96 results on '"SANGHOON MOON"'
Search Results
2. Programmable Nuclease-Based Integration into Novel Extragenic Genomic Safe Harbor Identified from Korean Population-Based CNV Analysis
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Eun-Seo Lee, Sanghoon Moon, Kwaku Dad Abu-Bonsrah, Yun Kyoung Kim, Mi Yeong Hwang, Young Jin Kim, Seokjoong Kim, Nathaniel S. Hwang, Hyongbum Henry Kim, and Bong-Jo Kim
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Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Here, we found two genomic safe harbor (GSH) candidates from chromosomes 3 and 8, based on large-scale population-based cohort data from 4,694 Koreans by CNV analysis. Furthermore, estimated genotype of these CNVRs was validated by quantitative real-time PCR, and epidemiological data examined no significant genetic association between diseases or traits and two CNVRs. After screening the GSH candidates by in silico approaches, we designed TALEN pairs to integrate EGFP expression cassette into human cell lines in order to confirm the functionality of GSH candidates in an in vitro setting. As a result, transgene insertion into one of the two loci using TALEN showed robust transgene expression comparable to that with an AAVS1 site without significantly perturbing neighboring genes. Changing the promoter or cell type did not noticeably disturb this trend. Thus, we could validate two CNVRs as a site for effective and safe transgene insertion in human cells. Keywords: genome editing, TALEN, safe harbor, copy number variation region
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- 2019
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3. Interethnic analyses of blood pressure loci in populations of East Asian and European descent
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Fumihiko Takeuchi, Masato Akiyama, Nana Matoba, Tomohiro Katsuya, Masahiro Nakatochi, Yasuharu Tabara, Akira Narita, Woei-Yuh Saw, Sanghoon Moon, Cassandra N. Spracklen, Jin-Fang Chai, Young-Jin Kim, Liang Zhang, Chaolong Wang, Huaixing Li, Honglan Li, Jer-Yuarn Wu, Rajkumar Dorajoo, Jovia L. Nierenberg, Ya Xing Wang, Jing He, Derrick A. Bennett, Atsushi Takahashi, Yukihide Momozawa, Makoto Hirata, Koichi Matsuda, Hiromi Rakugi, Eitaro Nakashima, Masato Isono, Matsuyuki Shirota, Atsushi Hozawa, Sahoko Ichihara, Tatsuaki Matsubara, Ken Yamamoto, Katsuhiko Kohara, Michiya Igase, Sohee Han, Penny Gordon-Larsen, Wei Huang, Nanette R. Lee, Linda S. Adair, Mi Yeong Hwang, Juyoung Lee, Miao Li Chee, Charumathi Sabanayagam, Wanting Zhao, Jianjun Liu, Dermot F. Reilly, Liang Sun, Shaofeng Huo, Todd L. Edwards, Jirong Long, Li-Ching Chang, Chien-Hsiun Chen, Jian-Min Yuan, Woon-Puay Koh, Yechiel Friedlander, Tanika N. Kelly, Wen Bin Wei, Liang Xu, Hui Cai, Yong-Bing Xiang, Kuang Lin, Robert Clarke, Robin G. Walters, Iona Y. Millwood, Liming Li, John C. Chambers, Jaspal S. Kooner, Paul Elliott, Pim van der Harst, The International Genomics of Blood Pressure (iGEN-BP) Consortium, Zhengming Chen, Makoto Sasaki, Xiao-Ou Shu, Jost B. Jonas, Jiang He, Chew-Kiat Heng, Yuan-Tsong Chen, Wei Zheng, Xu Lin, Yik-Ying Teo, E-Shyong Tai, Ching-Yu Cheng, Tien Yin Wong, Xueling Sim, Karen L. Mohlke, Masayuki Yamamoto, Bong-Jo Kim, Tetsuro Miki, Toru Nabika, Mitsuhiro Yokota, Yoichiro Kamatani, Michiaki Kubo, and Norihiro Kato
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Science - Abstract
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.
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- 2018
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4. Multiple genotype–phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population
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Sanghoon Moon, Young Lee, Sungho Won, and Juyoung Lee
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Multiple variants ,Multiple traits ,Metabolic syndrome ,11q23.3 ,SIDT2 ,Medicine ,Genetics ,QH426-470 - Abstract
Abstract Background Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these variants, we conducted a multiple-genotype and multiple-phenotype genome-wide association analysis using the family-based quasi-likelihood score (MFQLS) test. For this analysis, we used 7211 and 2838 genotyped study subjects for discovery and replication, respectively. We also performed a multiple-genotype and multiple-phenotype analysis of a gene-based single-nucleotide polymorphism (SNP) set. Results We found an association between metabolic syndrome and an intronic SNP pair, rs7107152 and rs1242229, in SIDT2 gene at 11q23.3. Both SNPs correlate with the expression of SIDT2 and TAGLN, whose products promote insulin secretion and lipid metabolism, respectively. This SNP pair showed statistical significance at the replication stage. Conclusions Our findings provide insight into an underlying mechanism that contributes to metabolic syndrome.
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- 2018
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5. Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: results from the Korea Epigenome Study (KES)
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Song Cheol Kim, Song Lee, In-Uk Koh, Nak-Hyeon Choi, Kibaick Lee, Ho-Yeong Yu, Jun Ho Yun, Jin-Hwa Kong, and Sanghoon Moon
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Diseases of the endocrine glands. Clinical endocrinology ,RC648-665 - Abstract
Introduction Obesity is growing global health concern and highly associated with increased risk of metabolic diseases including type 2 diabetes. We aimed to discover new differential DNA methylation patterns predisposing obesity and prioritize surrogate epigenetic markers in Koreans.Research design and methods We performed multistage epigenome-wide analyses to identify differentially expressed CpGs in obesity using the Illumina HumanMethylationEPIC array (EPIC). Forty-eight CpGs showed significant differences across three phases: 902 whole blood DNAs from two cohorts (phase 1: n=450, phase 2: n=377) and a hospital-based sample (phase 3: n=75). Samples from phase III participants were used to examine whether the 48 CpGs are significant in the fat tissue and influenced gene expression. Furthermore, we investigated the epigenetic effect of CpG loci in childhood obesity (n=94).Results Seven of the 48 CpGs exhibited similar changes in the fat tissue along with gene expression changes. In particular, hypomethylated CpG (cg13424229) on the GATA1 transcription factor cluster of CPA3 promoter was related to its increased gene expression and showed consistent effect in childhood obesity. Interestingly, subsequent analysis using RNA sequencing data from 21 preadipocytes and 26 adipocytes suggested CPA3 as a potential obesity-related gene. Moreover, expression patterns from RNA sequencing and public Gene Expression Omnibus showed the correlation between CPA3 and type 2 diabetes (T2D) and asthma.Conclusions Our finding prioritizes influential genes in obesity and provides new evidence for the role of CPA3 linking obesity, T2D, and asthma.
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- 2020
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6. On the association analysis of CNV data: a fast and robust family-based association method
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Meiling Liu, Sanghoon Moon, Longfei Wang, Sulgi Kim, Yeon-Jung Kim, Mi Yeong Hwang, Young Jin Kim, Robert C. Elston, Bong-Jo Kim, and Sungho Won
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CNV ,Association analysis ,Score test ,Hematocrit ,Computer applications to medicine. Medical informatics ,R858-859.7 ,Biology (General) ,QH301-705.5 - Abstract
Abstract Background Copy number variation (CNV) is known to play an important role in the genetics of complex diseases and several methods have been proposed to detect association of CNV with phenotypes of interest. Statistical methods for CNV association analysis can be categorized into two different strategies. First, the copy number is estimated by maximum likelihood and association of the expected copy number with the phenotype is tested. Second, the observed probe intensity measurements can be directly used to detect association of CNV with the phenotypes of interest. Results For each strategy we provide a statistic that can be applied to extended families. The computational efficiency of the proposed methods enables genome-wide association analysis and we show with simulation studies that the proposed methods outperform other existing approaches. In particular, we found that the first strategy is always more efficient than the second strategy no matter whether copy numbers for each individual are well identified or not. With the proposed methods, we performed genome-wide CNV association analyses of hematological trait, hematocrit, on 521 Korean family samples. Conclusions We found that statistical analysis with the expected copy number is more powerful than the statistic with the probe intensity measurements regardless of the accuracy of the estimation of copy numbers.
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- 2017
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7. Identification of a Copy Number Variation on Chromosome 20q13.12 Associated with Osteoporotic Fractures in the Korean Population
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Tae-Joon Park, Mi Yeong Hwang, Sanghoon Moon, Joo-Yeon Hwang, Min Jin Go, and Bong-Jo Kim
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DNA copy number variations ,genome-wide association study ,osteoporotic fracture ,real-time polymerase chain reaction ,Genetics ,QH426-470 - Abstract
Osteoporotic fractures (OFs) are critical hard outcomes of osteoporosis and are characterized by decreased bone strength induced by low bone density and microarchitectural deterioration in bone tissue. Most OFs cause acute pain, hospitalization, immobilization, and slow recovery in patients and are associated with increased mortality. A variety of genetic studies have suggested associations of genetic variants with the risk of OF. Genome-wide association studies have reported various single-nucleotide polymorphisms and copy number variations (CNVs) in European and Asian populations. To identify CNV regions associated with OF risk, we conducted a genome-wide CNV study in a Korean population. We performed logistic regression analyses in 1,537 Korean subjects (299 OF cases and 1,238 healthy controls) and identified a total of 8 CNV regions significantly associated with OF (p < 0.05). Then, one CNV region located on chromosome 20q13.12 was selected for experimental validation. The selected CNV region was experimentally validated by quantitative polymerase chain reaction. The CNV region of chromosome 20q13.12 is positioned upstream of a family of long non-coding RNAs, LINC01260. Our findings could provide new information on the genetic factors associated with the risk of OF.
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- 2016
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8. Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes
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Minako Imamura, Atsushi Takahashi, Toshimasa Yamauchi, Kazuo Hara, Kazuki Yasuda, Niels Grarup, Wei Zhao, Xu Wang, Alicia Huerta-Chagoya, Cheng Hu, Sanghoon Moon, Jirong Long, Soo Heon Kwak, Asif Rasheed, Richa Saxena, Ronald C. W. Ma, Yukinori Okada, Minoru Iwata, Jun Hosoe, Nobuhiro Shojima, Minaka Iwasaki, Hayato Fujita, Ken Suzuki, John Danesh, Torben Jørgensen, Marit E. Jørgensen, Daniel R. Witte, Ivan Brandslund, Cramer Christensen, Torben Hansen, Josep M. Mercader, Jason Flannick, Hortensia Moreno-Macías, Noël P. Burtt, Rong Zhang, Young Jin Kim, Wei Zheng, Jai Rup Singh, Claudia H. T. Tam, Hiroshi Hirose, Hiroshi Maegawa, Chikako Ito, Kohei Kaku, Hirotaka Watada, Yasushi Tanaka, Kazuyuki Tobe, Ryuzo Kawamori, Michiaki Kubo, Yoon Shin Cho, Juliana C. N. Chan, Dharambir Sanghera, Philippe Frossard, Kyong Soo Park, Xiao-Ou Shu, Bong-Jo Kim, Jose C. Florez, Teresa Tusié-Luna, Weiping Jia, E Shyong Tai, Oluf Pedersen, Danish Saleheen, Shiro Maeda, and Takashi Kadowaki
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Science - Abstract
Here, Imamuraet al. conduct meta-analysis of genome-wide association studies to identify novel susceptibility loci for type 2 diabetes (T2D) in the Japanese population. By doing so, this study shows that both ethnicity-specific and ethnically-shared genetic loci can contribute to T2D risk.
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- 2016
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9. Integrated Analysis of Tissue-Specific Promoter Methylation and Gene Expression Profile in Complex Diseases
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Kibaick Lee, Sanghoon Moon, Mi-Jin Park, In-Uk Koh, Nak-Hyeon Choi, Ho-Yeong Yu, Young Jin Kim, Jinhwa Kong, Hee Gyung Kang, Song Cheol Kim, and Bong-Jo Kim
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tissue-specific expression ,DNA methylation ,type 2 diabetes ,obesity ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
This study investigated whether the promoter region of DNA methylation positively or negatively regulates tissue-specific genes (TSGs) and if it correlates with disease pathophysiology. We assessed tissue specificity metrics in five human tissues, using sequencing-based approaches, including 52 whole genome bisulfite sequencing (WGBS), 52 RNA-seq, and 144 chromatin immunoprecipitation sequencing (ChIP-seq) data. A correlation analysis was performed between the gene expression and DNA methylation levels of the TSG promoter region. The TSG enrichment analyses were conducted in the gene–disease association network (DisGeNET). The epigenomic association analyses of CpGs in enriched TSG promoters were performed using 1986 Infinium MethylationEPIC array data. A correlation analysis showed significant associations between the promoter methylation and 449 TSGs’ expression. A disease enrichment analysis showed that diabetes- and obesity-related diseases were high-ranked. In an epigenomic association analysis based on obesity, 62 CpGs showed statistical significance. Among them, three obesity-related CpGs were newly identified and replicated with statistical significance in independent data. In particular, a CpG (cg17075888 of PDK4), considered as potential therapeutic targets, were associated with complex diseases, including obesity and type 2 diabetes. The methylation changes in a substantial number of the TSG promoters showed a significant association with metabolic diseases. Collectively, our findings provided strong evidence of the relationship between tissue-specific patterns of epigenetic changes and metabolic diseases.
