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13 results on '"Wu Jer-Yuarn"'

1. Genetic profiles of 103,106 individuals in the Taiwan Biobank provide insights into the health and history of Han Chinese

Author

Wei, Chun-Yu, Yang, Jenn-Hwai, Yeh, Erh-Chan, Tsai, Ming-Fang, Kao, Hsiao-Jung, Lo, Chen-Zen, Chang, Lung-Pao, Lin, Wan-Jia, Hsieh, Feng-Jen, Belsare, Saurabh, Bhaskar, Anand, Su, Ming-Wei, Lee, Te-Chang, Lin, Yi-Ling, Liu, Fu-Tong, Shen, Chen-Yang, Li, Ling-Hui, Chen, Chien-Hsiun, Wall, Jeffrey D, Wu, Jer-Yuarn, and Kwok, Pui-Yan

Subjects
Human Genome, Genetics, Biotechnology, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance, Good Health and Well Being
Abstract

Personalized medical care focuses on prediction of disease risk and response to medications. To build the risk models, access to both large-scale genomic resources and human genetic studies is required. The Taiwan Biobank (TWB) has generated high-coverage, whole-genome sequencing data from 1492 individuals and genome-wide SNP data from 103,106 individuals of Han Chinese ancestry using custom SNP arrays. Principal components analysis of the genotyping data showed that the full range of Han Chinese genetic variation was found in the cohort. The arrays also include thousands of known functional variants, allowing for simultaneous ascertainment of Mendelian disease-causing mutations and variants that affect drug metabolism. We found that 21.2% of the population are mutation carriers of autosomal recessive diseases, 3.1% have mutations in cancer-predisposing genes, and 87.3% carry variants that affect drug response. We highlight how TWB data provide insight into both population history and disease burden, while showing how widespread genetic testing can be used to improve clinical care.

Published
2021

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

Author

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

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Women's Health, Diabetes, Obesity, 2.1 Biological and endogenous factors, Metabolic and endocrine, Aldehyde Dehydrogenase, Mitochondrial, Alleles, Ankyrins, Asian People, Body Mass Index, Case-Control Studies, Diabetes Mellitus, Type 2, Europe, Eye Proteins, Asia, Eastern, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeodomain Proteins, Humans, Male, Nerve Tissue Proteins, RNA, Messenger, Transcription Factors, Transcription, Genetic, Homeobox Protein SIX3, General Science & Technology
Abstract

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Published
2020

3. Towards a reference genome that captures global genetic diversity

Author

Wong, Karen HY, Ma, Walfred, Wei, Chun-Yu, Yeh, Erh-Chan, Lin, Wan-Jia, Wang, Elin HF, Su, Jen-Ping, Hsieh, Feng-Jen, Kao, Hsiao-Jung, Chen, Hsiao-Huei, Chow, Stephen K, Young, Eleanor, Chu, Catherine, Poon, Annie, Yang, Chi-Fan, Lin, Dar-Shong, Hu, Yu-Feng, Wu, Jer-Yuarn, Lee, Ni-Chung, Hwu, Wuh-Liang, Boffelli, Dario, Martin, David, Xiao, Ming, and Kwok, Pui-Yan

Subjects
Biological Sciences, Bioinformatics and Computational Biology, Genetics, Human Genome, Biotechnology, Generic health relevance, Chromosome Mapping, Computational Biology, Gene Expression, Genetic Variation, Genome, Human, Genomics, Genotyping Techniques, Humans, Molecular Sequence Annotation, Population, RNA-Seq, Sequence Analysis, DNA, Transcriptome, Whole Genome Sequencing
Abstract

The current human reference genome is predominantly derived from a single individual and it does not adequately reflect human genetic diversity. Here, we analyze 338 high-quality human assemblies of genetically divergent human populations to identify missing sequences in the human reference genome with breakpoint resolution. We identify 127,727 recurrent non-reference unique insertions spanning 18,048,877 bp, some of which disrupt exons and known regulatory elements. To improve genome annotations, we linearly integrate these sequences into the chromosomal assemblies and construct a Human Diversity Reference. Leveraging this reference, an average of 402,573 previously unmapped reads can be recovered for a given genome sequenced to ~40X coverage. Transcriptomic diversity among these non-reference sequences can also be directly assessed. We successfully map tens of thousands of previously discarded RNA-Seq reads to this reference and identify transcription evidence in 4781 gene loci, underlining the importance of these non-reference sequences in functional genomics. Our extensive datasets are important advances toward a comprehensive reference representation of global human genetic diversity.

Published
2020

4. Association analyses of East Asian individuals and trans-ancestry analyses with European individuals reveal new loci associated with cholesterol and triglyceride levels

