Search

Your search keyword '"Dong Mun Shin"' showing total 7 results
Start Over Author "Dong Mun Shin"
7 results on '"Dong Mun Shin"'

1. Uncovering potential causal genes for undiagnosed congenital anomalies using an in-house pipeline for trio-based whole-genome sequencing

Author

Jeong-Min Kim, Hye-Won Cho, Dong Mun Shin, Oc-Hee Kim, Jihyun Kim, Hyeji Lee, Gang-Hee Lee, Joon-Yong An, Misun Yang, Heui Seung Jo, Ja-Hyun Jang, Yun Sil Chang, Hyun-Young Park, and Mi-Hyun Park

Subjects
Congenital Anomalies, Whole Genome Sequencing, Genetic Variant, Rare Disease, Medicine, Genetics, QH426-470
Abstract

Abstract Background Congenital anomalies (CAs) encompass a wide spectrum of structural and functional abnormalities during fetal development, commonly presenting at birth. Identifying the cause of CA is essential for accurate diagnosis and treatment. Using a target-gene approach, genetic variants could be found in certain CA patients. However, some patients were genetically undiagnosed; therefore, it is imperative to identify the causative variants from whole genome sequence (WGS) data of these patients. Results An in-house pipeline utilizing DRAGEN-GATK-Hail was established for trio-based WGS data analysis (n = 18 undiagnosed CA patients and their parents) and thirty-five candidate variants, including SNV/Indel, CNV, and SV were identified. Among them, 10 variants of seven coding genes were selected as possible causal variants by variant pathogenicity, genotype–phenotype analysis, and a multidisciplinary team. Finally, functional validation of six genes including RYR3, NRXN1, FREM2, CSMD1, RARS1, and NOTCH1, revealed various phenotypes in zebrafish models that aligned with those observed in each patient. In addition to the above findings, eleven diagnostic variants initially discovered in a targeted-gene analysis from a previous study were also identified as diagnostic variants and the in-house pipeline demonstrated a significant advantage in accurately and efficiently identifying de novo variants (DNVs), compound heterozygous (CH), and homozygous variants. Conclusions Taken together, the in-house pipeline established in this study provides a highly valuable diagnostic tool for the identification of potential candidate variants in patients with CA. Further research into the molecular mechanisms related to the development of CAs could shed light on the functional aspects of these genetic variations and contribute to the development of therapeutic drugs.

Published
2025
Full Text
View/download PDF

2. The contribution of common and rare genetic variants to variation in metabolic traits in 288,137 East Asians

Author

Young Jin Kim, Sanghoon Moon, Mi Yeong Hwang, Sohee Han, Hye-Mi Jang, Jinhwa Kong, Dong Mun Shin, Kyungheon Yoon, Sung Min Kim, Jong-Eun Lee, Anubha Mahajan, Hyun-Young Park, Mark I. McCarthy, Yoon Shin Cho, and Bong-Jo Kim

Subjects
Science
Abstract

Metabolic traits are heritable intermediate phenotypes widely used in assessing the risk of various diseases. By conducting a genome-wide meta-analysis for metabolic traits in 288,137 East Asians, the authors highlight the interplay of common and rare variants on inherited risk of metabolic traits.

Published
2022
Full Text
View/download PDF

3. GEN2VCF: a converter for human genome imputation output format to VCF format

Author

Young-Jin Kim, Bong-Jo Kim, Mi Yeong Hwang, Dong Mun Shin, and Keun Ho Ryu

Subjects
0106 biological sciences, 0301 basic medicine, Genotype, Posterior probability, SNP, Biology, computer.software_genre, Polymorphism, Single Nucleotide, 01 natural sciences, Biochemistry, 03 medical and health sciences, Software, Genetics, Humans, Converter, Association mapping, Molecular Biology, Imputation, Parsing, Variant Call Format, Genotype imputation, Human genome, Genome, Human, business.industry, Genomics, 030104 developmental biology, Sample size determination, Data mining, business, computer, Algorithms, Imputation (genetics), Genome-Wide Association Study, Research Article, 010606 plant biology & botany, Test data
Abstract