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- 2020
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10. Genome-Wide Association Study Identifies Candidate Loci Associated with Platelet Count in Koreans
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Ji Hee Oh, Yun Kyoung Kim, Sanghoon Moon, Young Jin Kim, and Bong-Jo Kim
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genome-wide association study ,Korea ,platelet count ,Genetics ,QH426-470 - Abstract
Platelets are derived from the fragments that are formed from the cytoplasm of bone marrow megakaryocytes-small irregularly shaped anuclear cells. Platelets respond to vascular damage, contracts blood vessels, and attaches to the damaged region, thereby stopping bleeding, together with the action of blood coagulation factors. Platelet activation is known to affect genes associated with vascular risk factors, as well as with arteriosclerosis and myocardial infarction. Here, we performed a genome-wide association study with 352,228 single-nucleotide polymorphisms typed in 8,842 subjects of the Korea Association Resource (KARE) project and replicated the results in 7,861 subjects from an independent population. We identified genetic associations between platelet count and common variants nearby chromosome 4p16.1 (p = 1.46 × 10-10, in the KIAA0232 gene), 6p21 (p = 1.36 × 10-7, in the BAK1 gene), and 12q24.12 (p = 1.11 × 10-15, in the SH2B3 gene). Our results illustrate the value of large-scale discovery and a focus for several novel research avenues.
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- 2014
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11. Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populations: A transethnic genome-wide meta-analysis.
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Eleanor Wheeler, Aaron Leong, Ching-Ti Liu, Marie-France Hivert, Rona J Strawbridge, Clara Podmore, Man Li, Jie Yao, Xueling Sim, Jaeyoung Hong, Audrey Y Chu, Weihua Zhang, Xu Wang, Peng Chen, Nisa M Maruthur, Bianca C Porneala, Stephen J Sharp, Yucheng Jia, Edmond K Kabagambe, Li-Ching Chang, Wei-Min Chen, Cathy E Elks, Daniel S Evans, Qiao Fan, Franco Giulianini, Min Jin Go, Jouke-Jan Hottenga, Yao Hu, Anne U Jackson, Stavroula Kanoni, Young Jin Kim, Marcus E Kleber, Claes Ladenvall, Cecile Lecoeur, Sing-Hui Lim, Yingchang Lu, Anubha Mahajan, Carola Marzi, Mike A Nalls, Pau Navarro, Ilja M Nolte, Lynda M Rose, Denis V Rybin, Serena Sanna, Yuan Shi, Daniel O Stram, Fumihiko Takeuchi, Shu Pei Tan, Peter J van der Most, Jana V Van Vliet-Ostaptchouk, Andrew Wong, Loic Yengo, Wanting Zhao, Anuj Goel, Maria Teresa Martinez Larrad, Dörte Radke, Perttu Salo, Toshiko Tanaka, Erik P A van Iperen, Goncalo Abecasis, Saima Afaq, Behrooz Z Alizadeh, Alain G Bertoni, Amelie Bonnefond, Yvonne Böttcher, Erwin P Bottinger, Harry Campbell, Olga D Carlson, Chien-Hsiun Chen, Yoon Shin Cho, W Timothy Garvey, Christian Gieger, Mark O Goodarzi, Harald Grallert, Anders Hamsten, Catharina A Hartman, Christian Herder, Chao Agnes Hsiung, Jie Huang, Michiya Igase, Masato Isono, Tomohiro Katsuya, Chiea-Chuen Khor, Wieland Kiess, Katsuhiko Kohara, Peter Kovacs, Juyoung Lee, Wen-Jane Lee, Benjamin Lehne, Huaixing Li, Jianjun Liu, Stephane Lobbens, Jian'an Luan, Valeriya Lyssenko, Thomas Meitinger, Tetsuro Miki, Iva Miljkovic, Sanghoon Moon, Antonella Mulas, Gabriele Müller, Martina Müller-Nurasyid, Ramaiah Nagaraja, Matthias Nauck, James S Pankow, Ozren Polasek, Inga Prokopenko, Paula S Ramos, Laura Rasmussen-Torvik, Wolfgang Rathmann, Stephen S Rich, Neil R Robertson, Michael Roden, Ronan Roussel, Igor Rudan, Robert A Scott, William R Scott, Bengt Sennblad, David S Siscovick, Konstantin Strauch, Liang Sun, Morris Swertz, Salman M Tajuddin, Kent D Taylor, Yik-Ying Teo, Yih Chung Tham, Anke Tönjes, Nicholas J Wareham, Gonneke Willemsen, Tom Wilsgaard, Aroon D Hingorani, EPIC-CVD Consortium, EPIC-InterAct Consortium, Lifelines Cohort Study, Josephine Egan, Luigi Ferrucci, G Kees Hovingh, Antti Jula, Mika Kivimaki, Meena Kumari, Inger Njølstad, Colin N A Palmer, Manuel Serrano Ríos, Michael Stumvoll, Hugh Watkins, Tin Aung, Matthias Blüher, Michael Boehnke, Dorret I Boomsma, Stefan R Bornstein, John C Chambers, Daniel I Chasman, Yii-Der Ida Chen, Yduan-Tsong Chen, Ching-Yu Cheng, Francesco Cucca, Eco J C de Geus, Panos Deloukas, Michele K Evans, Myriam Fornage, Yechiel Friedlander, Philippe Froguel, Leif Groop, Myron D Gross, Tamara B Harris, Caroline Hayward, Chew-Kiat Heng, Erik Ingelsson, Norihiro Kato, Bong-Jo Kim, Woon-Puay Koh, Jaspal S Kooner, Antje Körner, Diana Kuh, Johanna Kuusisto, Markku Laakso, Xu Lin, Yongmei Liu, Ruth J F Loos, Patrik K E Magnusson, Winfried März, Mark I McCarthy, Albertine J Oldehinkel, Ken K Ong, Nancy L Pedersen, Mark A Pereira, Annette Peters, Paul M Ridker, Charumathi Sabanayagam, Michele Sale, Danish Saleheen, Juha Saltevo, Peter Eh Schwarz, Wayne H H Sheu, Harold Snieder, Timothy D Spector, Yasuharu Tabara, Jaakko Tuomilehto, Rob M van Dam, James G Wilson, James F Wilson, Bruce H R Wolffenbuttel, Tien Yin Wong, Jer-Yuarn Wu, Jian-Min Yuan, Alan B Zonderman, Nicole Soranzo, Xiuqing Guo, David J Roberts, Jose C Florez, Robert Sladek, Josée Dupuis, Andrew P Morris, E-Shyong Tai, Elizabeth Selvin, Jerome I Rotter, Claudia Langenberg, Inês Barroso, and James B Meigs
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Medicine - Abstract
BackgroundGlycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes.Methods & findingsUsing genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 × 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI 0.55-0.74) of African American adults with T2D to remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants.ConclusionsAs G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses.
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- 2017
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12. Practical Calling Approach for Exome Array-Based Genome-Wide Association Studies in Korean Population
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Tae-Joon Park, Lyong Heo, Sanghoon Moon, Young Jin Kim, Ji Hee Oh, Sohee Han, and Bong-Jo Kim
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Genetics ,QH426-470 - Abstract
Exome-based genotyping arrays are cost-effective and have recently been used as alternative platforms to whole-exome sequencing. However, the automated clustering algorithm in an exome array has a genotype calling problem in accuracy for identifying rare and low-frequency variants. To address these shortcomings, we present a practical approach for accurate genotype calling using the Illumina Infinium HumanExome BeadChip. We present comparison results and a statistical summary of our genotype data sets. Our data set comprises 14,647 Korean samples. To solve the limitation of automated clustering, we performed manual genotype clustering for the targeted identification of 46,076 variants that were identified using GenomeStudio software. To evaluate the effects of applying custom cluster files, we tested cluster files using 804 independent Korean samples and the same platform. Our study firstly suggests practical guidelines for exome chip quality control in Asian populations and provides valuable insight into an association study using exome chip.
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- 2015
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13. Unraveling the Genomic Architecture of the CYP3A Locus and ADME Genes for Personalized Tacrolimus Dosing
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Sang Il Min, Sanghoon Moon, Jae Berm Park, In-Jin Jang, Hyo Kee Kim, Ho Sik Shin, Seung Hwan Song, Sungkyoung Choi, Young-Jin Kim, Jihoon G. Yoon, Yuri Cho, Myoung Soo Kim, Min Goo Lee, Hye Eun Yoon, Bong-Jo Kim, Jaeseong Oh, Jongwon Ha, Jaeseok Yang, and Chul Woo Yang
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Adult ,Graft Rejection ,Male ,Oncology ,medicine.medical_specialty ,Adolescent ,Pharmacogenomic Variants ,Clinical Decision-Making ,Locus (genetics) ,Genome-wide association study ,Risk Assessment ,Tacrolimus ,Young Adult ,Pharmacokinetics ,Predictive Value of Tests ,Risk Factors ,Internal medicine ,Republic of Korea ,medicine ,Cytochrome P-450 CYP3A ,Humans ,Precision Medicine ,CYP3A5 ,Aged ,Retrospective Studies ,ADME ,Aged, 80 and over ,Transplantation ,business.industry ,Graft Survival ,Haplotype ,Confounding ,Middle Aged ,Kidney Transplantation ,Pharmacogenomic Testing ,Cross-Sectional Studies ,Treatment Outcome ,Haplotypes ,Pharmacogenetics ,Female ,business ,Immunosuppressive Agents ,Genome-Wide Association Study - Abstract
Background Tacrolimus (TAC) is an immunosuppressant widely prescribed following an allogenic organ transplant. Due to wide interindividual pharmacokinetic (PK) variability, optimizing TAC dosing based on genetic factors is required to minimize nephrotoxicity and acute rejections. Methods We enrolled 1133 participants receiving TAC from 4 cohorts, consisting of 3 with kidney transplant recipients and 1 with healthy males from clinical trials. The effects of clinical factors were estimated to appropriately control confounding variables. A genome-wide association study (GWAS), haplotype analysis, and a gene-based association test were conducted using the Korea Biobank Array or targeted sequencing for 114 pharmacogenes. Results GWAS verified that CYP3A5*3 is the only common variant associated with TAC PK variability in Koreans. We detected several CYP3A5 and CYP3A4 rare variants which could potentially affect TAC metabolism. The haplotype structure of CYP3A5 stratified by CYP3A5*3 was a significant factor for CYP3A5 rare variant interpretation. CYP3A4 rare variant carriers among CYP3A5 intermediate metabolizers displayed higher TAC trough levels. Gene-based association tests in the 61 absorption, distribution, metabolism, and excretion (ADME) genes revealed that CYP1A1 are associated with additional TAC PK variability: CYP1A1 rare variant carriers among CYP3A5 poor metabolizers showed lower TAC trough levels than the noncarrier controls. Conclusions Our study demonstrates that rare variant profiling of CYP3A5 and CYP3A4, combined with the haplotype structures of CYP3A locus, provide additive value for personalized TAC dosing. We also identified a novel association between CYP1A1 rare variants and TAC PK variability in the CYP3A5 nonexpressers which needs to be further investigated.Supplemental Visual Abstract; http://links.lww.com/TP/C134.
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- 2021
14. BioSMACK: A linux Live CD for analysis of genome-wide association.
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Chang Bum Hong, Young Jin Kim, Sanghoon Moon, Young-Ah Shin, Min Jin Go, Jong-Young Lee, and Yoon Shin Cho
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- 2010
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15. Prediction of Ribosomal -1 Frameshifts in the Escherichia coli K12 Genome.
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Sanghoon Moon, Yanga Byun, and Kyungsook Han
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- 2006
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16. Web Service for Finding Ribosomal Frameshifts.
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Yanga Byun, Sanghoon Moon, and Kyungsook Han
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- 2006
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17. Prediction of Readthroughs Based on the Statistical Analysis of Nucleotides Around Stop Codons.
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Sanghoon Moon, Yanga Byun, and Kyungsook Han
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- 2006
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18. Prediction of Ribosomal Frameshift Signals of User-Defined Models.
