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16 results on '"Bok-Ghee Han"'

1. Identification of FAM13A gene associated with the ratio of FEV1 to FVC in Korean population by genome-wide association studies including gene–environment interactions

Author

Sun Ha Jee, Jae Woong Sull, Soriul Kim, Hyun Kim, Namhan Cho, Bok Ghee Han, Chol Shin, and Seung Ku Lee

Subjects
Adult, Vital Capacity, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Pulmonary function testing, Cohort Studies, Pulmonary Disease, Chronic Obstructive, FEV1/FVC ratio, Asian People, Gene Frequency, Risk Factors, Forced Expiratory Volume, Republic of Korea, Genetics, medicine, Humans, Genetic Predisposition to Disease, Risk factor, Genetics (clinical), COPD, Base Sequence, GTPase-Activating Proteins, Smoking, Haplotype, Middle Aged, medicine.disease, respiratory tract diseases, Haplotypes, Genetic epidemiology, Multivariate Analysis, Cohort, Linear Models, Gene-Environment Interaction, Genome-Wide Association Study
Abstract

Chronic obstructive pulmonary disease (COPD) is a complex, multifactorial disease. Although smoking is a main risk factor for obstructive impairment, not all smokers develop this critical disease. We conducted a genome-wide association study to identify the association between genetic variants and pulmonary function and also examined how these variants relate to lung impairment in accordance with smoking behaviors. Using two community-based cohorts, the Ansan cohort (n=4319) and the Ansung cohort (n=3674), in the Korean Genome Epidemiology Study, we analyzed the association between genetic variants (single-nucleotide polymorphisms and haplotypes) and the ratio of FEV1 to FVC (FEV1/FVC) using multivariate linear regression models. Similar analyses were conducted after stratification by smoking status. Four genome-wide significant signals in the FAM13A gene (the strongest signal at rs2609264, P=1.76 × 10(-7) in a combined set) were associated with FEV1/FVC. For the association with ratio, the effect size in the CTGA haplotype (risk haplotype) was -0.57% (s.e., 0.11; P=2.10 × 10(-7)) as compared with the TCAG haplotype (reference haplotype) in a combined set. There was also a significant interaction of FAM13A haplotypes with heavy smoking on FEV1/FVC (P for interaction=0.028). We confirmed the previously reported association of FAM13A in 4q22.1 with pulmonary function. The FAM13A haplotypes also interacted with heavy smoking to affect the risk of reduced pulmonary function.

Published
2015

2. Genome-wide trans-ancestry meta-analysis provides insight into the genetic architecture of type 2 diabetes susceptibility