Author

Spracklen, Cassandra N, Chen, Peng, Kim, Young Jin, Wang, Xu, Cai, Hui, Li, Shengxu, Long, Jirong, Wu, Ying, Wang, Ya Xing, Takeuchi, Fumihiko, Wu, Jer-Yuarn, Jung, Keum-Ji, Hu, Cheng, Akiyama, Koichi, Zhang, Yonghong, Moon, Sanghoon, Johnson, Todd A, Li, Huaixing, Dorajoo, Rajkumar, He, Meian, Cannon, Maren E, Roman, Tamara S, Salfati, Elias, Lin, Keng-Hung, Guo, Xiuqing, Sheu, Wayne HH, Absher, Devin, Adair, Linda S, Assimes, Themistocles L, Aung, Tin, Cai, Qiuyin, Chang, Li-Ching, Chen, Chien-Hsiun, Chien, Li-Hsin, Chuang, Lee-Ming, Chuang, Shu-Chun, Du, Shufa, Fan, Qiao, Fann, Cathy SJ, Feranil, Alan B, Friedlander, Yechiel, Gordon-Larsen, Penny, Gu, Dongfeng, Gui, Lixuan, Guo, Zhirong, Heng, Chew-Kiat, Hixson, James, Hou, Xuhong, Hsiung, Chao Agnes, Hu, Yao, Hwang, Mi Yeong, Hwu, Chii-Min, Isono, Masato, Juang, Jyh-Ming Jimmy, Khor, Chiea-Chuen, Kim, Yun Kyoung, Koh, Woon-Puay, Kubo, Michiaki, Lee, I-Te, Lee, Sun-Ju, Lee, Wen-Jane, Liang, Kae-Woei, Lim, Blanche, Lim, Sing-Hui, Liu, Jianjun, Nabika, Toru, Pan, Wen-Harn, Peng, Hao, Quertermous, Thomas, Sabanayagam, Charumathi, Sandow, Kevin, Shi, Jinxiu, Sun, Liang, Tan, Pok Chien, Tan, Shu-Pei, Taylor, Kent D, Teo, Yik-Ying, Toh, Sue-Anne, Tsunoda, Tatsuhiko, van Dam, Rob M, Wang, Aili, Wang, Feijie, Wang, Jie, Bin Wei, Wen, Xiang, Yong-Bing, Yao, Jie, Yuan, Jian-Min, Zhang, Rong, Zhao, Wanting, Chen, Yii-Der Ida, Rich, Stephen S, Rotter, Jerome I, Wang, Tzung-Dau, Wu, Tangchun, Lin, Xu, Han, Bok-Ghee, Tanaka, Toshihiro, Cho, Yoon Shin, Katsuya, Tomohiro, and Jia, Weiping

Subjects
Biological Sciences, Genetics, Women's Health, Atherosclerosis, Human Genome, Cardiovascular, Metabolic and endocrine, Stroke, Adult, Alleles, Asian People, Cholesterol, Ethnicity, Female, Gene Frequency, Genetic Association Studies, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Lipids, Lipoproteins, HDL, Lipoproteins, LDL, Male, Middle Aged, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Triglycerides, White People, Medical and Health Sciences, Genetics & Heredity
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

Published
2017

5. Genome-Wide Association Study Meta-Analysis of Long-Term Average Blood Pressure in East Asians

Author

Li, Changwei, Kim, Yun Kyoung, Dorajoo, Rajkumar, Li, Huaixing, Lee, I-Te, Cheng, Ching-Yu, He, Meian, Sheu, Wayne H-H, Guo, Xiuqing, Ganesh, Santhi K, He, Jiang, Lee, Juyoung, Liu, Jianjun, Hu, Yao, Rao, Dabeeru C, Tsai, Fuu-Jen, Koh, Jia Yu, Hu, Hua, Liang, Kae-Woei, Palmas, Walter, Hixson, James E, Han, Sohee, Teo, Yik-Ying, Wang, Yiqin, Chen, Jing, Lu, Chieh Hsiang, Zheng, Yingfeng, Gui, Lixuan, Lee, Wen-Jane, Yao, Jie, Gu, Dongfeng, Han, Bok-Ghee, Sim, Xueling, Sun, Liang, Zhao, Jinying, Chen, Chien-Hsiun, Kumari, Neelam, He, Yunfeng, Taylor, Kent D, Raffel, Leslie J, Moon, Sanghoon, Rotter, Jerome I, Ida Chen, Yii-der, Wu, Tangchun, Wong, Tien Yin, Wu, Jer-Yuarn, Lin, Xu, Tai, E-Shyong, Kim, Bong-Jo, and Kelly, Tanika N

Subjects
Biomedical and Clinical Sciences, Cardiovascular Medicine and Haematology, Genetics, Human Genome, 2.1 Biological and endogenous factors, Cardiovascular, Asian People, Blood Pressure, Asia, Eastern, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Phenotype, Polymorphism, Single Nucleotide, arterial pressure, blood pressure, epidemiology, genome-wide association study, Medical Biotechnology, Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology, Cardiovascular medicine and haematology
Abstract

BackgroundGenome-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 resultsWe 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

Published
2017

6. Genome-wide Trans-ethnic Meta-analysis Identifies Seven Genetic Loci Influencing Erythrocyte Traits and a Role for RBPMS in Erythropoiesis