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Yanga Byun, Sanghoon Moon, and Kyungsook Han
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- 2005
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19. Genome-wide association studies identify two novel loci conferring susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes
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Minoru Iwata, Jeeyun Ahn, Masao Toyoda, Shin-ichi Araki, Lucia Sobrin, Momoko Horikoshi, M Imamura, Gayatri Susarla, Shiro Maeda, Sanghoon Moon, Atsushi Takahashi, Hiroshi Maegawa, Masatoshi Matsunami, Toshimasa Yamauchi, Jinhwa Kong, Takashi Kadowaki, Kazuyuki Tobe, and Kyu Hyung Park
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Genotype ,Genome-wide association study ,Single-nucleotide polymorphism ,Type 2 diabetes ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Asian People ,Gene Frequency ,Japan ,Meta-Analysis as Topic ,Genetics ,medicine ,Genetic predisposition ,Humans ,SNP ,Genetic Predisposition to Disease ,Association Studies Article ,Molecular Biology ,Alleles ,Genetics (clinical) ,030304 developmental biology ,Genetic association ,0303 health sciences ,Diabetic Retinopathy ,030305 genetics & heredity ,Membrane Proteins ,Correction ,General Medicine ,Diabetic retinopathy ,Phosphoproteins ,medicine.disease ,Diabetes Mellitus, Type 2 ,Hexosyltransferases ,Genetic Loci ,Genome-Wide Association Study ,Retinopathy - Abstract
Several reports have suggested that genetic susceptibility contributes to the development and progression of diabetic retinopathy. We aimed to identify genetic loci that confer susceptibility to diabetic retinopathy in Japanese patients with type 2 diabetes. We analysed 5 790 508 single nucleotide polymorphisms (SNPs) in 8880 Japanese patients with type 2 diabetes, 4839 retinopathy cases and 4041 controls, as well as 2217 independent Japanese patients with type 2 diabetes, 693 retinopathy cases and 1524 controls. The results of these two genome-wide association studies (GWAS) were combined with an inverse variance meta-analysis (Stage-1), followed by de novo genotyping for the candidate SNP loci (P
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- 2021
20. Computational Identification of -1 Frameshift Signals.
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Sanghoon Moon, Yanga Byun, and Kyungsook Han
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- 2004
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21. KAREBrowser: SNP database of Korea Association REsource project.
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Chang Bum Hong, Young Jin Kim, Sanghoon Moon, Young-Ah Shin, Yoon Shin Cho, and Jong-Young Lee
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- 2010
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22. FSDB: A frameshift signal database.
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Sanghoon Moon, Yanga Byun, and Kyungsook Han
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- 2007
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23. A general computational model for predicting ribosomal frameshifts in genome sequences.
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Yanga Byun, Sanghoon Moon, and Kyungsook Han
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- 2007
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24. KGVDB: a population-based genomic map of CNVs tagged by SNPs in Koreans.
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Sanghoon Moon, Kwang Su Jung, Young Jin Kim, Mi Yeong Hwang, Kyungsook Han, Jong-Young Lee, Kiejung Park, and Bong-Jo Kim
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- 2013
- Full Text
- View/download PDF
25. Programmable Nuclease-Based Integration into Novel Extragenic Genomic Safe Harbor Identified from Korean Population-Based CNV Analysis
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Bong-Jo Kim, Hyongbum Kim, Seokjoong Kim, Mi Yeong Hwang, Young-Jin Kim, Yun Kyoung Kim, Kwaku Dad Abu-Bonsrah, Eun-Seo Lee, Nathaniel S. Hwang, and Sanghoon Moon
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0301 basic medicine ,Cancer Research ,Transgene ,In silico ,Population ,Biology ,lcsh:RC254-282 ,Article ,03 medical and health sciences ,0302 clinical medicine ,TALEN ,Genotype ,copy number variation region ,genome editing ,Pharmacology (medical) ,education ,Gene ,Genetic association ,Genetics ,Transcription activator-like effector nuclease ,education.field_of_study ,lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,030104 developmental biology ,Oncology ,030220 oncology & carcinogenesis ,Molecular Medicine ,Expression cassette ,safe harbor - Abstract
Here, we found two genomic safe harbor (GSH) candidates from chromosomes 3 and 8, based on large-scale population-based cohort data from 4,694 Koreans by CNV analysis. Furthermore, estimated genotype of these CNVRs was validated by quantitative real-time PCR, and epidemiological data examined no significant genetic association between diseases or traits and two CNVRs. After screening the GSH candidates by in silico approaches, we designed TALEN pairs to integrate EGFP expression cassette into human cell lines in order to confirm the functionality of GSH candidates in an in vitro setting. As a result, transgene insertion into one of the two loci using TALEN showed robust transgene expression comparable to that with an AAVS1 site without significantly perturbing neighboring genes. Changing the promoter or cell type did not noticeably disturb this trend. Thus, we could validate two CNVRs as a site for effective and safe transgene insertion in human cells. Keywords: genome editing, TALEN, safe harbor, copy number variation region
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- 2019
26. Multiple genotype–phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population
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Sungho Won, Young Ho Lee, Sanghoon Moon, and Juyoung Lee
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Male ,0301 basic medicine ,Muscle Proteins ,lcsh:Medicine ,Type 2 diabetes ,Cohort Studies ,0302 clinical medicine ,Polymorphism (computer science) ,Drug Discovery ,Genetics ,Microfilament Proteins ,Middle Aged ,Metabolic syndrome ,Cardiovascular Diseases ,030220 oncology & carcinogenesis ,Nucleotide Transport Proteins ,Intronic SNP ,Molecular Medicine ,Female ,Primary Research ,Adult ,SIDT2 ,Genotype ,lcsh:QH426-470 ,Multiple traits ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Republic of Korea ,medicine ,Humans ,SNP ,Genetic Predisposition to Disease ,Molecular Biology ,Genetic Association Studies ,Aged ,Genetic association ,lcsh:R ,Genetic Variation ,Multiple variants ,medicine.disease ,Introns ,Human genetics ,lcsh:Genetics ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,11q23.3 - Abstract
Background Metabolic syndrome is a risk factor for type 2 diabetes and cardiovascular disease. We identified common genetic variants that alter the risk for metabolic syndrome in the Korean population. To isolate these variants, we conducted a multiple-genotype and multiple-phenotype genome-wide association analysis using the family-based quasi-likelihood score (MFQLS) test. For this analysis, we used 7211 and 2838 genotyped study subjects for discovery and replication, respectively. We also performed a multiple-genotype and multiple-phenotype analysis of a gene-based single-nucleotide polymorphism (SNP) set. Results We found an association between metabolic syndrome and an intronic SNP pair, rs7107152 and rs1242229, in SIDT2 gene at 11q23.3. Both SNPs correlate with the expression of SIDT2 and TAGLN, whose products promote insulin secretion and lipid metabolism, respectively. This SNP pair showed statistical significance at the replication stage. Conclusions Our findings provide insight into an underlying mechanism that contributes to metabolic syndrome. Electronic supplementary material The online version of this article (10.1186/s40246-018-0180-4) contains supplementary material, which is available to authorized users.
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- 2018
27. The trans-ancestral genomic architecture of glycemic traits
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Albertine J. Oldehinkel, Wieland Kiess, Xueling Sim, Norihiro Kato, Philippe Froguel, Astrid van Hylckama Vlieg, Josée Dupuis, Nanette R. Lee, Symen Ligthart, Harry Campbell, Marta E. Alarcón-Riquelme, P. Eline Slagboom, Massimo Mangino, Tian Xie, Niek Verweij, James B. Meigs, Chaolong Wang, Michael Y. Tsai, Erik Ingelsson, Colin N. A. Palmer, Erik B. van den Akker, Fumihiko Matsuda, Rainer Rauramaa, Yi-Cheng Chang, Lars Lind, Stefan R. Bornstein, Mandy Vogel, Sven Bergmann, Ya X. Wang, Ching-Ti Liu, Annette Schürmann, Michael Boehnke, David J. Porteous, Kazuya Setoh, Qibin Qi, Ayse Demirkan, Francesco Cucca, Allan Linneberg, Claire J. Steves, Jun Liu, Leslie A. Lange, Noël P. Burtt, Diana Kuh, Cassandra N. Spracklen, Ken K. Ong, Charumathi Sabanayagam, Jost B. Jonas, Ele Ferrannini, Lawrence J. Beilin, Qing Duan, Blair H. Smith, Isobel D. Stewart, Alexander P. Reiner, Simon P. Mooijaart, Tim D. Spector, Paul W. Franks, E. Shyong Tai, Mark I. McCarthy, Anna L. Gloyn, D.I. Boomsma, Dennis Raven, Nicholas J. Timpson, Rona J. Strawbridge, George Dedoussis, Susan Redline, Jaeyoung Hong, Harald Grallert, Jagadish Vangipurapu, Rico Rueedi, Diane M. Becker, Marian Beekman, Claudia P. Cabrera, Johannes Waage, Jin Fang Chai, Yii-Der Ida Chen, Graciela E. Delgado, Thibaud S. Boutin, Yang Hai, Yoriko Heianza, Wei Zhao, Andres Metspalu, Tien Yin Wong, Mila Desi Anasanti, Inger Njølstad, Hans Bisgaard, Valeriya Lyssenko, Denis Rybin, Wanqing Wen, Torben Hansen, James F. Wilson, Sameline Grimsgaard, Annette Peters, Michele K. Evans, Damia Noce, Sarah C. Nelson, May E. Montasser, Nan Wang, Geltrude Mingrone, Gudny Eiriksdottir, Nicholas J. Wareham, Fouad Kandeel, Linda S. Adair, Kelvin Lam, Jaana Lindström, Eco J. C. de Geus, Debbie A Lawlor, Sara M. Willems, Xu Lin, Harold Snieder, Matt J. Neville, Naveed Sattar, Chelsea K. Raulerson, Paul M. Ridker, Jer-Yuarn Wu, Weihua Zhang, H. Janaka de Silva, Jana V. van Vliet-Ostaptchouk, Elena Tremoli, Toru Nabika, Jing Hua Zhao, Vilmundur Gudnason, Tao Huang, Robert C. Kaplan, Sohee Han, Mohammad Hadi Zafarmand, Aaron Leong, Yen-Feng Chiu, Kumaraswamy Naidu Chitrala, Ivana Kolcic, Franco Giulianini, Tao Wang, Lu Qi, Stephan J. L. Bakker, Laura J Corbin, Zoltán Kutalik, Bruna Gigante, Willa A. Hsueh, Peter J. van der Most, Tin Louie, Yujie Wang, Stella Trompet, Fernando Rivideneira, Yasumasa Ohyagi, Lynne E. Wagenknecht, Jerry L. Nadler, Michael Stumvoll, Mark O. Goodarzi, Sahoko Ichihara, Jeffrey R. O'Connell, Tomohiro Katsuya, Giorgio Pistis, Alice Stanton, Sirkka Keinänen-Kiukaanniemi, Momoko Horikoshi, Honglan Li, Tanja G. M. Vrijkotte, Caroline Hayward, Karen L. Mohlke, Carola Marzi, Girish N. Nadkarni, Laura J. Rasmussen-Torvik, Alain G. Bertoni, Andrew R. Wood, Annique Claringbould, Mi Yeong Hwang, Hugh Watkins, Heikki A. Koistinen, Mattias Frånberg, Jani Heikkinen, Elizabeth Selvin, Donald W. Bowden, Abbas Dehghan, Christian Fuchsberger, Audrey Y. Chu, Kent D. Taylor, Katherine A. Kentistou, Johanna Kuusisto, Jingyi Tan, Huaixing Li, Eric Boerwinkle, Catharina A. Hartman, Archie Campbell, Kari E. North, Oluf Pedersen, Sölve Elmståhl, Emil V. R. Appel, Chang-Hsun Hsieh, Dennis O. Mook-Kanamori, Rob M. van Dam, Pontiano Kaleebu, Corri Black, Jennifer A. Brody, Bengt Sennblad, Shaofeng Huo, M. Larissa Avilés-Santa, Ruth J. F. Loos, Patricia B. Munroe, Chien-Hsiun Chen, Liang Sun, Zorayr Arzumanyan, Rebecca Rohde, Yasuharu Tabara, Albert V. Smith, Betina H. Thuesen, Niels Grarup, Jorgen Engmann, Tatijana Zemunik, M. Arfan Ikram, Marit E. Jørgensen, Christian Herder, Ching-Yu Cheng, Serena Sanna, Damiano Baldassarre, Tarunveer S. Ahluwalia, Mark J. Caulfield, Anne Ndungu, Carl D. Langefeld, Lisa R. Yanek, Luigi Ferrucci, Ananda R. Wickremasinghe, Raymond Noordam, Trevor