Background For a genome-wide association study in humans, genotype imputation is an essential analysis tool for improving association mapping power. When IMPUTE software is used for imputation analysis, an imputation output (GEN format) should be converted to variant call format (VCF) with imputed genotype dosage for association analysis. However, the conversion requires multiple software packages in a pipeline with a large amount of processing time. Objective We developed GEN2VCF, a fast and convenient GEN format to VCF conversion tool with dosage support. Methods The performance of GEN2VCF was compared to BCFtools, QCTOOL, and Oncofunco. The test data set was a 1 Mb GEN-formatted file of 5000 samples. To determine the performance of various sample sizes, tests were performed from 1000 to 5000 samples with a step size of 1000. Runtime and memory usage were used as performance measures. Results GEN2VCF showed drastically increased performances with respect to runtime and memory usage. Runtime and memory usage of GEN2VCF was at least 1.4- and 7.4-fold lower compared to other methods, respectively. Conclusions GEN2VCF provides users with efficient conversion from GEN format to VCF with the best-guessed genotype, genotype posterior probabilities, and genotype dosage, as well as great flexibility in implementation with other software packages in a pipeline.

Published
2020
Full Text
View/download PDF

4. Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Author

Anubha Mahajan, Cassandra N Spracklen, Weihua Zhang, Maggie CY Ng, Lauren E Petty, Hidetoshi Kitajima, Grace Z Yu, Sina Rüeger, Leo Speidel, Young Jin Kim, Momoko Horikoshi, Josep M Mercader, Daniel Taliun, Sanghoon Moon, Soo-Heon Kwak, Neil R Robertson, Nigel W Rayner, Marie Loh, Bong-Jo Kim, Joshua Chiou, Irene Miguel-Escalada, Pietro della Briotta Parolo, Kuang Lin, Fiona Bragg, Michael H Preuss, Fumihiko Takeuchi, Jana Nano, Xiuqing Guo, Amel Lamri, Masahiro Nakatochi, Robert A Scott, Jung-Jin Lee, Alicia Huerta-Chagoya, Mariaelisa Graff, Jin-Fang Chai, Esteban J Parra, Jie Yao, Lawrence F Bielak, Yasuharu Tabara, Yang Hai, Valgerdur Steinthorsdottir, James P Cook, Mart Kals, Niels Grarup, Ellen M Schmidt, Ian Pan, Tamar Sofer, Matthias Wuttke, Chloe Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Meraj Ahmad, Raymond Noordam, Victor JY Lim, Claudia HT Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M Raffield, Cécile Lecoeur, Nisa M Maruthur, Bram Peter Prins, Aude Nicolas, Lisa R Yanek, Guanjie Chen, Richard A Jensen, Salman Tajuddin, Edmond Kabagambe, Ping An, Anny H Xiang, Hyeok Sun Choi, Brian E Cade, Jingyi Tan, Fernando Abaitua, Linda S Adair, Adebowale Adeyemo, Carlos A Aguilar-Salinas, Masato Akiyama, Sonia S Anand, Alain Bertoni, Zheng Bian, Jette Bork-Jensen, Ivan Brandslund, Jennifer A Brody, Chad M Brummett, Thomas A Buchanan, Mickaël Canouil, Juliana CN Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, Swapan K Das, H. Janaka de Silva, George Dedoussis, Latchezar Dimitrov, Ayo P Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S Emery, Daniel S Evans, Michele K Evans, Krista Fischer, James S Floyd, Ian Ford, Myriam Fornage, Oscar H Franco, Timothy M Frayling, Barry I Freedman, Christian Fuchsberger, Pauline Genter, Hertzel C Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Mark O Goodarzi, Penny Gordon-Larsen, David Gorkin, Myron Gross, Yu Guo, Sophie Hackinger, Sohee Han, Andrew T Hattersley, Christian Herder, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md. Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B Jonas, Marit E Jørgensen, Torben Jørgensen, Yoichiro Kamatani, Fouad R Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M Keaton, Abel N Kho, Chiea-Chuen Khor, Muhammad G Kibriya, Duk-Hwan Kim, Katsuhiko Kohara, Jennifer Kriebel, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A Lange, Myung-Shik Lee, Nanette R Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E Locke, Tin Louie, Jian’an Luan, Andrea O Luk, Xi Luo, Jun Lv, Valeriya Lyssenko, Vasiliki Mamakou, K Radha Mani, Thomas Meitinger, Andres Metspalu, Andrew D Morris, Girish N. Nadkarni, Jerry L Nadler, Michael A Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R Patel, Mark A Pereira, Annette Peters, Fraser J Pirie, Bianca Porneala, Gauri Prasad, Sebastian Preissl, Laura J Rasmussen-Torvik, Alexander P Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Maike Sander, Kevin Sandow, Naveed Sattar, Sebastian Schönherr, Claudia Schurmann, Mohammad Shahriar, Jinxiu Shi, Dong Mun Shin, Daniel Shriner, Jennifer A Smith, Wing Yee So, Alena Stančáková, Adrienne M Stilp, Konstantin Strauch, Ken Suzuki, Atsushi Takahashi, Kent D Taylor, Barbara Thorand, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Brian Tomlinson, Jason M Torres, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S Udler, Adan Valladares-Salgado, Rob M van Dam, Jan B van Klinken, Rohit Varma, Marijana Vujkovic, Niels Wacher-Rodarte, Ellie Wheeler, Eric A Whitsel, Ananda R Wickremasinghe, Konstantin Willems van Dijk, Daniel R Witte, Chittaranjan S Yajnik, Ken Yamamoto, Toshimasa Yamauchi, Loïc Yengo, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Liang Zhang, Wei Zheng, null FinnGen, Leslie J Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A Province, Craig L Hanis, Patricia A Peyser, Erik Ingelsson, Alan B Zonderman, Bruce M Psaty, Ya-Xing Wang, Charles N Rotimi, Diane M Becker, Fumihiko Matsuda, Yongmei Liu, Eleftheria Zeggini, Mitsuhiro Yokota, Stephen S Rich, Charles Kooperberg, James S Pankow, James C Engert, Yii-Der Ida Chen, Philippe Froguel, James G Wilson, Wayne HH Sheu, Sharon LR Kardia, Jer-Yuarn Wu, M Geoffrey Hayes, Ronald CW Ma, Tien-Yin Wong, Leif Groop, Dennis O Mook-Kanamori, Giriraj R Chandak, Francis S Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M Sale, Habibul Ahsan, Ayesha A Motala, Xiao-Ou Shu, Kyong-Soo Park, J Wouter Jukema, Miguel Cruz, Roberta McKean-Cowdin, Harald Grallert, Ching-Yu Cheng, Erwin P Bottinger, Abbas Dehghan, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Colin NA Palmer, Simin Liu, Goncalo Abecasis, Jaspal S Kooner, Ruth JF Loos, Kari E North, Christopher A Haiman, Jose C Florez, Danish Saleheen, Torben Hansen, Oluf Pedersen, Reedik Mägi, Claudia Langenberg, Nicholas J Wareham, Shiro Maeda, Takashi Kadowaki, Juyoung Lee, Iona Y Millwood, Robin G Walters, Kari Stefansson, Simon R Myers, Jorge Ferrer, Kyle J Gaulton, James B Meigs, Karen L Mohlke, Anna L Gloyn, Donald W Bowden, Jennifer E Below, John C Chambers, Xueling Sim, Michael Boehnke, Jerome I Rotter, Mark I McCarthy, and Andrew P Morris