Author

van Rooij, Frank JA, Qayyum, Rehan, Smith, Albert V, Zhou, Yi, Trompet, Stella, Tanaka, Toshiko, Keller, Margaux F, Chang, Li-Ching, Schmidt, Helena, Yang, Min-Lee, Chen, Ming-Huei, Hayes, James, Johnson, Andrew D, Yanek, Lisa R, Mueller, Christian, Lange, Leslie, Floyd, James S, Ghanbari, Mohsen, Zonderman, Alan B, Jukema, J Wouter, Hofman, Albert, van Duijn, Cornelia M, Desch, Karl C, Saba, Yasaman, Ozel, Ayse B, Snively, Beverly M, Wu, Jer-Yuarn, Schmidt, Reinhold, Fornage, Myriam, Klein, Robert J, Fox, Caroline S, Matsuda, Koichi, Kamatani, Naoyuki, Wild, Philipp S, Stott, David J, Ford, Ian, Slagboom, P Eline, Yang, Jaden, Chu, Audrey Y, Lambert, Amy J, Uitterlinden, André G, Franco, Oscar H, Hofer, Edith, Ginsburg, David, Hu, Bella, Keating, Brendan, Schick, Ursula M, Brody, Jennifer A, Li, Jun Z, Chen, Zhao, Zeller, Tanja, Guralnik, Jack M, Chasman, Daniel I, Peters, Luanne L, Kubo, Michiaki, Becker, Diane M, Li, Jin, Eiriksdottir, Gudny, Rotter, Jerome I, Levy, Daniel, Grossmann, Vera, Patel, Kushang V, Chen, Chien-Hsiun, Project, The BioBank Japan, Ridker, Paul M, Tang, Hua, Launer, Lenore J, Rice, Kenneth M, Li-Gao, Ruifang, Ferrucci, Luigi, Evans, Michelle K, Choudhuri, Avik, Trompouki, Eirini, Abraham, Brian J, Yang, Song, Takahashi, Atsushi, Kamatani, Yoichiro, Kooperberg, Charles, Harris, Tamara B, Jee, Sun Ha, Coresh, Josef, Tsai, Fuu-Jen, Longo, Dan L, Chen, Yuan-Tsong, Felix, Janine F, Yang, Qiong, Psaty, Bruce M, Boerwinkle, Eric, Becker, Lewis C, Mook-Kanamori, Dennis O, Wilson, James G, Gudnason, Vilmundur, O'Donnell, Christopher J, Dehghan, Abbas, Cupples, L Adrienne, Nalls, Michael A, Morris, Andrew P, Okada, Yukinori, Reiner, Alexander P, and Zon, Leonard I

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Hematology, Human Genome, Minority Health, 2.1 Biological and endogenous factors, Africa, Alleles, Animals, Bayes Theorem, Erythrocytes, Erythropoiesis, Ethnicity, Europe, Asia, Eastern, Female, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Male, RNA-Binding Proteins, Racial Groups, Zebrafish, BioBank Japan Project, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genome-wide association studies (GWASs) have identified loci for erythrocyte traits in primarily European ancestry populations. We conducted GWAS meta-analyses of six erythrocyte traits in 71,638 individuals from European, East Asian, and African ancestries using a Bayesian approach to account for heterogeneity in allelic effects and variation in the structure of linkage disequilibrium between ethnicities. We identified seven loci for erythrocyte traits including a locus (RBPMS/GTF2E2) associated with mean corpuscular hemoglobin and mean corpuscular volume. Statistical fine-mapping at this locus pointed to RBPMS at this locus and excluded nearby GTF2E2. Using zebrafish morpholino to evaluate loss of function, we observed a strong in vivo erythropoietic effect for RBPMS but not for GTF2E2, supporting the statistical fine-mapping at this locus and demonstrating that RBPMS is a regulator of erythropoiesis. Our findings show the utility of trans-ethnic GWASs for discovery and characterization of genetic loci influencing hematologic traits.

Published
2017

7. Genetic loci associated with an earlier age at onset in multiplex schizophrenia

Author

Woolston, Annemarie L, Hsiao, Po-Chang, Kuo, Po-Hsiu, Wang, Shi-Heng, Lien, Yin-Ju, Liu, Chih-Min, Hwu, Hai-Gwo, Lu, Tzu-Pin, Chuang, Eric Y, Chang, Li-Ching, Chen, Chien-Hsiun, Wu, Jer-Yuarn, Tsuang, Ming T, and Chen, Wei J

Subjects
Biological Psychology, Biological Sciences, Genetics, Psychology, Brain Disorders, Clinical Research, Schizophrenia, Human Genome, Mental Health, Aging, Aetiology, 2.1 Biological and endogenous factors, Adult, Age of Onset, Aged, Case-Control Studies, Female, Genetic Loci, Genetic Markers, Genetic Predisposition to Disease, Genome-Wide Association Study, Genotype, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, Siblings
Abstract

An earlier age at onset (AAO) has been associated with greater genetic loadings in schizophrenia. This study aimed to identify modifier loci associated with an earlier AAO of schizophrenia. A genome-wide association analysis (GWAS) was conducted in 94 schizophrenia probands with the earliest AAO and 91 with the latest AAO. Candidate single nucleotide polymorphisms (SNPs) were then genotyped in the co-affected siblings and unrelated probands. Multi-SNP genetic risk scores (GRS) composed of the candidate loci were used to distinguish patients with an early or late AAO. The 14-SNP GRS could distinguish the co-affected siblings (n = 90) of the earliest probands from those (n = 91) of the latest probands. When 132 patients with an earlier AAO and 158 patients with a later AAO were included, a significant trend in the 14-SNP GRS was detected among those unrelated probands from 4 family groups with the earliest, earlier, later, and latest AAO. The overall effect of the 14 SNPs on an AAO in schizophrenia was verified using co-affected siblings of the GWAS probands and trend effect across unrelated patients. Preliminary network analysis of these loci revealed the involvement of PARK2, a gene intensively reported in Parkinson's disease and schizophrenia research.