A. Mori, Tom Wilsgaard, Mika Kivimäki, Rita R. Kalyani, Alan B. Zonderman, Veronique Vitart, Patricia A. Peyser, Shuiqing Lai, Richa Saxena, Li-Ching Chang, Karin Leander, Wei Huang, Peter Vollenweider, Tanya M. Teslovich, Ying Wu, Shufa Du, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Stephen C. J. Parker, Tamar Sofer, Winfried März, Sharon L.R. Kardia, Peter K. Joshi, Neil R. Robertson, Anny H. Xiang, Fumihiko Takeuchi, N. Amin, Jouke-Jan Hottenga, Carol A. Wang, Stefan Gustafsson, Jung Ho Gong, Penny Gordon-Larsen, Yu-Tang Gao, Abhishek Nag, Gonneke Willemsen, Michael A. Province, Aliki-Eleni Farmaki, Segun Fatumo, Antje Körner, Pim van der Harst, Marie Loh, Kei Hang Katie Chan, Gonçalo R. Abecasis, Nicholette D. Palmer, Simin Liu, Ishminder K. Kooner, Javier Gayán, Arne Astrup, Laura J. Scott, Erwin P. Bottinger, Andrew Wong, Inga Prokopenko, Ping An, Markku Laakso, Matthias Blüher, Susan R. Heckbert, Thomas A. Buchanan, Tatsuaki Matsubara, Andrew P. Morris, Brian H. Chen, Kristi Läll, Teresa Tusie, Timo A. Lakka, Jie Yao, Michael Preuss, Teemu Kuulasmaa, Carlos Lorenzo, Stephen S. Rich, Marie Lauzon, Laura M. Raffield, Pankow S. James, Takahisa Kawaguchi, Kathleen A. Ryan, Wei Zheng, Igor Rudan, Thomas Sparsø, Hugoline G. de Haan, Sandosh Padmanabhan, Richard M. Watanabe, Alicia Huerta-Chagoya, Anette P. Gjesing, Andrew A. Hicks, Richard N. Bergman, Mitsuhiro Yokota, Heather M. Stringham, Bruce M. Psaty, Jian'an Luan, Anuj Goel, Eleanor Wheeler, Masahiro Nakatochi, Young-Jin Kim, Xiao-Ou Shu, Mickaël Canouil, Robert A. Scott, Marika Kaakinen, Mari Nelis, Adolfo Correa, Jaspal S. Kooner, Michiya Igase, Anubha Mahajan, Peter E. H. Schwarz, Craig E. Pennell, Claudia Schurmann, Xiaoran Chai, Ji Chen, Lori L. Bonnycastle, Peter S. Sever, Thorkild I. A. Sørensen, André G. Uitterlinden, Ilja M. Nolte, Gaëlle Marenne, Timothy M. Frayling, Bong-Jo Kim, Kerrin S. Small, Cecilia M. Lindgren, Bernhard O. Böhm, Shih-Yi Lin, Katharina E. Schraut, Cornelia M. van Duijn, Sanghoon Moon, Mark Walker, Chiea Chuen Khor, Ruifang Li-Gao, Qiuyin Cai, Neil Schneiderman, Ko Willems van Dijk, Ozren Polasek, W. Craig Johnson, Dermot F. Reilly, Inês Barroso, Anke Tönjes, Manjinder S. Sandhu, Wen B. Wei, Jose C. Florez, Lorraine Southam, Leif Groop, Lawrence F. Bielak, Peter Kovacs, Jianjun Liu, Jouko Saramies, Helen R. Warren, Man Li, Daniel I. Chasman, Eleftheria Zeggini, Xiaoshuai Zhang, Loic Yengo, Shi Jinxiu, Jirong Long, Xiuqing Guo, Meena Kumari, Leslie J. Raffel, Jill M. Norris, Henrik Vestergaard, Jing He, Peter P. Pramstaller, Diana van Heemst, Kevin Sandow, Marjo-Ritta Jarvelin, Carlos A. Aguilar-Salinas, Peitao Wu, Hortensia Moreno-Macías, Jerome I. Rotter, Kathryn Roll, Frits R. Rosendaal, Bernardo L. Horta, Heming Wang, Fernando Pires Hartwig, Richard A. Jensen, Matti Uusitupa, Rozenn N. Lemaitre, Paul R. H. J. Timmers, Timo Saaristo, Jaakko Tuomilehto, Reedik Mägi, Debashree Ray, J. Wouter Jukema, Claudia Langenberg, Marcus E. Kleber, Francis S. Collins, Klaus Bønnelykke, Lenore J. Launer, Arushi Varshney, Anders Hamsten, European Commission, Génétique, génomique fonctionnelle et biotechnologies (UMR 1078) (GGB), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-EFS-Institut National de la Santé et de la Recherche Médicale (INSERM), Sanger Institute, Wellcome Trust, Marenne, Gaëlle [0000-0002-4363-7170], Varshney, Arushi [0000-0001-9177-9707], Corbin, Laura J [0000-0002-4032-9500], Parker, Stephen CJ [0000-0001-8122-0117], Langenberg, Claudia [0000-0002-5017-7344], Wheeler, Eleanor [0000-0002-8616-6444], Morris, Andrew P [0000-0002-6805-6014], Barroso, Inês [0000-0001-5800-4520], Apollo - University of Cambridge Repository, Lifelines Cohort Study, Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC), de Haan, H.G., van den Akker, E., van der Most, P.J., de Geus, EJC, van Dam, R.M., van Heemst, D., van Hylckama Vlieg, A., van Willems van Dijk, K., de Silva, H.J., van der Harst, P., van Duijn, C., Centre of Excellence in Complex Disease Genetics, HUS Abdominal Center, Institute for Molecular Medicine Finland, Leif Groop Research Group, HUS Internal Medicine and Rehabilitation, Department of Medicine, Department of Biochemistry and Developmental Biology, Helsinki University Hospital Area, University of Helsinki, Clinicum, Department of Public Health, Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, Physiology, AMS - Musculoskeletal Health, AMS - Tissue Function & Regeneration, APH - Mental Health, Nutrition and Health, APH - Methodology, Epidemiology and Data Science, ACS - Atherosclerosis & ischemic syndromes, APH - Aging & Later Life, ARD - Amsterdam Reproduction and Development, Public and occupational health, Epidemiology, Internal Medicine, Life Course Epidemiology (LCE), Groningen Institute for Gastro Intestinal Genetics and Immunology (3GI), Groningen Institute for Organ Transplantation (GIOT), Groningen Kidney Center (GKC), Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Center for Liver, Digestive and Metabolic Diseases (CLDM), and Cardiovascular Centre (CVC)
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Blood Glucose ,Disease risk ,Multifactorial Inheritance ,Glycated Hemoglobin A ,[SDV]Life Sciences [q-bio] ,Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) ,LOCI ,Genome-wide association study ,Type 2 diabetes ,VARIANTS ,GLUCOSE ,Epigenesis, Genetic ,chemistry.chemical_compound ,0302 clinical medicine ,Mechanisms ,WIDE ASSOCIATION ,genetics ,Gene-expression ,HEMOGLOBIN ,ComputingMilieux_MISCELLANEOUS ,11 Medical and Health Sciences ,GENE-EXPRESSION ,Genetics ,Genetics & Heredity ,0303 health sciences ,INSULIN-RESISTANCE ,Genome ,Loci ,1184 Genetics, developmental biology, physiology ,Variants ,ALSPAC ,Physical Chromosome Mapping ,Life Sciences & Biomedicine ,Human ,Quantitative Trait Loci ,Wide association study ,Biology ,Quantitative trait locus ,Article ,White People ,diseases ,MECHANISMS ,Quantitative Trait ,03 medical and health sciences ,Insulin resistance ,Quantitative Trait, Heritable ,SDG 3 - Good Health and Well-being ,Genetic ,Lifelines Cohort Study ,Diabetes mellitus ,medicine ,Humans ,Hemoglobin ,Heritable ,METAANALYSIS ,Alleles ,030304 developmental biology ,Genetic association ,Glycemic ,Glycated Hemoglobin ,Science & Technology ,Genome, Human ,Whites ,Gene Expression Profiling ,DISEASE RISK ,Settore MED/13 - ENDOCRINOLOGIA ,Insulin-resistance ,06 Biological Sciences ,medicine.disease ,Glucose ,chemistry ,Blood Glucose/genetics ,European Continental Ancestry Group/genetics ,Genome-Wide Association Study ,Glycated Hemoglobin A/metabolism ,Multifactorial Inheritance/genetics ,Quantitative Trait Loci/genetics ,Glycated hemoglobin ,030217 neurology & neurosurgery ,Meta analysis ,Epigenesis ,Developmental Biology - Abstract
Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.A trans-ancestry meta-analysis of GWAS of glycemic traits in up to 281,416 individuals identifies 99 novel loci, of which one quarter was found due to the multi-ancestry approach, which also improves fine-mapping of credible variant sets.
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- 2021
28. Trans-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
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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
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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.
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- 2020
29. The Trans-Ancestral Genomic Architecture of Glycaemic Traits
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Hugoline G. de Haan, Andrew A. Hicks, Achilleas Pitsilides, Fernando Pires Hartwig, Richard A. Jensen, Matti Uusitupa, Anders Hamsten, Dennis O. Mook-Kanamori, Zorayr Arzumanyan, Betina H. Thuesen, Karin Leander, Fernando Rivideneira, Lynne E. Wagenknecht, Andrew R. Wood, Annique Claringbould, Ele Ferranni, Sölve Elmståhl, Eleanor Wheeler, Sharon L.R. Kardia, Richa Saxena, Tatijana Zemunik, Cassandra N. Spracklen, Ken K. Ong, Xiao-Ou Shu, Johannes Waage, Blair H. Smith, Rozenn N. Lemaitre, Torben Hansen, Peter K. Joshi, Lisa R. Yanek, Neil R. Robertson, Sven Bergmann, Mila Desi Anasanti, Inger Njølstad, Ananda R. Wickremasinghe, Xu Lin, Harold Snieder, Wanqing Wen, Veronique Vitart, Paul R. H. J. Timmers, Timo Saaristo, James F. Wilson, Tian Xie, Tao Huang, Rainer Rauramaa, Kei Hang, Rebecca Rohde, Li-Ching Chang, Jing Hua Zhao, Kazuya Setoh, Yasuharu Tabara, Michael Stumvoll, Mark O. Goodarzi, Igor Rudan, James B. Meigs, Jaakko Tuomilehto, Richard M. Watanabe, Ruth J. F. Loos, Reedik Mägi, Jouke-Jan Hottenga, Ozren Polasek, Michael Y. Tsai, Donald W. Bowden, Diana Kuh, Erik B. van den Akker, Yii-Der Ida Chen, Daniel I. Chasman, Weihua Zhang, Nicholette D. Palmer, Marcus E. Kleber, Anny H. Xiang, Chang-Hsun Hsieh, Alan B. Zonderman, Stefan Gustafsson, Timo A. Lakka, Brian H. Chen, Dermot F. Reilly, Francis S. Collins, Oluf Pedersen, Corri Black, Yang Hai, Zoltán Kutalik, Yoriko Heianza, Willa A. Hsueh, Vilmundur Gudnason, Robert C. Kaplan, Jun Liu, Michael A. Province, Aliki-Eleni Farmaki, Stephen S. Rich, Jian'an Luan, Erik Ingelsson, Marie Loh, Michael Preuss, Lars Lind, Stefan R. Bornstein, Mandy Vogel, Colin N. A. Palmer, Fumihiko Matsuda, Takahisa Kawaguchi, Sohee Han, Ching-Ti Liu, Young-Jin Kim, L. Southam, Sara M. Willems, Mickaël Canouil, Robert A. Scott, Marika Kaakinen, Stephan J. L. Bakker, Momoko Horikoshi, Tarunveer S. Ahluwalia, Annette Schürmann, Graciela E. Delgado, Thibaud S. Boutin, Thomas Sparsø, Sandosh Padmanabhan, Fouad Kandeel, Eco J. C. de Geus, Anubha Mahajan, Claudia Schurmann, Klaus Bønnelykke, Leslie A. Lange, Qing Duan, Rona J. Strawbridge, Dennis Raven, Gonçalo R. Abecasis, Mitsuhiro Yokota, Jani Heikkinen, Elizabeth Selvin, Audrey Y. Chu, Anke Tönjes, Marta E. Alarcón-Riquelme, Hans Bisgaard, P. Eline Slagboom, Eric Boerwinkle, Massimo Mangino, Catharina A. Hartman, Geltrude Mingrone, Lenore J. Launer, Michael Boehnke, Emil V. R. Appel, Niels Grarup, Arushi Varshney, Archie Campbell, Kari E. North, W. Craig Johnson, Inês Barroso, Ya X. Wang, Carola Marzi, Anuj Goel, Eleftheria Zeggini, Lu Qi, Yasumasa Ohyagi, Tien Yin Wong, Tanja G. M. Vrijkotte, Gudny Eiriksdottir, Harald Grallert, Ishminder K. Kooner, Trevor A. Mori, Jagadish Vangipurapu, Laura J Corbin, Tomohiro Katsuya, Wen B. Wei, Segun Fatumo, Debashree Ray, Annette Peters, Lori L. Bonnycastle, Ilja M. Nolte, M. Arfan Ikram, Manjinder S. Sandhu, Marit E. Jørgensen, Christian Herder, Damia Noce, Sarah C. Nelson, Chien-Hsiun Chen, Heather M. Stringham, Yong-Bing Xiang, Bruce M. Psaty, Alain G. Bertoni, Gaëlle Marenne, Timothy M. Frayling, Jose C. Florez, Penny Gordon-Larsen, Yu-Tang Gao, Abhishek Nag, Damiano Baldassarre, J. Wouter Jukema, Wei Huang, Yi-Cheng Chang, Albertine J. Oldehinkel, Xiaoshuai Zhang, Yujie Wang, Shaofeng Huo, Xueling Sim, Norihiro Kato, Bernhard O. Böhm, Lorraine Southam, Mari Nelis, Gonneke Willemsen, Laura J. Rasmussen-Torvik, Philippe Froguel, Charumathi Sabanayagam, Leif Groop, Loic Yengo, Shi Jinxiu, Adolfo Correa, Serena Sanna, Arne Astrup, Teemu Kuulasmaa, Symen Ligthart, Shih-Yi Lin, David J. Porteous, Harry Campbell, Peter Vollenweider, Mark J. Caulfield, Kristi Läll, Anne Ndungu, Carl D. Langefeld, Tanya M. Teslovich, Heikki A. Koistinen, Ying Wu, Mattias Frånberg, D.I. Boomsma, Lawrence F. Bielak, Diana van Heemst, Peter Kovacs, Markku Laakso, Leslie J. Raffel, Katharina E. Schraut, Noël P. Burtt, Michiya Igase, Craig E. Pennell, Claudia Langenberg, Huaixing Li, Teresa Tusie, Laura M. Raffield, Jorgen Engmann, Stephen C. J. Parker, Michele K. Evans, Chaolong Wang, Rico Rueedi, Jianjun Liu, Pankow S. James, Hortensia Moreno-Macías, Fumihiko Takeuchi, Cornelia M. van Duijn, Sanghoon Moon, Susan R. Heckbert, Thomas A. Buchanan, Ko Willems van Dijk, Toru Nabika, May E. Montasser, Caroline Hayward, Jie Yao, Aaron Leong, Antje Körner, Jouko Saramies, Jost B. Jonas, Pim van der Harst, Naveed Sattar, Helen R. Warren, Alice Stanton, Yen-Feng