Author

Tazeen H. Jafar, Lars Lind, Peter Almgren, Wendy Winckler, Eitaro Nakashima, Young Min Cho, Annette Peters, Rona J. Strawbridge, Ananda R. Wickremasinghe, Katharine R. Owen, Lee-Ming Chuang, Tien-Jyun Chang, Graeme I. Bell, James B. Meigs, Bill Musk, Timo A. Lakka, Elin Grundberg, Wei Lu, Sarah Edkins, George Dedoussis, Weiping Jia, Danish Saleheen, Suthesh Sivapalaratnam, Maria Samuel, Tien Yin Wong, Lu Qi, Pierre Fontanillas, Momoko Horikoshi, Jirong Long, Abdul Basit, Anubha Mahajan, Andrew T. Hattersley, Markus M. Nöthen, Denis Rybin, Inger Njølstad, S. Krithika, Miguel Cruz, Delilah Zabaneh, Leena Peltonen, Jasmina Kravic, Sangsoo Kim, David Couper, Lori L. Bonnycastle, Heather M. Stringham, Yi-Cheng Chang, Paul Elliott, Eric J.G. Sijbrands, Nita G. Forouhi, Alena Stančáková, Ghazala Mirza, Robert W. Lawrence, Ruth J. F. Loos, Norman Klopp, Shiro Maeda, Martina Müller-Nurasyid, Jer-Yuarn Wu, Jianjun Liu, Kee Seng Chia, Elodie Eury, Loukianos S. Rallidis, Timothy M. Frayling, Ken Yamamoto, David Altshuler, Gunnar Sigurosson, Harald Grallert, Jackie F. Price, Barbara Thorand, Jouko Saramies, Malene M. Kristensen, Sonali Pechlivanis, Inês Barroso, Jong-Young Lee, Melissa Parkin, Josée Dupuis, Stéphane Lobbens, Jesús Kumate, Elena Tremoli, Sudhir Kowlessur, Xueling Sim, Norihiro Kato, Philippe Froguel, Kathleen Stirrups, Eero Lindholm, Alex S. F. Doney, Andres Metspalu, Yu-Tang Gao, Roman Wennauer, Xiao-Ou Shu, Marilyn C. Cornelis, Veikko Salomaa, Nanette R. Lee, Johanna Kuusisto, Caroline S. Fox, Man Li, James Scott, Wing-Yee So, Andrew R. Wood, Inga Prokopenko, Oddgeir L. Holmen, Tin Aung, Ryoichi Takayanagi, Chen Suo, Hara Kazuo, Carl G. P. Platou, Ann M. Kelly, Teresa Ferreira, Karl-Heinz Jöckel, Wei-Yen Lim, James F. Wilson, Tom Forsén, Qi Sun, Valur Emilsson, Gonçalo R. Abecasis, Fan Zhang, Timo Saaristo, Harry Campbell, Ying Wu, Mark Seielstad, Wei Zheng, Han Chen, Stavroula Kanoni, Yuqian Bao, Jose C. Florez, Wan Ting Tay, Ronald C. WMa, Gerald Steinbach, Min Jin Go, Rong Zhang, Junbin Liang, Vasiliki Lagou, Leif Groop, Emil Rehnberg, Nabi Shah, Weihua Zhang, Yun Li, Bengt Sennblad, Olle Melander, Nancy L. Pedersen, Muhammed Islam, Jaakko Tuomilehto, Young Jin Kim, Richard N. Bergman, Juliana C.N. Chan, Eleftheria Zeggini, Andrew D. Johnson, Kees Hovingh, Joban Sehmi, Rainer Rauramaa, Satu Männistö, Reedik Mägi, Samuel Liju, Mingyu Yang, Ayellet V. Segrè, Noël P. Burtt, Mozhgan Dorkhan, Beverley Balkau, Neelam Hassanali, Hyun Min Kang, Fabrizio Veglia, Eeva Korpi-Hyövälti, Loic Yengo, Elizabeth J. Rossin, Angela Silveira, Maggie C.Y. Ng, Yuan-Tsong Chen, Anders Hamsten, David R. Matthews, Mark J. Caulfield, Emmi Tikkanen, Tanya M. Teslovich, John R. B. Perry, Karen L. Mohlke, Sarah E. Hunt, Soo Heon Kwak, Jorge Escobedo, Christopher J. Groves, Ulf de Faire, Jeremy B M Jowett, Gudmar Thorleifsson, Michael Roden, Evelin Mihailov, Viswanathan Mohan, Craig L. Hanis, Thomas WMühleisen, Congrong Wang, Sonia Shah, Kyle J. Gaulton, Jaspal S. Kooner, Jiro Nakamura, Mustafa Atalay, Linda S. Adair, S Wiltshire, Tõnu Esko, Anna Jonsson, Antigone S. Dimas, Karin Leander, Li Ching Chang, George B. Grant, Bo Isomaa, Anne U. Jackson, Claudia Langenberg, Kristian Hveem, Yoon Shin Cho, Astradur B. Hreidarsson, Xu Wang, Keizo Ohnaka, Alexandra C. Nica, Simon D. Rees, Pau Navarro, Sekar Kathiresan, Rob M. van Dam, Zafar I. Hydrie, Bok Ghee Han, Francis S. Collins, Fuu Jen Tsai, Unnur Thorsteinsdottir, Ross M. Fraser, Caroline Hayward, Cornelia M. van Duijn, Samuli Ripatti, Mieke D. Trip, Hyung Lae Kim, Rafn Benediktsson, Candace Guiducci, Bruna Gigante, Kyong Soo Park, Wen Hong L. Kao, Tom Wilsgaard, Leena Kinnunen, John Danesh, Alan James, Alan R. Shuldiner, Mitsuhiro Yokota, Jen Mai Lee, Kari Stefansson, Erik Ingelsson, Colin N. A. Palmer, David J. Hunter, Paul Zimmet, Manickam Chidambaram, Sirkka Keinänen-Kiukaanniemi, Laura J. Scott, Susanne Moebus, Benjamin F. Voight, Wolfgang Rathmann, Hassan Khan, Thomas Illig, Prasad Katulanda, Christian Gieger, Andrew D. Morris, Yik Ying Teo, Andrew P. Morris, Venkatesan Radha, N. William Rayner, Johan G. Eriksson, Christian Dina, Igor Rudan, Sailaja Vedantam, Cheng Hu, James S. Pankow, Ann-Christine Syvänen, Karl Gertow, Valeriya Lyssenko, Guillaume Charpentier, Albert Hofman, Chiea Chuen Khor, Joseph Trakalo, Peter Kraft, Takashi Kadowaki, Qiuyin Cai, John C. Chambers, André G. Uitterlinden, Simon C. Potter, Nicholas J. Wareham, Soumya Raychaudhuri, Jian'an Luan, Tiinamaija Tuomi, Anthony H. Barnett, Juha Saltevo, Robert A. Scott, Valgerdur Steinthorsdottir, Peng Keat Ng, Mark I. McCarthy, Åsa K. Hedman, Kerrin S. Small, Julia Meyer, Frank B. Hu, Cecilia M. Lindgren, Jennifer E. Below, Nancy J. Cox, Jennie Hui, Andrew Crenshaw, Latonya F. Been, Nam H. Cho, Janani Pinidiyapathirage, A. Samad Shera, Bernhard OBoehm, Jason Carey, Augustine Kong, Twee Hee Ong, Philippe M. Frossard, Donald W. Bowden, Toshimasa Yamauchi, Steve E. Humphries, Cordelia Langford, Xinzhong Li, Hiroshi Ikegami, Stéphane Cauchi, Ching-Ti Liu, Michael Boehnke, Peter M. Nilsson, Debashish Das, John Beilby, Robin Young, Christian Herder, Asif Rasheed, Neil Robertson, Raimund Erbel, Fumihiko Takeuchi, Markku Laakso, Esteban J. Parra, Panos Deloukas, Eric Boerwinkle, Adan Valladares-Salgado, Chien-Hsiun Chen, Kay-Tee Khaw, Damiano Baldassarre, Ashok Kumar, E. Shyong Tai, Peter S. 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Sch Med, Singapore 639798, Singapore [ 41 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 42 ] Baylor Coll Med, Human Genome Sequencing Ctr, Houston, TX 77030 USA [ 43 ] NHGRI, NIH, Bethesda, MD 20892 USA [ 44 ] Broad Inst Harvard & Massachusetts Inst Technol M, Cambridge, MA USA [ 45 ] Vanderbilt Univ, Sch Med, Vanderbilt Ingram Canc Ctr, Vanderbilt Epidemiol Ctr,Dept Med, Nashville, TN 37212 USA [ 46 ] Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh, Midlothian, Scotland [ 47 ] Univ Edinburgh, Western Gen Hosp, MRC, Inst Genet & Mol Med, Edinburgh, Midlothian, Scotland [ 48 ] CNRS, Unite Mixte Rech UMR 8199, Inst Biol, Lille, France [ 49 ] Univ Lille 2, Inst Pasteur, Lille, France [ 50 ] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, London, England [ 51 ] Queen Mary Univ London, Barts & London Sch Med, William Harvey Res Inst, Barts & London Genome Ctr, London, England [ 52 ] Chinese Univ Hong Kong, Prince Wales Hosp, Dept Med & Therapeut, Hong Kong, Hong Kong, Peoples R China [ 53 ] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan [ 54 ] Natl Taiwan Univ Hosp, Dept Internal Med, Taipei 100, Taiwan [ 55 ] Corbeil Essonnes Hosp, Endocrinol Diabetol Unit, Corbeil Essonnes, France [ 56 ] China Med Univ, Sch Chinese Med, Taichung, Taiwan [ 57 ] Boston Univ, Sch Publ Hlth, Dept Biostat, Boston, MA USA [ 58 ] Natl Univ Singapore, Ctr Mol Epidemiol, Singapore 117548, Singapore [ 59 ] Indian Council Med Res, Adv Ctr Genom Diabet, Madras Diabet Res Fdn, Dept Mol Genet, Madras, Tamil Nadu, India [ 60 ] Ajou Univ, Sch Med, Dept Prevent Med, Suwon 441749, South Korea [ 61 ] Seoul Natl Univ, Coll Med, Dept Internal Med, Seoul 151, South Korea [ 62 ] Natl Taiwan Univ, Sch Med, Grad Inst Clin Med, Taipei 10764, Taiwan [ 63 ] Harvard Univ, Sch Publ Hlth, Dept Nutr & Epidemiol, Boston, MA 02115 USA [ 64 ] Univ N Carolina, Dept Biostat, Collaborat Studies Coordinating Ctr, Chapel Hill, NC USA [ 65 ] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore [ 66 ] Ealing Hosp NHS Trust, Southall, Middx, England [ 67 ] Karolinska Inst, Inst Environm Med, Divis Cardiovasc Epidemiol, S-10401 Stockholm, Sweden [ 68 ] Harokopio Univ, Dept Dietet Nutr, Athens, Greece [ 69 ] Univ Geneva, Sch Med, Dept Genet Med & Dev, CH-1211 Geneva, Switzerland [ 70 ] Biomed Sci Res Ctr Alexander Fleming, Vari, Greece [ 71 ] INSERM, UMR 1087, Nantes, France [ 72 ] CNRS, UMR 6291, Nantes, France [ 73 ] Univ Nantes, Nantes, France [ 74 ] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Diabet Res Ctr, Dundee, Scotland [ 75 ] Univ Dundee, Ninewells Hosp, Biomed Res Inst, Pharmacogen Ctr, Dundee, Scotland [ 76 ] Univ Oxford, Dept Stat, Oxford OX1 3TG, England [ 77 ] Erasmus Univ, Med Ctr, Dept Epidemiol, Rotterdam, Netherlands [ 78 ] Netherlands Consortium Healthy Ageing, Netherland Genom Initiat, Rotterdam, Netherlands [ 79 ] Ctr Med Syst Biol, Rotterdam, Netherlands [ 80 ] Univ London Imperial Coll Sci Technol & Med, MRC, Hlth Protect Agcy, Ctr Environm & Hlth, London, England [ 81 ] Iceland Heart Assoc, Kopavogur, Iceland [ 82 ] Univ Duisburg Essen, Univ Hosp Essen, West German Heart Ctr, Clin Cardiol, Essen, Germany [ 83 ] Natl Inst Hlth & Welf, Dept Chron Dis Prevent, Helsinki, Finland [ 84 ] Univ Helsinki, Dept Gen Practice & Primary Hlth Care, Helsinki, Finland [ 85 ] Univ Helsinki, Gen Hosp, Unit Gen Practice, Helsinki, Finland [ 86 ] Folkhalsan Res Ctr, Helsinki, Finland [ 87 ] Inst Mexicano Seguro Social, Hosp Gen Reg 1, Unidad Invest Epidemiol Clin, Mexico City, DF, Mexico [ 88 ] Univ Tartu, Estonian Genome Ctr, EE-50090 Tartu, Estonia [ 89 ] Univ Tartu, Inst Mol & Cell Biol, EE-50090 Tartu, Estonia [ 90 ] Broad Inst, Program Med & Populat Genet, Cambridge, MA USA [ 91 ] Childrens Hosp, Div Genet & Endocrinol, Boston, MA 02115 USA [ 92 ] Harvard Univ, Sch Med, Dept Med, Boston, MA USA [ 93 ] Massachusetts Gen Hosp, Ctr Human Genet Res, Boston, MA 02114 USA [ 94 ] Massachusetts Gen Hosp, Diabet Res Ctr, Diabet Unit, Boston, MA 02114 USA [ 95 ] Addenbrookes Hosp, Inst Metab Sci, MRC, Epidemiol Unit, Cambridge, England [ 96 ] Vaasa Hlth Care Ctr, Vaasa, Finland [ 97 ] Brigham & Womens Hosp, Div