Published
2017

8. Genome-wide association studies in East Asians identify new loci for waist-hip ratio and waist circumference

Author

Wen, Wanqing, Kato, Norihiro, Hwang, Joo-Yeon, Guo, Xingyi, Tabara, Yasuharu, Li, Huaixing, Dorajoo, Rajkumar, Yang, Xiaobo, Tsai, Fuu-Jen, Li, Shengxu, Wu, Ying, Wu, Tangchun, Kim, Soriul, Guo, Xiuqing, Liang, Jun, Shungin, Dmitry, Adair, Linda S, Akiyama, Koichi, Allison, Matthew, Cai, Qiuyin, Chang, Li-Ching, Chen, Chien-Hsiun, Chen, Yuan-Tsong, Cho, Yoon Shin, Choi, Bo Youl, Gao, Yutang, Go, Min Jin, Gu, Dongfeng, Han, Bok-Ghee, He, Meian, Hixson, James E, Hu, Yanling, Huang, Tao, Isono, Masato, Jung, Keum Ji, Kang, Daehee, Kim, Young Jin, Kita, Yoshikuni, Lee, Juyoung, Lee, Nanette R, Lee, Jeannette, Wang, Yiqin, Liu, Jian-Jun, Long, Jirong, Moon, Sanghoon, Nakamura, Yasuyuki, Nakatochi, Masahiro, Ohnaka, Keizo, Rao, Dabeeru, Shi, Jiajun, Sull, Jae Woong, Tan, Aihua, Ueshima, Hirotsugu, Wu, Chen, Xiang, Yong-Bing, Yamamoto, Ken, Yao, Jie, Ye, Xingwang, Yokota, Mitsuhiro, Zhang, Xiaomin, Zheng, Yan, Qi, Lu, Rotter, Jerome I, Jee, Sun Ha, Lin, Dongxin, Mohlke, Karen L, He, Jiang, Mo, Zengnan, Wu, Jer-Yuarn, Tai, E Shyong, Lin, Xu, Miki, Tetsuro, Kim, Bong-Jo, Takeuchi, Fumihiko, Zheng, Wei, and Shu, Xiao-Ou

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Epidemiology, Health Sciences, Obesity, Nutrition, Human Genome, 2.1 Biological and endogenous factors, Oral and gastrointestinal, Cancer, Asia, Asian People, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Polymorphism, Single Nucleotide, Quantitative Trait Loci, Quantitative Trait, Heritable, Sex Factors, Waist Circumference, Waist-Hip Ratio
Abstract

Sixty genetic loci associated with abdominal obesity, measured by waist circumference (WC) and waist-hip ratio (WHR), have been previously identified, primarily from studies conducted in European-ancestry populations. We conducted a meta-analysis of associations of abdominal obesity with approximately 2.5 million single nucleotide polymorphisms (SNPs) among 53,052 (for WC) and 48,312 (for WHR) individuals of Asian descent, and replicated 33 selected SNPs among 3,762 to 17,110 additional individuals. We identified four novel loci near the EFEMP1, ADAMTSL3 , CNPY2, and GNAS genes that were associated with WC after adjustment for body mass index (BMI); two loci near the NID2 and HLA-DRB5 genes associated with WHR after adjustment for BMI, and three loci near the CEP120, TSC22D2, and SLC22A2 genes associated with WC without adjustment for BMI. Functional enrichment analyses revealed enrichment of corticotropin-releasing hormone signaling, GNRH signaling, and/or CDK5 signaling pathways for those newly-identified loci. Our study provides additional insight on genetic contribution to abdominal obesity.

Published
2016

9. Multiple Nonglycemic Genomic Loci Are Newly Associated With Blood Level of Glycated Hemoglobin in East Asians

Author

Chen, Peng, Takeuchi, Fumihiko, Lee, Jong-Young, Li, Huaixing, Wu, Jer-Yuarn, Liang, Jun, Long, Jirong, Tabara, Yasuharu, Goodarzi, Mark O, Pereira, Mark A, Kim, Young Jin, Go, Min Jin, Stram, Daniel O, Vithana, Eranga, Khor, Chiea-Chuen, Liu, Jianjun, Liao, Jiemin, Ye, Xingwang, Wang, Yiqin, Lu, Ling, Young, Terri L, Lee, Jeannette, Thai, Ah Chuan, Cheng, Ching-Yu, van Dam, Rob M, Friedlander, Yechiel, Heng, Chew-Kiat, Koh, Woon-Puay, Chen, Chien-Hsiun, Chang, Li-Ching, Pan, Wen-Harn, Qi, Qibin, Isono, Masato, Zheng, Wei, Cai, Qiuyin, Gao, Yutang, Yamamoto, Ken, Ohnaka, Keizo, Takayanagi, Ryoichi, Kita, Yoshikuni, Ueshima, Hirotsugu, Hsiung, Chao A, Cui, Jinrui, Sheu, Wayne H-H, Rotter, Jerome I, Chen, Yii-Der I, Hsu, Chris, Okada, Yukinori, Kubo, Michiaki, Takahashi, Atsushi, Tanaka, Toshihiro, van Rooij, Frank JA, Ganesh, Santhi K, Huang, Jinyan, Huang, Tao, Yuan, Jianmin, Hwang, Joo-Yeon, Group, CHARGE Hematology Working, Gross, Myron D, Assimes, Themistocles L, Miki, Tetsuro, Shu, Xiao-Ou, Qi, Lu, Chen, Yuan-Tson, Lin, Xu, Aung, Tin, Wong, Tien-Yin, Teo, Yik-Ying, Kim, Bong-Jo, Kato, Norihiro, and Tai, E-Shyong