Subjects
0303 health sciences, Transferability, Translation (biology), Type 2 diabetes, Biology, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Evolutionary biology, Global health, medicine, Genetic risk, Gene, 030217 neurology & neurosurgery, 030304 developmental biology, Genetic association
Abstract

We assembled an ancestrally diverse collection of genome-wide association studies of type 2 diabetes (T2D) in 180,834 cases and 1,159,055 controls (48.9% non-European descent). We identified 277 loci at genome-wide significance (p-8), including 237 attaining a more stringent trans-ancestry threshold (p-9), which were delineated to 338 distinct association signals. Trans-ancestry meta-regression offered substantial enhancements to fine-mapping, with 58.6% of associations more precisely localised due to population diversity, and 54.4% of signals resolved to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying foundations for functional investigations. Trans-ancestry genetic risk scores enhanced transferability across diverse populations, providing a step towards more effective clinical translation to improve global health.

Published
2020
Full Text
View/download PDF

5. Identification of type 2 diabetes loci in 433,540 East Asian individuals

Author

Chien-Hsiun Chen, Anna L. Gloyn, Atsushi Takahashi, Sohee Han, Ken Suzuki, Mark A Pereira, Shi Jinxiu, Fiona Bragg, Yii-Der Ida Chen, Robin G. Walters, Takashi Kadowaki, Charumathi Sabanayagam, Annie-Green Howard, Mark I. McCarthy, Zheng Bian, Zhengming Chen, E-Shyong Tai, Chii-Min Hwu, Cassandra N. Spracklen, Yuan-Tsong Chen, Linda S. Adair, Momoko Horikoshi, Guozhi Jiang, Ching-Yu Cheng, Mi Yeong Hwang, Andrew P. Morris, Karen L. Mohlke, John C. Chambers, Jian-Min Yuan, Woon-Puay Koh, Hyeok Sun Choi, Ju Young Lee, Bong-Jo Kim, Masato Akiyama, Sahoko Ichihara, Xueling Sim, Norihiro Kato, Kuang Lin, Jirong Long, Xiuqing Guo, Fumihiko Takeuchi, Penny Gordon-Larsen, Hannah J Perrin, Young Jin Kim, Lee-Ming Chuang, Weihua Zhang, Rob M. van Dam, Andrea O.Y. Luk, Masahiro Nakatochi, Yukinori Okada, Katsuhiko Kohara, Yoichiro Kamatani, Jerome I. Rotter, Iona Y Millwood, Jer-Yuarn Wu, Canqing Yu, Wayne Huey-Herng Sheu, Shiro Maeda, Jost B. Jonas, Yasuharu Tabara, Mitsuhiro Yokota, Li-Ching Chang, Toshimasa Yamauchi, Shufa Du, Yu Guo, Yoon Shin Cho, Yi-Jen Hung, Jie Yao, Soo Heon Kwak, Hye-Mi Jang, Maggie C.Y. Ng, Xiao-Ou Shu, Myung-Shik Lee, Kyungheon Yoon, Sarah M Brotman, Sanghoon Moon, Tien Yin Wong, Martijn van de Bunt, Michiya Igase, Claudia H. T. Tam, Fumihiko Matsuda, Wei Zheng, Liang Zhang, Yong-Bing Xiang, Victor Jun Yu Lim, Ronald Cw Ma, Liming Li, Tomohiro Katsuya, Jianjun Liu, Jun Lv, Jennifer E. Below, Anubha Mahajan, Kyong-Soo Park, Masato Isono, Wing-Yee So, Nanette R. Lee, Brian Tomlinson, Juliana C.N. Chan, Lauren E. Petty, Chiea Chuen Khor, Miao-Li Chee, Ken Yamamoto, Wei Huang, Michael Boehnke, Jin-Fang Chai, Donald W. Bowden, Apoorva K Iyengar, Dong Mun Shin, Myron D. Gross, Takahisa Kawaguchi, Ya Xing Wang, and Fuu Jen Tsai

Subjects
Ankyrins, Male, 0301 basic medicine, Transcription, Genetic, endocrine system diseases, Nerve Tissue Proteins, 030209 endocrinology & metabolism, Locus (genetics), Genome-wide association study, Type 2 diabetes, Biology, Article, Body Mass Index, 03 medical and health sciences, 0302 clinical medicine, Asian People, ANK1, medicine, Humans, Genetic Predisposition to Disease, RNA, Messenger, Allele, Eye Proteins, Gene, Alleles, 030304 developmental biology, ALDH2, Genetic association, 2. Zero hunger, Homeodomain Proteins, Genetics, 0303 health sciences, Multidisciplinary, Asia, Eastern, Aldehyde Dehydrogenase, Mitochondrial, Case-control study, nutritional and metabolic diseases, medicine.disease, Europe, 030104 developmental biology, Diabetes Mellitus, Type 2, Case-Control Studies, Meta-analysis, Expression quantitative trait loci, Female, Body mass index, 030217 neurology & neurosurgery, Genome-Wide Association Study, Transcription Factors
Abstract

SUMMARYMeta-analyses of genome-wide association studies (GWAS) have identified >240 loci associated with type 2 diabetes (T2D), however most loci have been identified in analyses of European-ancestry individuals. To examine T2D risk in East Asian individuals, we meta-analyzed GWAS data in 77,418 cases and 356,122 controls. In the main analysis, we identified 298 distinct association signals at 178 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 56 loci newly implicated in T2D predisposition. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. New associations include signals in/near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect muscle and adipose differentiation. At another locus, eQTLs at two overlapping T2D signals act through two genes, NKX6-3 and ANK1, in different tissues. Association studies in diverse populations identify additional loci and elucidate disease genes, biology, and pathways.Type 2 diabetes (T2D) is a common metabolic disease primarily caused by insufficient insulin production and/or secretion by the pancreatic β cells and insulin resistance in peripheral tissues1. Most genetic loci associated with T2D have been identified in populations of European (EUR) ancestry, including a recent meta-analysis of genome-wide association studies (GWAS) of nearly 900,000 individuals of European ancestry that identified >240 loci influencing the risk of T2D2. Differences in allele frequency between ancestries affect the power to detect associations within a population, particularly among variants rare or monomorphic in one population but more frequent in another3,4. Although smaller than studies in European populations, a recent T2D meta-analysis in almost 200,000 Japanese individuals identified 28 additional loci4. The relative contributions of different pathways to the pathophysiology of T2D may also differ between ancestry groups. For example, in East Asian (EAS) populations, T2D prevalence is greater than in European populations among people of similar body mass index (BMI) or waist circumference5. We performed the largest meta-analysis of East Asian individuals to identify new genetic associations and provide insight into T2D pathogenesis.