Endocrinol & Metab, Boston, MA 02115 USA [ 98 ] Harvard Univ, Sch Med, Boston, MA USA [ 99 ] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England [ 100 ] Shanghai Canc Inst, Dept Epidemiol, Shanghai, Peoples R China [ 101 ] Karolinska Inst, Dept Med Solna, Atherosclerosis Res Unit, Stockholm, Sweden [ 102 ] Karolinska Univ, Hosp Solna, Ctr Mol Med, Stockholm, Sweden [ 103 ] Helmholtz Zentrum Muenchen, Inst Genet Epidemiol, Neuherberg, Germany [ 104 ] Helmholtz Zentrum Muenchen, Res Unit Mol Epidemiol, Neuherberg, Germany [ 105 ] Univ Munich, Clin Cooperat Grp Diabet, Munich, Germany [ 106 ] Helmholtz Zentrum Muenchen, Munich, Germany [ 107 ] Tech Univ Munich, Clin Cooperat Grp Nutrigen & Type Diabet 2, Munich, Germany [ 108 ] German Ctr Diabet Res DZD, Neuherberg, Germany [ 109 ] Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England [ 110 ] Univ Tokyo, Grad Sch Med, Dept Diabet & Metab Dis, Tokyo, Japan [ 111 ] Univ Exeter, Peninsula Med Sch, Inst Biomed & Clin Sci, Exeter, Devon, England [ 112 ] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Clin Diabetol, Dusseldorf, Germany [ 113 ] Norwegian Univ Sci & Technol, Dept Publ Hlth & Gen Practice, HUNT Res Ctr, Levanger, Norway [ 114 ] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands [ 115 ] Brigham & Womens Hosp, Dept Med, Channing Lab, Boston, MA USA [ 116 ] Univ Western Australia, Sch Populat Hlth, Nedlands, WA 6009, Australia [ 117 ] UCL, Inst Cardiovasc Sci, London, England [ 118 ] Harvard Univ, Sch Publ Hlth, Program Mol & Genet Epidemiol, Boston, MA 02115 USA [ 119 ] Kinki Univ, Sch Med, Dept Diabet Endocrinol & Metab, Osaka 589, Japan [ 120 ] Hannover Med Sch, Hannover Unified Biobank, Hannover, Germany [ 121 ] Univ Uppsala Hosp, Dept Mol Sci, Mol Epidemiol & Sci Life Lab, Uppsala, Sweden [ 122 ] Aga Khan Univ, Dept Community Hlth Sci, Karachi, Pakistan [ 123 ] Dept Social Serv & Hlth Care, Pietarsaari, Finland [ 124 ] Aga Khan Univ, Dept Med, Karachi, Pakistan [ 125 ] Queen Elizabeth II Med Ctr, West Australian Sleep Disorders Res Inst, Dept Pulm Physiol & Sleep Med, Nedlands, WA, Australia [ 126 ] Univ Western Australia, Sch Med & Pharmacol, Nedlands, WA 6009, Australia [ 127 ] Univ Hosp Essen, Inst Med Informat Biometry & Epidemiol, Essen, Germany [ 128 ] Heart & Diabet Inst, Baker Int Diabet Inst IDI, Melbourne, Australia [ 129 ] Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA [ 130 ] Massachusetts Gen Hosp, Cardiovasc Res Ctr, Boston, MA 02114 USA [ 131 ] Natl Ctr Global Hlth & Med, Res Inst, Shinjuku Ku, Tokyo, Japan [ 132 ] Univ Colombo, Dept Clin Med, Diabet Res Unit, Colombo, Sri Lanka [ 133 ] Univ Oulu, Inst Hlth Sci, Fac Med, Oulu, Finland [ 134 ] Oulu Univ Hosp, Unit Gen Practice, Oulu, Finland [ 135 ] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore [ 136 ] Ewha Womans Univ, Sch Med, Dept Biochem, Seoul, South Korea [ 137 ] Soongsil Univ, Sch Syst Biomed Sci, Seoul, South Korea [ 138 ] Natl Inst Hlth & Welf, Diabet Prevent Unit, Helsinki, Finland [ 139 ] deCODE Genet, Reykjavik, Iceland [ 140 ] South Ostrobothnia Cent Hosp, Seinajoki, Finland [ 141 ] Minist Hlth, Port Louis, Mauritius [ 142 ] Univ Toronto, Dept Anthropol, Mississauga, ON L5L 1C6, Canada [ 143 ] Fdn IMSS, Mexico City, DF, Mexico [ 144 ] Univ Eastern Finland, Dept Med, Kuopio, Finland [ 145 ] Kuopio Univ Hosp, SF-70210 Kuopio, Finland [ 146 ] Kuopio Res Inst Exercise Med, Kuopio, Finland [ 147 ] Univ Western Australia, Ctr Genet Epidemiol & Biostat, Nedlands, WA 6009, Australia [ 148 ] Univ San Carlos, Off Populat Studies Fdn Inc, Cebu, Philippines [ 149 ] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Natl Heart & Lung Inst, London, England [ 150 ] Univ N Carolina, Dept Genet, Chapel Hill, NC USA [ 151 ] Univ N Carolina, Dept Biostat, Chapel Hill, NC USA [ 152 ] Beijing Genom Inst, Shenzhen, Peoples R China [ 153 ] Uppsala Univ, Akad Sjukhuset, Dept Med Sci, Uppsala, Sweden [ 154 ] Mt Sinai Sch Med, Charles R Bronfman Inst Personalized Med, New York, NY USA [ 155 ] Mt Sinai Sch Med, Child Hlth & Dev Inst, New York, NY USA [ 156 ] Mt Sinai Sch Med, Dept Prevent Med, New York, NY USA [ 157 ] Shanghai Inst Prevent Med, Shanghai, Peoples R China [ 158 ] Massachusetts Gen Hosp, Div Gen Med, Boston, MA 02114 USA [ 159 ] Dr Mohans Diabet Specialties Ctr, Madras, Tamil Nadu, India [ 160 ] Univ Bonn, Inst Human Genet, Bonn, Germany [ 161 ] Univ Bonn, Life & Brain Ctr, Dept Genom, Bonn, Germany [ 162 ] Univ Munich, Chair Genet Epidemiol, Inst Med Informat Biometry & Epidemiol, Munich, Germany [ 163 ] Univ Munich, Univ Hosp Grosshadern, Dept Med 1, Munich, Germany [ 164 ] Sir Charles Gairdner Hosp, Nedlands, WA 6009, Australia [ 165 ] Nagoya Univ, Grad Sch Med, Div Endocrinol & Diabet, Dept Internal Med, Nagoya, Aichi 4648601, Japan [ 166 ] Chubu Rosai Hosp, Dept Endocrinol & Diabet, Nagoya, Aichi, Japan [ 167 ] Univ Tromso, Fac Hlth Sci, Dept Community Med, Tromso, Norway [ 168 ] Kyushu Univ, Grad Sch Med Sci, Dept Geriatr Med, Higashi Ku, Fukuoka 812, Japan [ 169 ] Churchill Hosp, Hlth Res Biomed Res Ctr, Oxford Natl Inst, Oxford OX3 7LJ, England [ 170 ] Univ Minnesota, Div Epidemiol & Community Hlth, Minneapolis, MN USA [ 171 ] Seoul Natl Univ, Grad Sch Convergence Sci & Technol, Dept Mol Med & Biopharmaceut Sci, World Class Univ Program, Seoul, South Korea [ 172 ] Seoul Natl Univ, Coll Med, Seoul, South Korea [ 173 ] Karolinska Inst, Dept Med Epidemiol & Biostat, Stockholm, Sweden [ 174 ] Inst Mol Med Finland FIMM, Helsinki, Finland [ 175 ] Helmholtz Zentrum Muenchen, Inst Epidemiol 2, Neuherberg, Germany [ 176 ] Univ Kelaniya, Fac Med, Dept Publ Hlth, Ragama, Sri Lanka [ 177 ] Nord Trondelag Hlth Trust, Levanger Hosp, Dept Internal Med, Levanger, Norway [ 178 ] Univ Gen Hosp Attikon, Athens, Greece [ 179 ] Univ Dusseldorf, Leibniz Ctr Diabet Res, German Diabet Ctr, Inst Biometr & Epidemiol, Dusseldorf, Germany [ 180 ] Kuopio Univ Hosp, Dept Clin Physiol & Nucl Med, SF-70210 Kuopio, Finland [ 181 ] Harvard Univ, Brigham & Womens Hosp, Sch Med, Div Rheumatol Immunol & Allergy, Boston, MA 02115 USA [ 182 ] Partners Ctr Personalized Genom Med, Boston, MA USA [ 183 ] Univ Dusseldorf, Dept Endocrinol & Diabetol, Dusseldorf, Germany [ 184 ] Univ Dusseldorf, Dept Metab Dis, Dusseldorf, Germany [ 185 ] Harvard Univ, Hlth Sci & Technol MD Program, Boston, MA 02115 USA [ 186 ] MIT, Boston, MA USA [ 187 ] Harvard Univ, Harvard Biol & Biomed Sci Program, Boston, MA 02115 USA [ 188 ] Boston Univ, Data Coordinating Ctr, Boston, MA 02215 USA [ 189 ] Finnish Diabet Assoc, Tampere, Finland [ 190 ] Pirkanmaa Hosp Dist, Tampere, Finland [ 191 ] Cent Finland Cent Hosp, Dept Med, Jyvaskyla, Finland [ 192 ] South Karelia Cent Hosp, Lappeenranta, Finland [ 193 ] UCL, Dept Genet Evolut & Environm, Genet Inst, London, England [ 194 ] Diabet Assoc Pakistan, Karachi, Pakistan [ 195 ] Univ Maryland, Sch Med, Div Endocrinol Diabet & Nutr, Baltimore, MD 21201 USA [ 196 ] Baltimore Vet Adm Med Ctr, Geriatr Res Educ & Clin Ctr, Baltimore, MD USA [ 197 ] Univ Maryland, Sch Med, Program Personalised & Genom Med, Baltimore, MD 21201 USA [ 198 ] Erasmus Univ, Med Ctr, Dept Internal Med, Rotterdam, Netherlands [ 199 ] Univ Ulm, Dept Clin Chem, D-89069 Ulm, Germany [ 200 ] Univ Ulm, Cent Lab, D-89069 Ulm, Germany [ 201 ] Uppsala Univ, Dept Med Sci, Uppsala, Sweden [ 202 ] Kyushu Univ, Grad Sch Med Sci, Dept Internal Med & Bioregulatory Sci, Higashi Ku, Fukuoka 812, Japan [ 203 ] Univ Helsinki, Helsinki Univ Hosp, Dept Med, Helsinki, Finland [ 204 ] Hosp Univ LaPaz IdiPAZ, Inst Invest Sanitaria, Madrid, Spain [ 205 ] Danube Univ Krems, Ctr Vasc Prevent, Krems, Austria [ 206 ] King Abdulaziz Univ, Diabet Res Grp, Jeddah 21413, Saudi Arabia [ 207 ] IMSS, Ctr Med Nacl Siglo 21, Hosp Especialidades, Unidad Invest Med Bioquim, Mexico City, DF, Mexico [ 208 ] Univ Penn, Perelman Sch Med, Dept Pharmacol, Philadelphia, PA 19104 USA [ 209 ] Univ Melbourne, Ctr Eye Res Australia, East Melbourne, Vic, Australia [ 210 ] Kyushu Univ, Med Inst Bioregulat, Res Ctr Genet Informat, Div Genome Anal,Higashi Ku, Fukuoka 812, Japan [ 211 ] Univ Lille 1, Math Lab, CNRS UMR 8524, MODAL Team,INRIA Lille Nord Europe, F-59655 Villeneuve Dascq, France [ 212 ] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 464, Japan [ 213 ] Harvard Univ, Sch Med, Dept Genet, Boston, MA USA [ 214 ] Harvard Univ, Sch Med, Dept Mol Biol, Boston, MA USA [ 215 ] Massachusetts Gen Hosp, Diabet Unit, Boston, MA 02114 USA [ 216 ] Wake Forest Sch Med, Dept Biochem, Winston Salem, NC USA [ 217 ] Wake Forest Sch Med, Dept Internal Med, Winston Salem, NC USA [ 218 ] Hallym Univ, Dept Biomed Sci, Chunchon, Gangwon Do, South Korea [ 219 ] Univ Texas Hlth Sci Ctr Houston, Ctr Human Genet, Houston, TX 77030 USA [ 220 ] Imperial Coll Healthcare NHS Trust, London, England [ 221 ] Univ Calif San Francisco, Inst Human Genet, San Francisco, CA 94143 USA [ 222 ] Blood Syst Res Inst, San Francisco, CA USA [ 223 ] Natl Univ Singapore, Grad Sch Integrat Sci & Engn, Singapore 117548, Singapore [ 224 ] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore [ 225 ] Natl Univ Singapore, Dept Med, Singapore 117548, Singapore [ 226 ] Duke Natl Univ Singapore, Grad Sch Med, Singapore, Singapore [ 227 ] Univ Liverpool, Dept Biostat, Liverpool L69 3BX, Merseyside, England, Obstetrics & Gynecology, Radiology & Nuclear Medicine, Surgery, Epidemiology, Dermatology, Internal Medicine, Medical Microbiology & Infectious Diseases, Medical Research Council (MRC), National Institute for Health Research, ACS - Amsterdam Cardiovascular Sciences, Vascular Medicine, and Cardiology