Subjects
Biomedical and Clinical Sciences, Biotechnology, Prevention, Human Genome, Genetics, Minority Health, Diabetes, 2.1 Biological and endogenous factors, Metabolic and endocrine, Adult, Aged, Asian People, Blood Glucose, Cohort Studies, Asia, Eastern, Female, Genetic Heterogeneity, Genetic Loci, Genome-Wide Association Study, Glycated Hemoglobin, Humans, Male, Middle Aged, Polymorphism, Single Nucleotide, CHARGE Hematology Working Group, Medical and Health Sciences, Endocrinology & Metabolism, Biomedical and clinical sciences
Abstract

Glycated hemoglobin A1c (HbA1c) is used as a measure of glycemic control and also as a diagnostic criterion for diabetes. To discover novel loci harboring common variants associated with HbA1c in East Asians, we conducted a meta-analysis of 13 genome-wide association studies (GWAS; N = 21,026). We replicated our findings in three additional studies comprising 11,576 individuals of East Asian ancestry. Ten variants showed associations that reached genome-wide significance in the discovery data set, of which nine (four novel variants at TMEM79 [P value = 1.3 × 10(-23)], HBS1L/MYB [8.5 × 10(-15)], MYO9B [9.0 × 10(-12)], and CYBA [1.1 × 10(-8)] as well as five variants at loci that had been previously identified [CDKAL1, G6PC2/ABCB11, GCK, ANK1, and FN3KI]) showed consistent evidence of association in replication data sets. These variants explained 1.76% of the variance in HbA1c. Several of these variants (TMEM79, HBS1L/MYB, CYBA, MYO9B, ANK1, and FN3K) showed no association with either blood glucose or type 2 diabetes. Among individuals with nondiabetic levels of fasting glucose (

Published
2014

10. Replication and Meta-Analysis of GWAS Identified Susceptibility Loci in Kawasaki Disease Confirm the Importance of B Lymphoid Tyrosine Kinase (BLK) in Disease Susceptibility

Author

Chang, Chia-Jung, Kuo, Ho-Chang, Chang, Jeng-Sheng, Lee, Jong-Keuk, Tsai, Fuu-Jen, Khor, Chiea Chuen, Chang, Li-Ching, Chen, Shih-Ping, Ko, Tai-Ming, Liu, Yi-Min, Chen, Ying-Ju, Hong, Young Mi, Jang, Gi Young, Hibberd, Martin L, Kuijpers, Taco, Burgner, David, Levin, Michael, Burns, Jane C, Davila, Sonia, Chen, Yuan-Tsong, Chen, Chien-Hsiun, Wu, Jer-Yuarn, and Lee, Yi-Ching

Subjects
Human Genome, Genetics, Prevention, 2.1 Biological and endogenous factors, Aetiology, Asian People, B-Lymphocytes, Cell Line, Transformed, Cohort Studies, Gene Expression Regulation, Enzymologic, Genetic Loci, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Mucocutaneous Lymph Node Syndrome, Polymorphism, Single Nucleotide, Promoter Regions, Genetic, Reproducibility of Results, Republic of Korea, Taiwan, White People, src-Family Kinases, International Kawasaki Disease Genetics Consortium, Korean Kawasaki Disease Genetics Consortium, Taiwan Kawasaki Disease Genetics Consortium, General Science & Technology
Abstract

The BLK and CD40 loci have been associated with Kawasaki disease (KD) in two genome-wide association studies (GWAS) conducted in a Taiwanese population of Han Chinese ancestry (Taiwanese) and in Japanese cohorts. Here we build on these findings with replication studies of the BLK and CD40 loci in populations of Korean and European descent. The BLK region was significantly associated with KD susceptibility in both populations. Within the BLK gene the rs2736340-located linkage disequilibrium (LD ) comprising the promoter and first intron was strongly associated with KD, with the combined results of Asian studies including Taiwanese, Japanese, and Korean populations (2,539 KD patients and 7,021 controls) providing very compelling evidence of association (rs2736340, OR = 1.498, 1.354-1.657; P = 4.74×10(-31)). We determined the percentage of B cells present in the peripheral blood mononuclear cell (PBMC) population and the expression of BLK in the peripheral blood leukocytes (leukocytes) of KD patients during the acute and convalescent stages. The percentage of B cells in the PBMC population and the expression of BLK in leukocytes were induced in patients in the acute stage of KD. In B cell lines derived from KD patients, and in purified B cells from KD patients obtained during the acute stage, those with the risk allele of rs2736340 expressed significantly lower levels of BLK. These results suggest that peripheral B cells play a pathogenic role during the acute stage of KD. Decreased BLK expression in peripheral blood B cells may alter B cell function and predispose individuals to KD. These associative data suggest a role for B cells during acute KD. Understanding the functional implications may facilitate the development of B cell-mediated therapy for KD.