Chiu, Kumaraswamy Naidu Chitrala, Mi Yeong Hwang, Jin Fang Chai, Alicia Huerta-Chagoya, Anette P. Gjesing, Ching-Yu Cheng, Debbie A Lawlor, Simin Liu, Man Li, Ivana Kolcic, Erwin P. Bottinger, Andrew Wong, Stella Trompet, Heming Wang, Jirong Long, Xiuqing Guo, Jeffrey R. O'Connell, Meena Kumari, Sirkka Keinänen-Kiukaanniemi, Rita R. Kalyani, Bengt Sennblad, Mohammad Hadi Zafarmand, Kent D. Taylor, Katherine A. Kentistou, Carol A. Wang, Shuiqing Lai, Patricia B. Munroe, Patricia A. Peyser, Lawrence J. Beilin, Niek Verweij, Inga Prokopenko, Brian E. Cade, Patrik K. E. Magnusson, John C. Chambers, Tamar Sofer, Ping An, Matthias Blüher, Isobel D. Stewart, Alexander P. Reiner, Anna L. Gloyn, Simon P. Mooijaart, Tim D. Spector, Paul W. Franks, Wei Zhao, Andres Metspalu, Wieland Kiess, Kathleen A. Ryan, Astrid van Hylckama Vlieg, Jaana Lindström, Wei Zheng, E. Shyong Tai, Josée Dupuis, Nanette R. Lee, Laura J. Scott, Nicholas J. Timpson, George Dedoussis, Mark I. McCarthy, Tatsuaki Matsubara, Carlos Lorenzo, Denis Rybin, Luigi Ferruci, Chelsea K. Raulerson, Mika Kivimäki, Paul M. Ridker, Jer-Yuarn Wu, Shufa Du, Jaeyoung Hong, Linda S. Adair, Tin Louie, Valeriya Lyssenko, Susan Redline, Kelvin Lam, Qibin Qi, H. Janaka de Silva, Jana V. van Vliet-Ostaptchouk, Peter J. van der Most, Sahoko Ichihara, Nicholas J. Wareham, Ayse Demirkan, Francesco Cucca, Allan Linneberg, Rob M. van Dam, Claire J. Steves, Liang Sun, Albert V. Smith, Raymond Noordam, Tom Wilsgaard, Winfried März, Jung Ho Gong, Matt J. Neville, Jerry L. Nadler, Giorgio Pistis, Karen L. Mohlke, Bruna Gigante, Jennifer A. Brody, Andrew P. Morris, Marie Lauzon, Peter E. H. Schwarz, Bernardo L. Horta, Xiaoran Chai, Ji Chen, Peter S. Sever, Thorkild I. A. Sørensen, André G. Uitterlinden, Javier Gayán, Elena Tremoli, Girish N. Nadkarni, Najaf Amin, Hugh Watkins, Johanna Kuusisto, Jingyi Tan, Sameline Grimsgaard, Bong-Jo Kim, Kerrin S. Small, Jill M. Norris, Cecilia M. Lindgren, Richard N. Bergman, Mark Walker, Henrik Vestergaard, Larissa Aviles-Santa, Jing He, Masahiro Nakatochi, Peter P. Pramstaller, Chiea Chuen Khor, Ruifang Li-Gao, Qiuyin Cai, Neil Schneiderman, Kevin Sandow, Jaspal S. Kooner, Carlos A. Aguilar-Salinas, Peitao Wu, Jerome I. Rotter, Kathryn Roll, Frits R. Rosendaal, Diane M. Becker, Marian Beekman, Claudia P. Cabrera, Nan Wang, Franco Giulianini, Tao Wang, Honglan Li, Abbas Dehghan, Christian Fuchsberger, and Pontiano Kaleebu
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0303 health sciences ,medicine.medical_specialty ,business.industry ,Type 2 diabetes ,medicine.disease ,Fasting insulin ,Fasting glucose ,03 medical and health sciences ,0302 clinical medicine ,Endocrinology ,Internal medicine ,Diabetes mellitus ,medicine ,Genomic architecture ,business ,Glycated haemoglobin ,030217 neurology & neurosurgery ,030304 developmental biology ,Genetic association - Abstract
Glycaemic traits are used to diagnose and monitor type 2 diabetes, and cardiometabolic health. To date, most genetic studies of glycaemic traits have focused on individuals of European ancestry. Here, we aggregated genome-wide association studies in up to 281,416 individuals without diabetes (30% non-European ancestry) with fasting glucose, 2h-glucose post-challenge, glycated haemoglobin, and fasting insulin data. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P-8), 80% with no significant evidence of between-ancestry heterogeneity. Analyses restricted to European ancestry individuals with equivalent sample size would have led to 24 fewer new loci. Compared to single-ancestry, equivalent sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase understanding of diabetes pathophysiology by use of trans-ancestry studies for improved power and resolution.
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- 2020
30. Obesity susceptible novel DNA methylation marker on regulatory region of inflammation gene: results from the Korea Epigenome Study (KES)
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Jun Ho Yun, Nak-Hyeon Choi, Bong-Jo Kim, Jinhwa Kong, Song Cheol Kim, Hyo Jin Kim, Ho-Yeong Yu, Kibaick Lee, Sanghoon Moon, In-Uk Koh, and Song Lee
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obesity ,Endocrinology, Diabetes and Metabolism ,Regulatory Sequences, Nucleic Acid ,Childhood obesity ,Diseases of the endocrine glands. Clinical endocrinology ,03 medical and health sciences ,Epigenome ,0302 clinical medicine ,Gene expression ,Republic of Korea ,medicine ,Humans ,inflammation markers ,030212 general & internal medicine ,Epigenetics ,Gene ,030304 developmental biology ,Genetics ,Inflammation ,0303 health sciences ,business.industry ,cohort ,DNA Methylation ,medicine.disease ,RC648-665 ,Obesity ,CpG site ,Diabetes Mellitus, Type 2 ,DNA methylation ,CpG Islands ,business ,metabolism ,Obesity Studies ,Genome-Wide Association Study - Abstract
IntroductionObesity is growing global health concern and highly associated with increased risk of metabolic diseases including type 2 diabetes. We aimed to discover new differential DNA methylation patterns predisposing obesity and prioritize surrogate epigenetic markers in Koreans.Research design and methodsWe performed multistage epigenome-wide analyses to identify differentially expressed CpGs in obesity using the Illumina HumanMethylationEPIC array (EPIC). Forty-eight CpGs showed significant differences across three phases: 902 whole blood DNAs from two cohorts (phase 1: n=450, phase 2: n=377) and a hospital-based sample (phase 3: n=75). Samples from phase III participants were used to examine whether the 48 CpGs are significant in the fat tissue and influenced gene expression. Furthermore, we investigated the epigenetic effect of CpG loci in childhood obesity (n=94).ResultsSeven of the 48 CpGs exhibited similar changes in the fat tissue along with gene expression changes. In particular, hypomethylated CpG (cg13424229) on the GATA1 transcription factor cluster of CPA3 promoter was related to its increased gene expression and showed consistent effect in childhood obesity. Interestingly, subsequent analysis using RNA sequencing data from 21 preadipocytes and 26 adipocytes suggested CPA3 as a potential obesity-related gene. Moreover, expression patterns from RNA sequencing and public Gene Expression Omnibus showed the correlation between CPA3 and type 2 diabetes (T2D) and asthma.ConclusionsOur finding prioritizes influential genes in obesity and provides new evidence for the role of CPA3 linking obesity, T2D, and asthma.
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- 2020
31. Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels
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Alan B. Feranil, Cassandra N. Spracklen, Sing-Hui Lim, Cathy S.J. Fann, Tin Aung, Yii-Der Ida Chen, Yonghong Zhang, Li-Hsin Chien, Jirong Long, Xiuqing Guo, Chien-Hsiun Chen, Jyh-Ming Jimmy Juang, Fumihiko Takeuchi, Xueling Sim, Norihiro Kato, Wen-Harn Pan, Masato Isono, Tzung-Dau Wang, Jer-Yuarn Wu, Dongfeng Gu, Xu Wang, Xuhong Hou, Peng Chen, Wen-Jane Lee, Kae-Woei Liang, Sun-Ju Lee, Chao A. Hsiung, Meian He, Lee-Ming Chuang, Devin Absher, Chii-Min Hwu, Tangchun Wu, Li-Ching Chang, Sanghoon Moon, Mi Yeong Hwang, Chew-Kiat Heng, Sun Ha Jee, Feijie Wang, Yik Ying Teo, Kent D. Taylor, Shufa Du, Wen Bin Wei, Ching-Yu Cheng, I-Te Lee, Elias Salfati, Jie Wang, Cheng Hu, Chiea Chuen Khor, Qiuyin Cai, James E. Hixson, Toru Nabika, Wayne Huey-Herng Sheu, Qiao Fan, Woon-Puay Koh, Linda S. Adair, Jianjun Liu, Pok Chien Tan, Penny Gordon-Larsen, Yechiel Friedlander, Bok-Ghee Han, Keng-Hung Lin, Ying Wu, Hao Peng, E-Shyong Tai, Young-Jin Kim, Koichi Akiyama, Bong-Jo Kim, Rajkumar Dorajoo, Wanting Zhao, Tomohiro Katsuya, Stephen S. Rich, Sue-Anne Toh, Rong Zhang, Shengxu Li, Yuan-Tsong Chen, Ya Xing Wang, Keum Ji Jung, Xu Lin, Zhirong Guo, Wei Zheng, Karen L. Mohlke, Shu-Pei Tan, Rob M. van Dam, Liang Sun, Jiang He, Lixuan Gui, Tatsuhiko Tsunoda, Hui Cai, Aili Wang, Huaixing Li, Wei Huang, Yao Hu, Kevin Sandow, Toshihiro Tanaka, Thomas Quertermous, Themistocles L. Assimes, Jerome I. Rotter, Maren E Cannon, Tamara S. Roman, Yong-Bing Xiang, Yoon Shin Cho, Todd A. Johnson, Shi Jinxiu, Weiping Jia, Tien Yin Wong, Yun Kyoung Kim, Jie Yao, Xiao-Ou Shu, Jian-Min Yuan, Blanche Lim, Michiaki Kubo, Shu-Chun Chuang, Charumathi Sabanayagam, and Jost B. Jonas
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Adult ,Male ,0301 basic medicine ,Linkage disequilibrium ,Quantitative Trait Loci ,Locus (genetics) ,Genome-wide association study ,Quantitative trait locus ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,White People ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Asian People ,Gene Frequency ,Ethnicity ,Genetics ,Humans ,Allele ,Molecular Biology ,Allele frequency ,Alleles ,Genetic Association Studies ,Triglycerides ,Genetics (clinical) ,Genetic association ,Cholesterol ,Association Studies Articles ,General Medicine ,Middle Aged ,Lipids ,Lipoproteins, LDL ,030104 developmental biology ,chemistry ,Female ,Lipoproteins, HDL ,Corrigendum ,030217 neurology & neurosurgery ,Genome-Wide Association Study - Abstract
Large-scale meta-analyses of genome-wide association studies (GWAS) have identified >175 loci associated with fasting cholesterol levels, including total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and triglycerides (TG). With differences in linkage disequilibrium (LD) structure and allele frequencies between ancestry groups, studies in additional large samples may detect new associations. We conducted staged GWAS meta-analyses in up to 69,414 East Asian individuals from 24 studies with participants from Japan, the Philippines, Korea, China, Singapore, and Taiwan. These meta-analyses identified (P
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- 2017
32. Identification of a Copy Number Variation on Chromosome 20q13.12 Associated with Osteoporotic Fractures in the Korean Population
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Mi Yeong Hwang, Bong-Jo Kim, Min Jin Go, Taejoon Park, Joo-Yeon Hwang, and Sanghoon Moon
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0301 basic medicine ,DNA copy number variations ,lcsh:QH426-470 ,Osteoporosis ,real-time polymerase chain reaction ,Health Informatics ,Genome-wide association study ,osteoporotic fracture ,Bioinformatics ,Logistic regression ,03 medical and health sciences ,Genetics ,Medicine ,Copy-number variation ,Ecology, Evolution, Behavior and Systematics ,Genetic association ,genome-wide association study ,business.industry ,Korean population ,Chromosome ,medicine.disease ,3. Good health ,lcsh:Genetics ,030104 developmental biology ,Real-time polymerase chain reaction ,Original Article ,business - Abstract
Osteoporotic fractures (OFs) are critical hard outcomes of osteoporosis and are characterized by decreased bone strength induced by low bone density and microarchitectural deterioration in bone tissue. Most OFs cause acute pain, hospitalization, immobilization, and slow recovery in patients and are associated with increased mortality. A variety of genetic studies have suggested associations of genetic variants with the risk of OF. Genome-wide association studies have reported various single-nucleotide polymorphisms and copy number variations (CNVs) in European and Asian populations. To identify CNV regions associated with OF risk, we conducted a genome-wide CNV study in a Korean population. We performed logistic regression analyses in 1,537 Korean subjects (299 OF cases and 1,238 healthy controls) and identified a total of 8 CNV regions significantly associated with OF (p < 0.05). Then, one CNV region located on chromosome 20q13.12 was selected for experimental validation. The selected CNV region was experimentally validated by quantitative polymerase chain reaction. The CNV region of chromosome 20q13.12 is positioned upstream of a family of long non-coding RNAs, LINC01260. Our findings could provide new information on the genetic factors associated with the risk of OF.
