis 80, 632-640 (2021)Invited presentationsTerao C. “Clarification of the mechanism underlying leuke-mia using SNP array data” TCCSG webinar (Tokyo, Japan/Online) July 2021Terao C. “Research on rheumatic diseases with a view to clinical application” The 9th Yokohama-Kawasaki Rheu-matism Wakakusa/Cosmos Meeting (Tokyo, Japan) June 2021Terao C. “Construction of database and analyses of data for rheumatic diseases under the viewpoint of physician scientist” Meet the Expert, Japanese College of Rheuma-tology (JCR) symposium (Japan/Online) April 2021Terao C. “Genetic basis on clonal hematopoiesis” The 3rd Fukushima Onco-Cardiology Research Meeting (Fuku-shima Japan) March 2021Terao C. “Genetics disentangling the basics of rheumatoid arthritis and autoimmune diseases” The 11th Rheumatol-ogy Education Inter League REIL (Osaka, Japan) January 2021Laboratory for Statistical and Translational GeneticsTeam Leader: Chikashi Terao
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