Subjects
CHROMATIN, endocrine system diseases, South Asian Type 2 Diabetes (SAT2D) Consortium, SCALE ASSOCIATION ANALYSIS, Medizin, LOCI, Genome-wide association study, VARIANTS, 0302 clinical medicine, Risk Factors, IMPUTATION, Glucose homeostasis, 11 Medical and Health Sciences, Genetics & Heredity, Genetics, 0303 health sciences, IDENTIFY, Hispanic or Latino, 3. Good health, MAP, POPULATIONS, Medical genetics, Type 2 Diabetes Genetic Exploration by Nex-generation sequencing in muylti-Ethnic Samples (T2D-GENES) Consortium, Hispanic Americans, Life Sciences & Biomedicine, Asian Continental Ancestry Group, medicine.medical_specialty, European Continental Ancestry Group, TRANSETHNIC METAANALYSIS, 030209 endocrinology & metabolism, Single-nucleotide polymorphism, Biology, Polymorphism, Single Nucleotide, Article, White People, Sykursýki, 03 medical and health sciences, Asian People, SDG 3 - Good Health and Well-being, medicine, Humans, Genetic Predisposition to Disease, Allele, Asian Genetic Epidemiology Network Type 2 Diabetes (AGEN-T2D) Consortium, Alleles, 030304 developmental biology, Genetic association, Science & Technology, DIAbetes Genetics Replication And Meta-analysis (DIAGRAM) Consortium, Mexican American Type 2 Diabetes (MAT2D) Consortium, 06 Biological Sciences, Arfgengi, Genetic architecture, INDIVIDUALS, Diabetes Mellitus, Type 2, Case-Control Studies, GLUCOSE-HOMEOSTASIS, ASSOCIATION ANALYSES, Imputation (genetics), Developmental Biology, Genome-Wide Association Study
Abstract