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- 2016
33. Identification of type 2 diabetes loci in 433,540 East Asian individuals
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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
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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.
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- 2019
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34. The Korea Biobank Array: Design and Identification of Coding Variants Associated with Blood Biochemical Traits
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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
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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.
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- 2019
35. Exome chip-driven association study of lipidemia in14,000 Koreans and evaluation of genetic effect on identified variants between different ethnic groups
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Mi Yeong Hwang, Sanghoon Moon, Sohee Han, Bong-Jo Kim, Yun Kyoung Kim, Kyungheon Yoon, and Young-Jin Kim
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Apolipoprotein E ,Male ,Candidate gene ,Apolipoprotein B ,Epidemiology ,Genome-wide association study ,Hyperlipidemias ,Polymorphism, Single Nucleotide ,03 medical and health sciences ,Asian People ,Republic of Korea ,medicine ,Ethnicity ,Humans ,Exome ,Genetics (clinical) ,030304 developmental biology ,Genetics ,0303 health sciences ,biology ,030305 genetics & heredity ,Hypertriglyceridemia ,Lipid metabolism ,Middle Aged ,medicine.disease ,Lipids ,Phenotype ,biology.protein ,lipids (amino acids, peptides, and proteins) ,Female ,Dyslipidemia ,Genome-Wide Association Study - Abstract
Lipid levels in blood are widely used to diagnose and monitor chronic diseases. It is essential to identify the genetic traits involved in lipid metabolism for understanding chronic diseases. However, the influence of genetic traits varies depending on race, sex, age, and ethnicity. Therefore, research focusing on populations of individual countries is required, and the results can be used as a basis for comparison of results of other studies at the cross-racial and cross-country levels. In the present study, we selected lipid-related variants and evaluated their effects on lipid-related diseases in more than 14,000 subjects of three cohorts using the Illumina Human Exome Beadchip. A genome-wide association study was conducted using EPACTs after adjusting for age, sex, and recruitment area. A genome-wide significance cutoff was defined as p
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- 2018
36. Genovar: a detection and visualization tool for genomic variants.
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Kwang Su Jung, Sanghoon Moon, Young Kim, Bong-Jo Kim, and Kiejung Park
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- 2012
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37. Integrated Analysis of Tissue-Specific Promoter Methylation and Gene Expression Profile in Complex Diseases
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Young-Jin Kim, Hee Gyung Kang, Ho Yeong Yu, Nak Hyeon Choi, Kibaick Lee, Sanghoon Moon, Bong Jo Kim, Mi Jin Park, Jinhwa Kong, In Uk Koh, and Song Cheol Kim
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obesity ,Biology ,Article ,Catalysis ,Epigenesis, Genetic ,lcsh:Chemistry ,Inorganic Chemistry ,Animals ,Humans ,Gene Regulatory Networks ,Epigenetics ,Physical and Theoretical Chemistry ,Promoter Regions, Genetic ,lcsh:QH301-705.5 ,Molecular Biology ,Gene ,Spectroscopy ,Genetic association ,Epigenomics ,Genetics ,DNA methylation ,Whole Genome Sequencing ,Genome, Human ,Organic Chemistry ,Promoter ,General Medicine ,Methylation ,Computer Science Applications ,lcsh:Biology (General) ,lcsh:QD1-999 ,Diabetes Mellitus, Type 2 ,CpG site ,Organ Specificity ,CpG Islands ,type 2 diabetes ,Transcriptome ,tissue-specific expression - Abstract
This study investigated whether the promoter region of DNA methylation positively or negatively regulates tissue-specific genes (TSGs) and if it correlates with disease pathophysiology. We assessed tissue specificity metrics in five human tissues, using sequencing-based approaches, including 52 whole genome bisulfite sequencing (WGBS), 52 RNA-seq, and 144 chromatin immunoprecipitation sequencing (ChIP-seq) data. A correlation analysis was performed between the gene expression and DNA methylation levels of the TSG promoter region. The TSG enrichment analyses were conducted in the gene&ndash, disease association network (DisGeNET). The epigenomic association analyses of CpGs in enriched TSG promoters were performed using 1986 Infinium MethylationEPIC array data. A correlation analysis showed significant associations between the promoter methylation and 449 TSGs&rsquo, expression. A disease enrichment analysis showed that diabetes- and obesity-related diseases were high-ranked. In an epigenomic association analysis based on obesity, 62 CpGs showed statistical significance. Among them, three obesity-related CpGs were newly identified and replicated with statistical significance in independent data. In particular, a CpG (cg17075888 of PDK4), considered as potential therapeutic targets, were associated with complex diseases, including obesity and type 2 diabetes. The methylation changes in a substantial number of the TSG promoters showed a significant association with metabolic diseases. Collectively, our findings provided strong evidence of the relationship between tissue-specific patterns of epigenetic changes and metabolic diseases.
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- 2020
38. Discovery and Replication of HDL-Associated Loci in the Korean Population Using 35,000 Individuals
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Young-Jin Kim, Sanghoon Moon, Mi Yeong Hwang, and Bong-Jo Kim
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Genetics ,Minor allele frequency ,Endocrinology, Diabetes and Metabolism ,Cohort ,Internal Medicine ,Genome-wide association study ,International HapMap Project ,Biology ,Association mapping ,Genome ,Imputation (genetics) ,Reference genome - Abstract
Low levels of HDL are known to be associated with increased risk of type 2 diabetes. It has been suggested as a new therapeutic approach that increase HDL levels in plasma. Previously, to identify lipids traits associated loci, we performed large-scale genome-wide meta-analyses comprising 25,923 East Asian individuals from 11 studies from Korea, Japan, Philippines, China, Singapore, and Taiwan in the discovery stage. With subsequent replication study, we have revealed seven novel loci associated with HDL including loci at CD163-APOBEC1, NCOA2, and NID2-PTGDR. However, previous study was limited in sample size in the discovery stage and low association mapping resolution due to HapMap based imputation analysis. In this study, we performed genome-wide association analyses (GWAS) on HDL using about 35,000 Korean samples and imputed based on 1,000 Genomes project phase 3 and Korean Reference Genome. We focused on imputed (imputation quality score >0.4) and genotyped common variants with minor allele frequency >= 1%. In this discovery study, 17 known loci were replicated at the genome-wide significance level (P In summary, we performed a GWAS on HDL using about 35,000 Korean samples. The GWAS confirmed 28 known loci and discovered 10 possible novel candidate loci responsible for variation of HDL level. However, a replication study in an independent cohort is warranted for validating the results. Taken together, the possible novel candidates discovered from this study may provide potential novel therapeutic targets for diseases associated with HDL. Disclosure B. Kim: None. Y. Kim: None. M. Hwang: None. S. Moon: None.
- Published
- 2018
39. Nonsynonymous Variants in
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Soo Heon, Kwak, Jeesoo, Chae, Seungbok, Lee, Sungkyoung, Choi, Bo Kyung, Koo, Ji Won, Yoon, Jin-Ho, Park, Belong, Cho, Min Kyong, Moon, Soo, Lim, Young Min, Cho, Sanghoon, Moon, Young Jin, Kim, Sohee, Han, Mi Yeong, Hwang, Yoon Shin, Cho, Myung-Shik, Lee, Hak C, Jang, Hyun Min, Kang, Taesung, Park, Nam H, Cho, Kyunga, Kim, Jong-Il, Kim, and Kyong Soo, Park
- Subjects
Homeodomain Proteins ,Male ,Computational Biology ,Genetic Variation ,Expert Systems ,Middle Aged ,Polymorphism, Single Nucleotide ,Glucagon-Like Peptide-1 Receptor ,Cohort Studies ,Amino Acid Substitution ,Asian People ,Diabetes Mellitus, Type 2 ,Gene Frequency ,Case-Control Studies ,Databases, Genetic ,Republic of Korea ,Exome Sequencing ,Humans ,Paired Box Transcription Factors ,Female ,Genetic Predisposition to Disease ,Alleles ,Genetic Association Studies ,Aged ,Genome-Wide Association Study - Abstract
We investigated ethnicity-specific exonic variants of type 2 diabetes (T2D) and its related clinical phenotypes in an East Asian population. We performed whole-exome sequencing in 917 T2D case and control subjects, and the findings were validated by exome array genotyping in 3,026 participants. In silico replication was conducted for seven nonsynonymous variants in an additional 13,122 participants. Single-variant and gene-based association tests for T2D were analyzed. A total of 728,838 variants were identified by whole-exome sequencing. Among nonsynonymous variants
- Published
- 2018
40. Genome-based exome sequencing analysis identifies GYG1, DIS3L and DDRGK1 are associated with myocardial infarction in Koreans
- Author
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Bok Ghee Han, Bok Soo Lee, Sang Hak Lee, Yangsoo Jang, Min Young Park, Sanghoon Moon, Yun Kyoung Kim, Jeong Euy Park, and Ji-Young Lee
- Subjects
0301 basic medicine ,Adult ,Male ,Genotype ,Myocardial Infarction ,Genome-wide association study ,030204 cardiovascular system & hematology ,Biology ,Genome ,Polymorphism, Single Nucleotide ,Coronary artery disease ,03 medical and health sciences ,0302 clinical medicine ,Ribonucleases ,Asian People ,Risk Factors ,Exome Sequencing ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,Genetic variability ,Myocardial infarction ,Gene ,Exome sequencing ,Genetic association ,Adaptor Proteins, Signal Transducing ,Glycoproteins ,Middle Aged ,medicine.disease ,030104 developmental biology ,Glucosyltransferases ,Female ,Carrier Proteins ,Genome-Wide Association Study - Abstract
Myocardial infarction (MI) is a complex disease caused by combination of genetic and environmental factors. Although genome-wide association studies (GWAS) identified more than 46 risk loci which are associated with coronary artery disease and MI, most of the genetic variability in MI still remains undefined. Here, we screened the susceptibility loci for MI using exome sequencing and validated candidate variants in replication sets. We identified that three genes (GYG1, DIS3L and DDRGK1) were associated with MI at the discovery and replication stages. Further research will be required to determine the functional association of these genes with MI risk, and these associations have to be confirmed in other ethnic populations.