Published
2013

11. Meta-analysis identifies multiple loci associated with kidney function–related traits in east Asian populations

Author

Okada, Yukinori, Sim, Xueling, Go, Min Jin, Wu, Jer-Yuarn, Gu, Dongfeng, Takeuchi, Fumihiko, Takahashi, Atsushi, Maeda, Shiro, Tsunoda, Tatsuhiko, Chen, Peng, Lim, Su-Chi, Wong, Tien-Yin, Liu, Jianjun, Young, Terri L, Aung, Tin, Seielstad, Mark, Teo, Yik-Ying, Kim, Young Jin, Lee, Jong-Young, Han, Bok-Ghee, Kang, Daehee, Chen, Chien-Hsiun, Tsai, Fuu-Jen, Chang, Li-Ching, Fann, S-J Cathy, Mei, Hao, Rao, Dabeeru C, Hixson, James E, Chen, Shufeng, Katsuya, Tomohiro, Isono, Masato, Ogihara, Toshio, Chambers, John C, Zhang, Weihua, Kooner, Jaspal S, Albrecht, Eva, Yamamoto, Kazuhiko, Kubo, Michiaki, Nakamura, Yusuke, Kamatani, Naoyuki, Kato, Norihiro, He, Jiang, Chen, Yuan-Tsong, Cho, Yoon Shin, Tai, E-Shyong, and Tanaka, Toshihiro

Subjects
Biological Sciences, Genetics, Kidney Disease, Human Genome, Renal and urogenital, Asian People, Blood Urea Nitrogen, Cohort Studies, Creatinine, Genetic Predisposition to Disease, Genome-Wide Association Study, Glomerular Filtration Rate, Humans, Kidney, Polymorphism, Single Nucleotide, Renal Insufficiency, Chronic, Uric Acid, KidneyGen Consortium, CKDGen Consortium, GUGC consortium, Medical and Health Sciences, Developmental Biology, Agricultural biotechnology, Bioinformatics and computational biology
Abstract

Chronic kidney disease (CKD), impairment of kidney function, is a serious public health problem, and the assessment of genetic factors influencing kidney function has substantial clinical relevance. Here, we report a meta-analysis of genome-wide association studies for kidney function-related traits, including 71,149 east Asian individuals from 18 studies in 11 population-, hospital- or family-based cohorts, conducted as part of the Asian Genetic Epidemiology Network (AGEN). Our meta-analysis identified 17 loci newly associated with kidney function-related traits, including the concentrations of blood urea nitrogen, uric acid and serum creatinine and estimated glomerular filtration rate based on serum creatinine levels (eGFRcrea) (P < 5.0 × 10(-8)). We further examined these loci with in silico replication in individuals of European ancestry from the KidneyGen, CKDGen and GUGC consortia, including a combined total of ∼110,347 individuals. We identify pleiotropic associations among these loci with kidney function-related traits and risk of CKD. These findings provide new insights into the genetics of kidney function.