To access publisher's full text version of this article click on the hyperlink at the bottom of the page To further understanding of the genetic basis of type 2 diabetes (T2D) susceptibility, we aggregated published meta-analyses of genome-wide association studies (GWAS), including 26,488 cases and 83,964 controls of European, east Asian, south Asian and Mexican and Mexican American ancestry. We observed a significant excess in the directional consistency of T2D risk alleles across ancestry groups, even at SNPs demonstrating only weak evidence of association. By following up the strongest signals of association from the trans-ethnic meta-analysis in an additional 21,491 cases and 55,647 controls of European ancestry, we identified seven new T2D susceptibility loci. Furthermore, we observed considerable improvements in the fine-mapping resolution of common variant association signals at several T2D susceptibility loci. These observations highlight the benefits of trans-ethnic GWAS for the discovery and characterization of complex trait loci and emphasize an exciting opportunity to extend insight into the genetic architecture and pathogenesis of human diseases across populations of diverse ancestry. Canadian Institutes of Health Research Medical Research Council UK G0601261 Mexico Convocatoria SSA/IMMS/ISSSTE-CONACYT 2012-2 clave 150352 IMSS R-2011-785-018 CONACYT Salud-2007-C01-71068 US National Institutes of Health DK062370 HG000376 DK085584 DK085545 DK073541 DK085501 Wellcome Trust WT098017 WT090532 WT090367 WT098381 WT081682 WT085475 info:eu-repo/grantAgreement/EC/FP7/201413