- Published
- 2018
41. Interethnic analyses of blood pressure loci in populations of East Asian and European descent
- Author
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Xiang Y-B., Charumathi Sabanayagam, Sohee Han, Jirong Long, Dermot F. Reilly, Jiang He, Iona Y Millwood, Masayuki Yamamoto, Zhengming Chen, Yaning Wang, Shu X-O., Derrick A Bennett, Huaixing Li, Karen L. Mohlke, Hiromi Rakugi, Jb Jonas, Sanghoon Moon, Nana Matoba, Xueling Sim, Jovia L. Nierenberg, Norihiro Kato, Juyoung Lee, Eitaro Nakashima, Makoto Hirata, Tatsuaki Matsubara, Kuang Lin, Nanette R. Lee, Liang Zhang, Xiaozhen Lin, Lei Xu, Wei Huang, Koichi Matsuda, Saw W-Y., Michiaki Kubo, Wei Zheng, Katsuhiko Kohara, Atsushi Takahashi, Rajkumar Dorajoo, Lanlan Li, Motohide Isono, Le Sun, Cassandra N. Spracklen, Toru Nabika, W Bin Wei, Chen C-H., Atsushi Hozawa, Masahiro Nakatochi, John C. Chambers, Chaolong Wang, Heng C-K., Jianjun Liu, Wu J-Y., Cheng C-Y., Jaspal S. Kooner, Chen Y-T., Tien Yin Wong, Chai J-F., Koh W-P., Tetsuro Miki, S Huo, Chang L-C., Kim Y-J., Michiya Igase, Linda S. Adair, Yuan J-M., Yasuharu Tabara, Penny Gordon-Larsen, Yechiel Friedlander, Masato Akiyama, Sahoko Ichihara, Robert Clarke, Tai E-S., Todd L. Edwards, Tanika N. Kelly, Teo Y-Y., Miao-Li Chee, Paul Elliott, Ken Yamamoto, Yukihide Momozawa, Weijie Zhao, Yoichiro Kamatani, Matsuyuki Shirota, Kim B-J., Tomohiro Katsuya, Akira Narita, Mi Yeong Hwang, Hui Cai, Mitsuhiro Yokota, Fumihiko Takeuchi, P. van der Harst, Robin G. Walters, Makoto Sasaki, Graduate School, Center of Experimental and Molecular Medicine, CCA - Imaging and biomarkers, CCA - Cancer biology and immunology, AII - Cancer immunology, AGEM - Re-generation and cancer of the digestive system, Epidemiology and Data Science, AGEM - Endocrinology, metabolism and nutrition, AGEM - Inborn errors of metabolism, Laboratory for Experimental Clinical Chemistry, APH - Personalized Medicine, APH - Methodology, Medical Research Council (MRC), National Institute for Health Research, Imperial College Healthcare NHS Trust- BRC Funding, UK DRI Ltd, RS: GROW - R1 - Prevention, Toxicogenomics, and Cardiovascular Centre (CVC)
- Subjects
Male ,0301 basic medicine ,Linkage disequilibrium ,LINKAGE DISEQUILIBRIUM ,General Physics and Astronomy ,Blood Pressure ,Genome-wide association study ,Disease ,lcsh:Science ,Genetics ,International Genomics of Blood Pressure (iGEN-BP) Consortium ,ARCHITECTURE ,Multidisciplinary ,Natural selection ,Continental Population Groups ,HERITABILITY ,3. Good health ,Multidisciplinary Sciences ,Europe ,CARDIOVASCULAR-DISEASE ,RARE VARIANTS ,Science & Technology - Other Topics ,Female ,Medical Genetics ,FUNCTIONAL ANNOTATION ,Asian Continental Ancestry Group ,Science ,European Continental Ancestry Group ,Single-nucleotide polymorphism ,Biology ,Polymorphism, Single Nucleotide ,Article ,White People ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,Asian People ,MD Multidisciplinary ,Humans ,GENOME-WIDE ASSOCIATION ,COMMON ,METAANALYSIS ,Medicinsk genetik ,Science & Technology ,Racial Groups ,General Chemistry ,Heritability ,BODY-MASS INDEX ,030104 developmental biology ,Blood pressure ,Genetic Loci ,lcsh:Q ,Selective sweep ,Genome-Wide Association Study - Abstract
Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, we perform a multi-stage genome-wide association study for BP (max N = 289,038) principally in East Asians and meta-analysis in East Asians and Europeans. We report 19 new genetic loci and ancestry-specific BP variants, conforming to a common ancestry-specific variant association model. At 10 unique loci, distinct non-rare ancestry-specific variants colocalize within the same linkage disequilibrium block despite the significantly discordant effects for the proxy shared variants between the ethnic groups. The genome-wide transethnic correlation of causal-variant effect-sizes is 0.898 and 0.851 for systolic and diastolic BP, respectively. Some of the ancestry-specific association signals are also influenced by a selective sweep. Our results provide new evidence for the role of common ancestry-specific variants and natural selection in ethnic differences in complex traits such as BP., Blood pressure (BP) is a major risk factor for cardiovascular disease and more than 200 genetic loci associated with BP are known. Here, the authors perform discovery GWAS for BP in East Asians and meta-analysis in East Asians and Europeans and report ancestry-specific BP SNPs and selection signals.
- Published
- 2018
42. Additional file 1: of Multiple genotypeâ phenotype association study reveals intronic variant pair on SIDT2 associated with metabolic syndrome in a Korean population
- Author
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Sanghoon Moon, Lee, Young, Sungho Won, and Juyoung Lee
- Abstract
Supplementary information. Figure S1. Screenshot of GTEx database for significant SNP pair rs7107152 and rs1242229. Figure S2. Screenshot of NESDA NTR Conditional eQTL Catalog for rs7107152 and rs1242229. Figure S3. Screenshot of RegulomeDB for rs1242229. Figure S4. Radar chart showing the result of the rs7107152 and rs1242229 SNP pairâ single trait (metabolic syndrome-component trait) association analysis. Figure S5. Screenshot from the GTEx database of the eQTL SNP-enriched region around SIDT2 and TAGLN (chr11:117,000,000-117,100,000). Figure S6 Model for how significant SNP pair rs7107152/rs1242229 may affect metabolic syndrome risk. Table S1. Characteristics of gene-based SNPs set. Table S2. Minor allele frequency of identified SNPs. (PDF 975 kb)
- Published
- 2018
- Full Text
- View/download PDF
43. MicroRNA-650 in a copy number-variable region regulates the production of interleukin 6 in human osteosarcoma cells
- Author
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Bok Ghee Han, Youngsoo Kim, Sanghoon Moon, Jun Ho Yun, Mi Yeong Hwang, Jeong Min Kim, Ho Yeong Yu, Heun Sik Lee, Bong Jo Kim, and Yeon Jung Kim
- Subjects
Genetics ,Cancer Research ,Oncogene ,business.industry ,Interleukin ,Articles ,Cell cycle ,Cell biology ,Oncology ,Gene expression ,microRNA ,Medicine ,Copy-number variation ,business ,Enhancer ,Gene - Abstract
Copy number variation is a well-known genetic variation. microRNAs (miRNAs/miRs) are non-coding RNAs that mediate gene expression by regulating target mRNAs. In the present study, copy number deletions encompassing miRNA coding regions were investigated to determine the association between the deletion of miRNA and its phenotypic effects. A total of 38 human miRNAs in copy number variants were identified and miR-650, which is functional in the human osteosarcoma MG-63 cell line, was selected. Overexpression of miR-650 decreased the expression of inhibitor of growth family member 4 (ING4) in the MG-63 cells and increased interleukin (IL)6 transcription, as well as IL6 secretion in IL1B-stimulated cells. Furthermore, miR-650 downregulated the amount of nuclear factor of κ light polypeptide gene enhancer in B cells inhibitor α and increased the transcriptional activity of nuclear factor (NF)κB. Downregulation of ING4 also increased the production of IL6, similar to miR-650 overexpression. Taken together, these data indicate that miR-650 plays a significant role in the production of IL6 by regulating ING4 expression and NFκB signaling in IL1B-stimulated MG-63 osteosarcoma cells.
- Published
- 2015
44. Genome-Wide Association Study Identifies Candidate Loci Associated with Platelet Count in Koreans
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Young-Jin Kim, Ji Hee Oh, Sanghoon Moon, Bong Jo Kim, and Yun Kyoung Kim
- Subjects
Genetics ,education.field_of_study ,genome-wide association study ,Korea ,lcsh:QH426-470 ,Population ,Health Informatics ,Genome-wide association study ,Arteriosclerosis ,Biology ,platelet count ,medicine.disease ,lcsh:Genetics ,medicine.anatomical_structure ,medicine ,SH2B3 Gene ,Platelet ,Original Article ,Bone marrow ,Platelet activation ,education ,Gene ,Ecology, Evolution, Behavior and Systematics - Abstract
Platelets are derived from the fragments that are formed from the cytoplasm of bone marrow megakaryocytes-small irregularly shaped anuclear cells. Platelets respond to vascular damage, contracts blood vessels, and attaches to the damaged region, thereby stopping bleeding, together with the action of blood coagulation factors. Platelet activation is known to affect genes associated with vascular risk factors, as well as with arteriosclerosis and myocardial infarction. Here, we performed a genome-wide association study with 352,228 single-nucleotide polymorphisms typed in 8,842 subjects of the Korea Association Resource (KARE) project and replicated the results in 7,861 subjects from an independent population. We identified genetic associations between platelet count and common variants nearby chromosome 4p16.1 (p = 1.46 × 10(-10), in the KIAA0232 gene), 6p21 (p = 1.36 × 10(-7), in the BAK1 gene), and 12q24.12 (p = 1.11 × 10(-15), in the SH2B3 gene). Our results illustrate the value of large-scale discovery and a focus for several novel research avenues.
- Published
- 2014
45. On the Analysis of a Repeated Measure Design in Genome-Wide Association Analysis
- Author
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Sungho Won, Woojoo Lee, Suyeon Park, Young Moo Lee, Sanghoon Moon, Robert C. Elston, and Ju Young Lee
- Subjects
Adult ,Male ,Mixed model ,Aging ,longitudinal data ,Genotype ,Health, Toxicology and Mutagenesis ,lcsh:Medicine ,Genome-wide association study ,Biology ,Polymorphism, Single Nucleotide ,Linkage Disequilibrium ,Article ,Epigenesis, Genetic ,Sex Factors ,cross-sectional data ,Korean Association Resource(KARE) cohort ,Health Examinee (HEXA) cohort ,Asian People ,Republic of Korea ,Statistics ,Linear regression ,Humans ,Longitudinal Studies ,Genotyping ,Korean Association Resource (KARE) cohort ,Genetic association ,Genetics ,Cross-sectional data ,lcsh:R ,Public Health, Environmental and Occupational Health ,Repeated measures design ,Middle Aged ,Gene Expression Regulation ,Research Design ,Sample size determination ,Female ,Genome-Wide Association Study - Abstract
Longitudinal data enables detecting the effect of aging/time, and as a repeated measures design is statistically more efficient compared to cross-sectional data if the correlations between repeated measurements are not large. In particular, when genotyping cost is more expensive than phenotyping cost, the collection of longitudinal data can be an efficient strategy for genetic association analysis. However, in spite of these advantages, genome-wide association studies (GWAS) with longitudinal data have rarely been analyzed taking this into account. In this report, we calculate the required sample size to achieve 80% power at the genome-wide significance level for both longitudinal and cross-sectional data, and compare their statistical efficiency. Furthermore, we analyzed the GWAS of eight phenotypes with three observations on each individual in the Korean Association Resource (KARE). A linear mixed model allowing for the correlations between observations for each individual was applied to analyze the longitudinal data, and linear regression was used to analyze the first observation on each individual as cross-sectional data. We found 12 novel genome-wide significant disease susceptibility loci that were then confirmed in the Health Examination cohort, as well as some significant interactions between age/sex and SNPs.