Published
2012

12. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

Author

Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E, Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L, Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Zajac, Greg J M, Wu, Kuan-Han H, Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T, Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Havulinna, Aki S, Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A, Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J, Narita, Akira, Takayama, Jun, Martin, Hilary C, Hunt, Karen A, Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Rasheed, Asif, Hindy, George, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R, Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M, Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian'an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A, Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F, Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T, Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E, Bradfield, Jonathan P, Ruotsalainen, Sanni E, Daw, E Warwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Le, Phuong, Feitosa, Mary F, Wojczynski, Mary K, Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Noah, Tsao L, Verma, Anurag, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L, Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J, Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Nongmaithem, Suraj S, Sankareswaran, Alagu, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R H J, Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N, Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C, Wang, Ya Xing, Wei, Wen B, Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A, Banas, Bernhard, Morgan, Anna, Meidtner, Karina, Bielak, Lawrence F, Smith, Jennifer A, Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J, Pitkänen, Niina, Cade, Brian E, van der Laan, Sander W, Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R, Doumatey, Ayo P, Adeyemo, Adebowale A, Lee, Jong Young, Petersen, Eva R B, Nielsen, Aneta A, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W, Wang, Carol A, Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O, van Setten, Jessica, He, Karen Y, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D, Reiner, Alexander P, Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C, Launer, Lenore J, Li, Huaixing, Nalls, Mike A, Raitakari, Olli T, Ichihara, Sahoko, Wild, Sarah H, Nelson, Christopher P, Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S, Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, de Kleijn, Dominique, de Borst, Gert J, Kim, Eung Kweon, Adams, Hieab H H, Ikram, M Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline W J, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Ida Chen, Yii-Der, Pennell, Craig E, Mori, Trevor A, Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M, Stark, Klaus J, Zimmermann, Martina E, Völzke, Henry, Homuth, Georg, Evans, Michele K, Zonderman, Alan B, Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E, Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J, Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A, Kato, Norihiro, Schulze, Matthias B, Girotto, Giorgia, Böger, Carsten A, Jung, Bettina, Joshi, Peter K, Bennett, David A, De Jager, Philip L, Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J, Munroe, Patricia B, Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B, Samani, Nilesh J, Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A, Adair, Linda S, Bechayda, Sonny Augustin, de Silva, H 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Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth J F, Province, Michael A, Parra, Esteban J, Cruz, Miguel, Psaty, Bruce M, Brandslund, Ivan, Pramstaller, Peter P, Rotimi, Charles N, Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F A, Kiemeney, Lambertus, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W, Linneberg, Allan, Jukema, J Wouter, Khera, Amit V, Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O, Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P, Grarup, Niels, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I, Dantoft, Thomas M, Karpe, Fredrik, Neville, Matt J, Timpson, Nicholas J, Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T, Pedersen, Nancy L, Magnusson, Patrik K E, Boomsma, Dorret I, de Geus, Eco J C, Cupples, L Adrienne, van Meurs, Joyce B J, Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C, Kooner, Jaspal S, de Vries, Paul S, Morrison, Alanna C, Hazelhurst, Scott, Ramsay, Michèle, North, Kari E, Daviglus, Martha, Kraft, Peter, Martin, Nicholas G, Whitfield, John B, Abbas, Shahid, Saleheen, Danish, Walters, Robin G, Holmes, Michael V, Black, Corri, Smith, Blair H, Baras, Aris, Justice, Anne E, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A, Trembath, Richard C, Wei, Wei-Qi, Jarvik, Gail P, Namjou, Bahram, Hayes, M Geoffrey, Ritchie, Marylyn D, Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Y Eugene, Ho, Yuk-Lam, Lynch, Julie A, Tsao, Philip S, Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J, Gaziano, John M, Wilson, Peter, Mohlke, Karen L, Frayling, Timothy M, Hirschhorn, Joel N, Kathiresan, Sekar, Boehnke, Michael, Million Veterans Program, Global Lipids Genetics Consortium, Struan Grant, Natarajan, Pradeep, Sun, Yan V, Morris, Andrew P, Deloukas, Panos, Peloso, Gina, Assimes, Themistocles L, Willer, Cristen J, Zhu, Xiang, Brown, Christopher D, Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Tampere University, Clinical Medicine, Department of Clinical Chemistry, TAYS Heart Centre, Department of Clinical Physiology and Nuclear Medicine, Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E, Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L, Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Zajac, Greg J M, Wu, Kuan-Han H, Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T, Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Havulinna, Aki S, Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A, Lingren, Todd, Feng, Qiping, Kullo, Iftikhar J, Narita, Akira, Takayama, Jun, Martin, Hilary C, Hunt, Karen A, Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Rasheed, Asif, Hindy, George, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, Mahajan, Anubha, Brown, Michael R, Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M, Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian'An, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achillea, Hottenga, Jouke Jan, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A, Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agne, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Flori, Mcdaid, Aaron F, Marques-Vidal, Pedro, Wielscher, Matthia, Trompet, Stella, Sattar, Naveed, Møllehave, Line T, Munz, Matthia, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Schönherr, Sebastian, Forer, Luka, Scholz, Marku, Galesloot, Tessel E, Bradfield, Jonathan P, Ruotsalainen, Sanni E, Daw, E Warwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Le, Phuong, Feitosa, Mary F, Wojczynski, Mary K, Hemerich, Daiane, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Noah, Tsao L, Verma, Anurag, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Demirkan, Ayşe, Leonard, Hampton L, Marten, Jonathan, Emmel, Carina, Schmidt, Börge, Smyth, Laura J, Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlo, Lyssenko, Valeriya, Nongmaithem, Suraj S, Sankareswaran, Alagu, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R H J, Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, 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Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M, Stark, Klaus J, Zimmermann, Martina E, Völzke, Henry, Homuth, Georg, Evans, Michele K, Zonderman, Alan B, Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E, Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J, Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Peyser, Patricia A, Kato, Norihiro, Schulze, Matthias B, Girotto, Giorgia, Böger, Carsten A, Jung, Bettina, Joshi, Peter K, Bennett, David A, De Jager, Philip L, Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morri, Caulfield, Mark J, Munroe, Patricia B, Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B, Samani, Nilesh J, Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A, Adair, Linda S, Bechayda, Sonny Augustin, de Silva, H Janaka, Wickremasinghe, Ananda R, Krauss, Ronald M, Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G, Lind, Lar, Heng, Chew-Kiat, Nelson, Amanda E, Golightly, Yvonne M, Wilson, James F, Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J, Rao, D C, Arnett, Donna K, Walker, Mark, Scott, Laura J, Koistinen, Heikki A, Chandak, Giriraj R, Mercader, Josep M, Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E Shyong, van Dam, Rob M, Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F, Mcknight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, Mccarthy, Mark I, Palmer, Colin N A, Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M, Jin, Zi-Bing, Lu, Fan, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, T Hart, Leen M, Elders, Petra J M, Rader, Daniel J, Damrauer, Scott M, Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth J F, Province, Michael A, Parra, Esteban J, Cruz, Miguel, Psaty, Bruce M, Brandslund, Ivan, Pramstaller, Peter P, Rotimi, Charles N, Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F A, Kiemeney, Lambertu, de Graaf, Jacqueline, Loeffler, Marku, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W, Linneberg, Allan, Jukema, J Wouter, Khera, Amit V, Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Francesco, Cucca, Mook-Kanamori, Dennis O, Willems van Dijk, Ko, Watkins, Hugh, Strachan, David P, Grarup, Niel, Sever, Peter, Poulter, Neil, Huey-Herng Sheu, Wayne, Rotter, Jerome I, Dantoft, Thomas M, Karpe, Fredrik, Neville, Matt J, Timpson, Nicholas J, Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T, Pedersen, Nancy L, Magnusson, Patrik K E, Boomsma, Dorret I, de Geus, Eco J C, Cupples, L Adrienne, van Meurs, Joyce B J, Ikram, Arfan, Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, Tuomilehto, Jaakko, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C, Kooner, Jaspal S, de Vries, Paul S, Morrison, Alanna C, Hazelhurst, Scott, Ramsay, Michèle, North, Kari E, Daviglus, Martha, Kraft, Peter, Martin, Nicholas G, Whitfield, John B, Abbas, Shahid, Saleheen, Danish, Walters, Robin G, Holmes, Michael V, Black, Corri, Smith, Blair H, Baras, Ari, Justice, Anne E, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Kooperberg, Charle, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A, Trembath, Richard C, Wei, Wei-Qi, Jarvik, Gail P, Namjou, Bahram, Hayes, M Geoffrey, Ritchie, Marylyn D, Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, Y Eugene, Ho, Yuk-Lam, Lynch, Julie A, Tsao, Philip S, Chang, Kyong-Mi, Cho, Kelly, O'Donnell, Christopher J, Gaziano, John M, Wilson, Peter, Mohlke, Karen L, Frayling, Timothy M, Hirschhorn, Joel N, Kathiresan, Sekar, Boehnke, Michael, Struan Grant, Null, Natarajan, Pradeep, Sun, Yan V, Morris, Andrew P, Deloukas, Pano, Peloso, Gina, Assimes, Themistocles L, Willer, Cristen J, Zhu, Xiang, Brown, Christopher D, Epidemiology and Data Science, ACS - Diabetes & metabolism, ACS - Heart failure & arrhythmias, APH - Health Behaviors & Chronic Diseases, Psychiatry, APH - Mental Health, Amsterdam Neuroscience - Complex Trait Genetics, Amsterdam Neuroscience - Mood, Anxiety, Psychosis, Stress & Sleep, General practice, APH - Aging & Later Life, APH - Digital Health, Million Veterans Program, Global Lipids Genetics Consortium, Radiology & Nuclear Medicine, Internal Medicine, Epidemiology, Biological Psychology, APH - Personalized Medicine, APH - Methodology, AMS - Ageing & Vitality, and AMS - Sports