Published
2014

3. Replication of Caucasian loci associated with bone mineral density in Koreans

Author

Bok Ghee Han, Jeoung-Gil Lee, Hyung Jin Choi, Chan Soo Shin, Ye An Kim, and Nam H. Cho

Subjects
Genetic Markers, Male, musculoskeletal diseases, Genotyping Techniques, Bone density, Endocrinology, Diabetes and Metabolism, Population, Osteoporosis, Single-nucleotide polymorphism, Genome-wide association study, Polymorphism, Single Nucleotide, White People, Cohort Studies, Asian People, Bone Density, Polymorphism (computer science), medicine, Humans, Genetic Predisposition to Disease, education, Aged, Genetic association, Bone mineral, Genetics, Sex Characteristics, education.field_of_study, Lumbar Vertebrae, Femur Neck, business.industry, musculoskeletal, neural, and ocular physiology, Middle Aged, musculoskeletal system, medicine.disease, Genetic Loci, Female, Hip Joint, business, Genome-Wide Association Study
Abstract

Most bone mineral density (BMD) loci were reported in Caucasian genome-wide association studies (GWAS). This study investigated the association between 59 known BMD loci (+200 suggestive SNPs) and DXA-derived BMD in East Asian population with respect to sex and site specificity. We also identified four novel BMD candidate loci from the suggestive SNPs.Most GWAS have reported BMD-related variations in Caucasian populations. This study investigates whether the BMD loci discovered in Caucasian GWAS are also associated with BMD in East Asian ethnic samples.A total of 2,729 unrelated Korean individuals from a population-based cohort were analyzed. We selected 747 single-nucleotide polymorphisms (SNPs). These markers included 547 SNPs from 59 loci with genome-wide significance (GWS, p value less than 5 × 10(-8)) levels and 200 suggestive SNPs that showed weaker BMD association with p value less than 5 × 10(-5). After quality control, 535 GWS SNPs and 182 suggestive SNPs were included in the replication analysis.Of the 535 GWS SNPs, 276 from 25 loci were replicated (p 0.05) in the Korean population with 51.6 % replication rate. Of the 182 suggestive variants, 16 were replicated (p 0.05, 8.8 % of replication rate), and five reached a significant combined p value (less than 7.0 × 10(-5), 0.05/717 SNPs, corrected for multiple testing). Two markers (rs11711157, rs3732477) are for the same signal near the gene CPN2 (carboxypeptidase N, polypeptide 2). The other variants, rs6436440 and rs2291296, were located in the genes AP1S3 (adaptor-related protein complex 1, sigma 3 subunit) and RARB (retinoic acid receptor, beta).Our results illustrate ethnic differences in BMD susceptibility genes and underscore the need for further genetic studies in each ethnic group. We were also able to replicate some SNPs with suggestive associations. These SNPs may be BMD-related genetic markers and should be further investigated.