Published
2019
Full Text
View/download PDF

6. The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits

Author

Kyungheon Yoon, Yun Kyoung Kim, Young-Jin Kim, Min Young Park, Jae Kyung Park, Yontao Lu, Bong-Jo Kim, Sohee Han, Daesub Song, Sanghoon Moon, Dong Mun Shin, Mi Yeong Hwang, Taejoon Park, Hye-Mi Jang, and Jong Eun Lee

Subjects
0301 basic medicine, Adult, Genotype, Sequencing data, Mutation, Missense, lcsh:Medicine, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, 03 medical and health sciences, 0302 clinical medicine, Republic of Korea, Missense mutation, Humans, Alanine aminotransferase, lcsh:Science, ALDH2, Aged, Biological Specimen Banks, Genetics, Multidisciplinary, Korean population, Genome, Human, lcsh:R, Genetic Variation, Reproducibility of Results, Middle Aged, Biobank, 030104 developmental biology, Blood, Genetic Loci, lcsh:Q, 030217 neurology & neurosurgery, Imputation (genetics), Genome-Wide Association Study
Abstract

We introduce the design and implementation of a new array, the Korea Biobank Array (referred to as KoreanChip), optimized for the Korean population and demonstrate findings from GWAS of blood biochemical traits. KoreanChip comprised >833,000 markers including >247,000 rare-frequency or functional variants estimated from >2,500 sequencing data in Koreans. Of the 833 K markers, 208 K functional markers were directly genotyped. Particularly, >89 K markers were presented in East Asians. KoreanChip achieved higher imputation performance owing to the excellent genomic coverage of 95.38% for common and 73.65% for low-frequency variants. From GWAS (Genome-wide association study) using 6,949 individuals, 28 associations were successfully recapitulated. Moreover, 9 missense variants were newly identified, of which we identified new associations between a common population-specific missense variant, rs671 (p.Glu457Lys) of ALDH2, and two traits including aspartate aminotransferase (P = 5.20 × 10−13) and alanine aminotransferase (P = 4.98 × 10−8). Furthermore, two novel missense variants of GPT with rare frequency in East Asians but extreme rarity in other populations were associated with alanine aminotransferase (rs200088103; p.Arg133Trp, P = 2.02 × 10−9 and rs748547625; p.Arg143Cys, P = 1.41 × 10−6). These variants were successfully replicated in 6,000 individuals (P = 5.30 × 10−8 and P = 1.24 × 10−6). GWAS results suggest the promising utility of KoreanChip with a substantial number of damaging variants to identify new population-specific disease-associated rare/functional variants.

Published
2019

7. Replication of Previously Type 2 Diabetes Associated Loci in 35,000 Samples of Korean Population

Author

Young-Jin Kim, Mi Yeong Hwang, and Dong Mun Shin

Subjects
Genetics, endocrine system diseases, SLC30A8, Endocrinology, Diabetes and Metabolism, nutritional and metabolic diseases, Genome-wide association study, Type 2 diabetes, Biology, medicine.disease, Obesity, Genome, Genotype, Internal Medicine, medicine, biology.protein, CDKAL1, Genetic association
Abstract

In the last decade, genome-wide association studies (GWAS) have revealed about hundreds of loci associated with type 2 diabetes(T2D) and related traits. However, most of loci have been discovered based on Europeans and a few GWAS conducted in populations with East Asian ancestry. To identify genetic variants responsible for complex traits such as T2D, obesity, and blood biochemical traits in Koreans, Korea Biobank Array(KBA) project was initiated in 2014. KBA is designed to contain about 830K tagging and functional variants optimized for Korean genome. In this study, quality controlled genotype data of about 35,000 samples was used. Among them, we conducted genome-wide association scan in 3,022 T2D case subjects and 27,195 control subjects. As a result, we replicated five previously known loci (CDKAL1, SLC30A8, CDKN2A, KCNQ1, and HNF1B) at genome-wide significance (P Disclosure Y. Kim: None. M. Hwang: None. D. Shin: None.

Published
2018
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results