Subjects
regulatory mechanism, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], post-GWAS, Medizin, complex traits, fine-mapping, functional genomics, lipid biology, variant prioritization, Medical and Health Sciences, Polymorphism, Single Nucleotide, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Article, INTEGRATIVE ANALYSIS, WIDE ASSOCIATION, 3D GENOME, VARIANTS, CHOLESTEROL, ANNOTATION, OBESITY, COMMON, LOCI, EXPRESSION, functional genomic, Genetics, 2.1 Biological and endogenous factors, Humans, Genetics(clinical), Polymorphism, Aetiology, Genetics (clinical), Genetics & Heredity, Chromatin/genetics, Genome-Wide Association Study, Genomics, Lipids/genetics, Polymorphism, Single Nucleotide/genetics, Human Genome, Million Veterans Program, Global Lipids Genetics Consortium, Single Nucleotide, Biological Sciences, Lipids, Chromatin, complex trait, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], 3111 Biomedicine, Biotechnology
Abstract

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology. Xiang Zhu is supported by the Stein Fellowship from Stanford University and Institute for Computational and Data Sciences Seed Grant from The Pennsylvania State University. C.D.B. is supported by the NIH (R01-HL133218). Funding for the Global Lipids Genetics Consortium was provided by the NIH (R01-HL127564). This research was conducted using the UK Biobank Resource under application number 24460. This research is based on data from the Million Veteran Program, Office of Research and Development, Veterans Health Administration, and was supported by awards 2I01BX003362-03A1 and 1I01BX004821-01A1. This publication does not represent the views of the Department of Veteran Affairs or the United States Government. We thank Bethany Klunder for administrative support. Study-specific acknowledgments are provided in the supplemental information.

Published
2022
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13. A genome-wide survey of copy number variations in Han Chinese residing in Taiwan

Author

Lin, Chien-Hsing, Lin, Ying-Chao, Wu, Jer-Yuarn, Pan, Wen-Harn, Chen, Yuan-Tsong, and Fann, Cathy S.J.

Subjects
*HUMAN genome, *NUCLEOTIDE sequence, *GENETIC code, *DNA microarrays, *GENETIC polymorphisms, *CHINESE people, *BIOCHIPS
Abstract

Abstract: Copy number variation (CNV) is a form of DNA sequence variation in the human genome. CNVs can affect expression of nearby and distant genes, and some of them might cause certain phenotypic differences. CNVs vary slightly in location and frequency among different populations. Because currently-available CNV information from Asian population was limited to fewer small-scale studies with only dozens of subjects, a high-resolution CNV survey was conducted using a large number of Han Chinese in this study. The Illumina HumanMap550K single-nucleotide polymorphism array was used to identify CNVs from 813 unrelated Han Chinese residing in Taiwan. A total of 365 CNV regions were identified in this population, and the average size of the CNV regions was 235 kb (covering a total of 2.86% of the human genome), and 67 (18.4%) were newly-discovered CNV regions. Two hundred and seventy-nine CNV regions (76%) were verified from 304 randomly-selected samples by Affymetrix 500K GeneChip and qPCR experiments. These regions contain 1029 genes, some of which are associated with diseases. Consistent with previous studies, most CNVs were rare structural variations in the human genome, and only 64 regions (17.5%) had a CNV allele frequency greater than 1%. Our discovery of 67 new CNV regions indicates that previous CNV coverage of the human genome is incomplete and there is diversity among different ethnic populations. The comprehensive knowledge of CNVs in the human genome is very important and useful in further genetic studies. [Copyright &y& Elsevier]

Published
2009
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