Published
2013

4. New susceptibility loci in MYL2, C12orf51 and OAS1 associated with 1-h plasma glucose as predisposing risk factors for type 2 diabetes in the Korean population

Author

Bok-Ghee Han, Myeong Chan Cho, Young-Jin Kim, Yoon Shin Cho, Joo-Yeon Hwang, Ju Young Lee, Jong-Young Lee, Bong-Jo Kim, Soo Heon Kwak, Yeonjung Kim, Ji Hee Oh, Min Jin Go, and Kyung Soo Park

Subjects
Adult, Blood Glucose, Male, medicine.medical_specialty, Myosin Light Chains, Genotype, Ubiquitin-Protein Ligases, Genome-wide association study, Type 2 diabetes, Biology, Polymorphism, Single Nucleotide, Asian People, Pregnancy, Risk Factors, Internal medicine, Republic of Korea, Genetic variation, 2',5'-Oligoadenylate Synthetase, Genetics, medicine, Genetic predisposition, Humans, Genetic Predisposition to Disease, Risk factor, Genetics (clinical), Aged, Genetic association, Glycemic, Fasting, Glucose Tolerance Test, Middle Aged, medicine.disease, Gestational diabetes, Diabetes, Gestational, Endocrinology, Diabetes Mellitus, Type 2, Genetic Loci, Hyperglycemia, Linear Models, Female, Cardiac Myosins, Genome-Wide Association Study
Abstract

Most recently, 1-h hyperglycemia has been recognized as an additional risk factor for type 2 diabetes. To date, previous genome-wide association studies for glycemic traits have a limited impact on the fasting state and 2-h plasma glucose level in an oral glucose challenge. To identify genetic susceptibility in different stages of glucose tolerance, we performed a meta-analysis for glycemic traits including 1-h plasma glucose (1-hPG) from 14 232 non-diabetic individuals in the Korean population. Newly implicated variants (MYL2, C12orf51 and OAS1) were found to be significantly associated with 1-hPG. We also demonstrated associations with gestational diabetes mellitus. Our results could provide additional insight into the genetic variation in the clinical range of glycemia.

Published
2013

5. A genome-wide association study of a coronary artery disease risk variant

Author

Ji-Young Lee, Bok-Soo Lee, Dong-Jik Shin, Kyung Woo Park, Young-Ah Shin, Kwang Joong Kim, Lyong Heo, Ji Young Lee, Yun Kyoung Kim, Young Jin Kim, Chang Bum Hong, Sang-Hak Lee, Dankyu Yoon, Hyo Jung Ku, Il-Young Oh, Bong-Jo Kim, Juyoung Lee, Seon-Joo Park, Jimin Kim, Hye-kyung Kawk, Jong-Eun Lee, Hye-kyung Park, Jae-Eun Lee, Hye-young Nam, Hyun-young Park, Chol Shin, Mitsuhiro Yokota, Hiroyuki Asano, Masahiro Nakatochi, Tatsuaki Matsubara, Hidetoshi Kitajima, Ken Yamamoto, Hyung-Lae Kim, Bok-Ghee Han, Myeong-Chan Cho, Yangsoo Jang, Hyo-Soo Kim, Jeong Euy Park, and Jong-Young Lee

Subjects
Adult, Male, Genotyping Techniques, Single-nucleotide polymorphism, Genome-wide association study, Coronary Artery Disease, Biology, Polymorphism, Single Nucleotide, Asian People, Risk Factors, Genetics, Genetic predisposition, Humans, SNP, Genetic Predisposition to Disease, Genetics (clinical), Aged, Genetic association, Genome, Human, Middle Aged, Tag SNP, Genetic Loci, Case-Control Studies, Female, Imputation (genetics), Genome-Wide Association Study, SNP array
Abstract

Although over 30 common genetic susceptibility loci have been identified to be independently associated with coronary artery disease (CAD) risk through genome-wide association studies (GWAS), genetic risk variants reported to date explain only a small fraction of heritability. To identify novel susceptibility variants for CAD and confirm those previously identified in European population, GWAS and a replication study were performed in the Koreans and Japanese. In the discovery stage, we genotyped 2123 cases and 3591 controls with 521 786 SNPs using the Affymetrix SNP Array 6.0 chips in Korean. In the replication, direct genotyping was performed using 3052 cases and 4976 controls from the KItaNagoya Genome study of Japan with 14 selected SNPs. To maximize the coverage of the genome, imputation was performed based on 1000 Genome JPT+CHB and 5.1 million SNPs were retained. CAD association was replicated for three GWAS-identified loci (1p13.3/SORT1 (rs599839), 9p21.3/CDKN2A/2B (rs4977574), and 11q22.3/ PDGFD (rs974819)) in Koreans. From GWAS and a replication, SNP rs3782889 showed a strong association (combined P=3.95 × 10(-14)), although the association of SNP rs3782889 doesn't remain statistically significant after adjusting for SNP rs11066015 (proxy SNP with BRAP (r(2)=1)). But new possible CAD-associated variant was observed for rs9508025 (FLT1), even though its statistical significance did marginally reach at the genome-wide a significance level (combined P=6.07 × 10(-7)). This study shows that three CAD susceptibility loci, which were previously identified in European can be directly replicated in Koreans and also provides additional evidences implicating suggestive loci as risk variants for CAD in East Asian.