- Published
- 2014
46. Genome-Wide Association Study Meta-Analysis of Long Term Average Blood Pressure in East Asians
- Author
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Santhi K. Ganesh, E-Shyong Tai, Chieh Hsiang Lu, Jie Yao, Jia Yu Koh, Dongfeng Gu, Tanika N. Kelly, Tangchun Wu, Jer-Yuarn Wu, Neelam Kumari, DC Rao, Jinying Zhao, Sohee Han, Liang Sun, Xu Lin, Jerome I. Rotter, Ju Young Lee, Yun Kyoung Kim, Yao Hu, Walter Palmas, Meian He, Lixuan Gui, Kae-Woei Liang, Hua Hu, Chien-Hsiun Chen, Bong-Jo Kim, I-Te Lee, Xueling Sim, Rajkumar Dorajoo, Huaixing Li, Kent D. Taylor, Yik-Ying Teo, Jianjun Liu, Sanghoon Moon, Wayne H-H Sheu, Wen-Jane Lee, Bok-Ghee Han, Yingfeng Zheng, Yii-Der Ida Chen, Tien Yin Wong, Ching-Yu Cheng, Jiang He, Changwei Li, James E. Hixson, Yiqin Wang, Yunfeng He, Xiuqing Guo, Jing Chen, Leslie J. Raffel, and Fuu-Jen Tsai
- Subjects
0301 basic medicine ,Male ,Mean arterial pressure ,Locus (genetics) ,Genome-wide association study ,Blood Pressure ,Biology ,Polymorphism, Single Nucleotide ,Article ,03 medical and health sciences ,Asian People ,Genetics ,Humans ,Gene ,Genetics (clinical) ,Asia, Eastern ,030104 developmental biology ,Blood pressure ,Phenotype ,CYP17A1 ,Genetic Loci ,Meta-analysis ,Female ,ATP2B1 ,Cardiology and Cardiovascular Medicine ,Genome-Wide Association Study - Abstract
Background— Genome-wide single marker and gene-based meta-analyses of long-term average (LTA) blood pressure (BP) phenotypes may reveal novel findings for BP. Methods and Results— We conducted genome-wide analysis among 18 422 East Asian participants (stage 1) followed by replication study of ≤46 629 participants of European ancestry (stage 2). Significant single-nucleotide polymorphisms and genes were determined by a P −8 and 2.5×10 − 6 , respectively, in joint analyses of stage-1 and stage-2 data. We identified 1 novel ARL3 variant, rs4919669 at 10q24.32, influencing LTA systolic BP (stage-1 P =5.03×10 − 8 , stage-2 P =8.64×10 − 3 , joint P =2.63×10 − 8 ) and mean arterial pressure (stage-1 P =3.59×10 − 9 , stage-2 P =2.35×10 − 2 , joint P =2.64×10 − 8 ). Three previously reported BP loci ( WBP1L , NT5C2 , and ATP2B1 ) were also identified for all BP phenotypes. Gene-based analysis provided the first robust evidence for association of KCNJ11 with LTA systolic BP (stage-1 P =8.55×10 − 6 , stage-2 P =1.62×10 − 5 , joint P =3.28×10 − 9 ) and mean arterial pressure (stage-1 P =9.19×10 − 7 , stage-2 P =9.69×10 − 5 , joint P =2.15×10 − 9 ) phenotypes. Fourteen genes ( TMEM180 , ACTR1A , SUFU , ARL3 , SFXN2 , WBP1L , CYP17A1 , C10orf32 , C10orf32 - ASMT , AS3MT , CNNM2 , and NT5C2 at 10q24.32; ATP2B1 at 12q21.33; and NCR3LG1 at 11p15.1) implicated by previous genome-wide association study meta-analyses were also identified. Among the loci identified by the previous genome-wide association study meta-analysis of LTA BP, we transethnically replicated associations of the KCNK3 marker rs1275988 at 2p23.3 with LTA systolic BP and mean arterial pressure phenotypes ( P =1.27×10 − 4 and 3.30×10 − 4 , respectively). Conclusions— We identified 1 novel variant and 1 novel gene and present the first direct evidence of relevance of the KCNK3 locus for LTA BP among East Asians.
- Published
- 2017
47. On the association analysis of CNV data: a fast and robust family-based association method
- Author
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Sungho Won, Meiling Liu, Yeon Jung Kim, Sanghoon Moon, Bong Jo Kim, Sulgi Kim, Longfei Wang, Young-Jin Kim, Robert C. Elston, and Mi Yeong Hwang
- Subjects
0301 basic medicine ,DNA Copy Number Variations ,Computer science ,Family based association ,CNV ,Computational biology ,Association analysis ,lcsh:Computer applications to medicine. Medical informatics ,Biochemistry ,03 medical and health sciences ,Structural Biology ,Humans ,Copy-number variation ,Association (psychology) ,Molecular Biology ,lcsh:QH301-705.5 ,Genetic association ,Genetics ,Applied Mathematics ,Computer Science Applications ,030104 developmental biology ,lcsh:Biology (General) ,Hematocrit ,Score test ,lcsh:R858-859.7 ,Research Article ,Genome-Wide Association Study - Abstract
Background Copy number variation (CNV) is known to play an important role in the genetics of complex diseases and several methods have been proposed to detect association of CNV with phenotypes of interest. Statistical methods for CNV association analysis can be categorized into two different strategies. First, the copy number is estimated by maximum likelihood and association of the expected copy number with the phenotype is tested. Second, the observed probe intensity measurements can be directly used to detect association of CNV with the phenotypes of interest. Results For each strategy we provide a statistic that can be applied to extended families. The computational efficiency of the proposed methods enables genome-wide association analysis and we show with simulation studies that the proposed methods outperform other existing approaches. In particular, we found that the first strategy is always more efficient than the second strategy no matter whether copy numbers for each individual are well identified or not. With the proposed methods, we performed genome-wide CNV association analyses of hematological trait, hematocrit, on 521 Korean family samples. Conclusions We found that statistical analysis with the expected copy number is more powerful than the statistic with the probe intensity measurements regardless of the accuracy of the estimation of copy numbers. Electronic supplementary material The online version of this article (doi:10.1186/s12859-017-1622-z) contains supplementary material, which is available to authorized users.
- Published
- 2017
48. Additional file 1: of On the association analysis of CNV data: a fast and robust family-based association method
- Author
-
Meiling Liu, Sanghoon Moon, Longfei Wang, Sulgi Kim, Yeon-Jung Kim, Hwang, Mi, Kim, Young, Elston, Robert, Bong-Jo Kim, and Sungho Won
- Abstract
A complete report for all experiments performed for this work. Text 1. Rao’s score test statistic with the expected copy number. Text 2. Rao’s score test statistic with the probe intensity measurements. Figure S1. Results of the clustering analysis with family samples (A) and cohort samples (B). Figure S2. Schematic representation of the strategy for the CNV analysis. Figure S3. Validation results. Figure S4. Validation results of replication samples by TaqMan qPCR experiment. Table S1. Specification of parameters for the signal model used in the simulation studies. Table S2. Primer information for CNV validation. Table S3. Accuracy of copy number clusters identified with PedCNV. Table S4. Accuracy of copy number clusters identified with CNVtools. Table S5. Accuracy of copy number estimated with silhouette score. Table S6. Empirical type 1 error estimates when M = 6. Table S7. Empirical power estimates when M = 6. Table S8. Empirical power estimates of T 1 and T 1 * which use the expected copy number and the most probable copy number respectively. Table S9. Estimated parameters of T 1 and T 1 * which use the expected copy number and the most probable copy number respectively. (PDF 814 kb)
- Published
- 2017
- Full Text
- View/download PDF
49. Meta-analysis identifies aMECOMgene as a novel predisposing factor of osteoporotic fracture
- Author
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Joo Yeon Hwang, Ji Young Yun, Lee Jong Young, Min Hye Lee, Myeong Chan Cho, Ho Young Son, Young Ah Kang, Heejo Koo, Hong-Wen Deng, Ghi Su Kim, Shin Yoon Kim, Yoon Shin Cho, Moo Il Kang, Seung Hun Lee, Shiro Ikegawa, Bok Ghee Han, Min Jin Go, Ki Won Oh, Beom-Jun Kim, Soumya Raychaudhuri, My Jung Cha, Sang-Wook Kim, Hye Sook Yoo, Ikuyo Kou, Jung Min Koh, Ji Hee Oh, Dong Joon Kim, Yan Guo, Young Jin Kim, Eun Hee Cho, Youngdoe Kim, and Sanghoon Moon
- Subjects
medicine.medical_specialty ,Genotype ,MECOM ,Quantitative Trait Loci ,Population ,Locus (genetics) ,Genome-wide association study ,Biology ,Bioinformatics ,Polymorphism, Single Nucleotide ,Article ,Osteogenesis ,Molecular genetics ,Proto-Oncogenes ,Genetics ,medicine ,Humans ,Genetic Predisposition to Disease ,education ,Genetics (clinical) ,Aged ,education.field_of_study ,Case-control study ,Middle Aged ,MDS1 and EVI1 Complex Locus Protein ,DNA-Binding Proteins ,Gene Expression Regulation ,Case-Control Studies ,Gene Knockdown Techniques ,Meta-analysis ,Cohort ,Osteoporosis ,Osteoporotic Fractures ,Genome-Wide Association Study ,Transcription Factors - Abstract
Background Osteoporotic fracture (OF) as a clinical endpoint is a major complication of osteoporosis. To screen for OF susceptibility genes, we performed a genome-wide association study and carried out de novo replication analysis of an East Asian population. Methods Association was tested using a logistic regression analysis. A meta-analysis was performed on the combined results using effect size and standard errors estimated for each study. Results In a combined meta-analysis of a discovery cohort (288 cases and 1139 controls), three hospital based sets in replication stage I (462 cases and 1745 controls), and an independent ethnic group in replication stage II (369 cases and 560 for controls), we identified a new locus associated with OF ( rs784288 in the MECOM gene) that showed genome-wide significance (p=3.59×10 −8 ; OR 1.39). RNA interference revealed that a MECOM knockdown suppresses osteoclastogenesis. Conclusions Our findings provide new insights into the genetic architecture underlying OF in East Asians.
- Published
- 2013
50. Genome-wide association studies in the Japanese population identify seven novel loci for type 2 diabetes
- Author
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Danish Saleheen, John Danesh, Claudia H. T. Tam, Josep M. Mercader, Torben Hansen, Sanghoon Moon, Noël P. Burtt, Ivan Brandslund, Rong Zhang, Minaka Iwasaki, Kazuyuki Tobe, Takashi Kadowaki, Daniel R. Witte, Young-Jin Kim, Hiroshi Hirose, Bong-Jo Kim, Jai Rup Singh, Jason Flannick, Hortensia Moreno-Macías, Jun Hosoe, Minako Imamura, Torben Jørgensen, Kazuki Yasuda, Toshimasa Yamauchi, Jose C. Florez, Hirotaka Watada, Richa Saxena, Teresa Tusié-Luna, Atsushi Takahashi, Cramer Christensen, Kyong Soo Park, Juliana C.N. Chan, Niels Grarup, Cheng Hu, Ryuzo Kawamori, Yasushi Tanaka, Asif Rasheed, Kazuo Hara, Kohei Kaku, Ronald C.W. Ma, Jirong Long, Yoon Shin Cho, Dharambir K. Sanghera, E. Shyong Tai, Soo Heon Kwak, Xu Wang, Chikako Ito, Alicia Huerta-Chagoya, Yukinori Okada, Wei Zheng, Wei Zhao, Shiro Maeda, Hayato Fujita, Ken Suzuki, Xiao-Ou Shu, Weiping Jia, Philippe M. Frossard, Oluf Pedersen, Marit E. Jørgensen, Hiroshi Maegawa, Michiaki Kubo, Nobuhiro Shojima, and Minoru Iwata
- Subjects
0301 basic medicine ,Asian Continental Ancestry Group ,Suppressor of Cytokine Signaling Proteins/genetics ,endocrine system diseases ,Science ,Transcription Factors/genetics ,General Physics and Astronomy ,Single-nucleotide polymorphism ,Genome-wide association study ,Suppressor of Cytokine Signaling Proteins ,Biology ,Genetic analysis ,Polymorphism, Single Nucleotide ,General Biochemistry, Genetics and Molecular Biology ,Article ,03 medical and health sciences ,Asian People ,Japan ,Polymorphism (computer science) ,Genotype ,Genetic predisposition ,Humans ,Asian Continental Ancestry Group/genetics ,Genetic Predisposition to Disease ,Genetic association ,Genetics ,Multidisciplinary ,Penicillium ,nutritional and metabolic diseases ,Genomics ,General Chemistry ,Heritability ,3. Good health ,DNA-Binding Proteins ,Genome variation ,030104 developmental biology ,Diabetes Mellitus, Type 2 ,Case-Control Studies ,Diabetes Mellitus, Type 2/genetics ,Genètica ,DNA-Binding Proteins/genetics ,Genome-Wide Association Study ,Transcription Factors - Abstract
Genome-wide association studies (GWAS) have identified more than 80 susceptibility loci for type 2 diabetes (T2D), but most of its heritability still remains to be elucidated. In this study, we conducted a meta-analysis of GWAS for T2D in the Japanese population. Combined data from discovery and subsequent validation analyses (23,399 T2D cases and 31,722 controls) identify 7 new loci with genome-wide significance (P), rs1116357 near CCDC85A, rs147538848 in FAM60A, rs1575972 near DMRTA1, rs9309245 near ASB3, rs67156297 near ATP8B2, rs7107784 near MIR4686 and rs67839313 near INAFM2. Of these, the association of 4 loci with T2D is replicated in multi-ethnic populations other than Japanese (up to 65,936 T2Ds and 158,030 controls, P, 論文
- Published
- 2016
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