Published
2013

6. Identification of putative biomarkers for type 2 diabetes using metabolomics in the Korea Association REsource (KARE) cohort

Author

Tao Xu, Yeon Jung Kim, Young Ho Lee, Karsten Suhre, Bong Jo Kim, Jerzy Adamski, Jeongmin Kim, Annette Peters, Moonsuk Nam, Wolfgang Rathmann, Rui Wang-Sattler, Nam Hee Kim, Bok Ghee Han, Kwang Youl Kim, Sang Yun Cho, and Heun Sik Lee

Subjects
0301 basic medicine, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Metabolite, Clinical Biochemistry, 030209 endocrinology & metabolism, Genome-wide association study, Type 2 diabetes, Biology, Biochemistry, 03 medical and health sciences, chemistry.chemical_compound, symbols.namesake, 0302 clinical medicine, Metabolomics, medicine, Genetics, nutritional and metabolic diseases, medicine.disease, 030104 developmental biology, Bonferroni correction, chemistry, Multiple comparisons problem, Cohort, symbols, Cohort study
Abstract

Type 2 diabetes (T2D) is a multifactorial disease resulting from a complex interaction between environmental and genetic risk factors. Metabolomics provide a logical framework that reflects the functional endpoints of biological processes being triggered by genetic information and various external influences. Identification of metabolite biomarkers can shed insight into etiological pathways and improve the prediction of disease risk. Here, we aimed to identify serum metabolites as putative biomarkers for T2D and their association with genetic variants in the Korean population. A targeted metabolomics approach was employed to quantify serum metabolites for 2240 participants in the Korea Association REsource (KARE) cohort. T2D-related metabolites were identified by statistical methods including multivariable linear and logistic regression, and were independently replicated in the Cooperative Health Research in the Region of Augsburg (KORA) cohort. Additionally, by combining a genome wide association study (GWAS) with metabolomics, genetic variants associated with the identified T2D-related metabolites were uncovered. 123 metabolites were quantified from fasting serum samples and four metabolites, hexadecanoylcarnitine (C16), glycine, lysophosphatidylcholine acyl C18:2 (lysoPC a C18:2), and phosphatidylcholine acyl-alkyl C36:0 (PC ae C36:0), were significantly altered in T2D compared to non-T2D subjects (after the Bonferroni correction for multiple testing with P

Published
2016

7. Meta-analysis of genome-wide association studies identifies eight new loci for type 2 diabetes in east Asians

Author

Bok Ghee Han, Congrong Wang, Wing-Yee So, Ying Wu, Rong Zhang, Xueling Sim, Norihiro Kato, Eitaro Nakashima, Qiuyin Cai, Tien-Jyun Chang, Jiro Nakamura, Wei Lu, Mark Seielstad, Yu-Tang Gao, Juliana C.N. Chan, Fumihiko Takeuchi, Jer-Yuarn Wu, Lee-Ming Chuang, Young Min Cho, Hyung Lae Kim, Yik Ying Teo, Andrew P. Morris, Nam H. Cho, Daniel P.K. Ng, Rick Twee-Hee Ong, Cheng Hu, Kyong Soo Park, Sangsoo Kim, Shiro Maeda, Toshimasa Yamauchi, Fuu Jen Tsai, Yoon Shin Cho, Hiroshi Ikegami, Ronald C.W. Ma, Jirong Long, Ken Yamamoto, Yi-Cheng Chang, Xiao-Ou Shu, Karen L. Mohlke, Wei Zheng, Mitsuhiro Yokota, Soo Heon Kwak, Yuan-Tsong Chen, Chien Hsiun Chen, Linda S. Adair, Yun Li, Nanette R. Lee, Young-Jin Kim, Jeannette Lee, Li Ching Chang, Keizo Ohnaka, Ryoichi Takayanagi, Min Jin Go, Wan Ting Tay, Jianjun Liu, Tin Aung, Jong-Young Lee, Hara Kazuo, Yuqian Bao, Weiping Jia, Tien Yin Wong, E. Shyong Tai, Takashi Kadowaki, Mark I. McCarthy, Åsa K. Hedman, and Frank B. Hu

Subjects
Genetics, endocrine system, education.field_of_study, endocrine system diseases, PEPD, Population, Case-control study, Genome-wide association study, Type 2 diabetes, Biology, medicine.disease, Polymorphism (computer science), Diabetes mellitus, medicine, education, Genetic association
Abstract

We conducted a three-stage genetic study to identify susceptibility loci for type 2 diabetes (T2D) in east Asian populations. We followed our stage 1 meta-analysis of eight T2D genome-wide association studies (6,952 cases with T2D and 11,865 controls) with a stage 2 in silico replication analysis (5,843 cases and 4,574 controls) and a stage 3 de novo replication analysis (12,284 cases and 13,172 controls). The combined analysis identified eight new T2D loci reaching genome-wide significance, which mapped in or near GLIS3, PEPD, FITM2-R3HDML-HNF4A, KCNK16, MAEA, GCC1-PAX4, PSMD6 and ZFAND3. GLIS3, which is involved in pancreatic beta cell development and insulin gene expression, is known for its association with fasting glucose levels. The evidence of an association with T2D for PEPD and HNF4A has been shown in previous studies. KCNK16 may regulate glucose-dependent insulin secretion in the pancreas. These findings, derived from an east Asian population, provide new perspectives on the etiology of T2D.

Published
2011

8. Exome sequencing and subsequent association studies identify five amino acid-altering variants influencing human height

Author

Kyu-Heum Baik, Jung-Ah Hwang, Hiroshi Inoue, Hye-Yeon Choi, Hwanseok Rhee, Young-Mi Park, Ji Eun Lee, Karen E. Heath, Gap-Seok Yang, Jae-Jung Kim, Bok-Ghee Han, Kiejung Park, InSong Koh, Jong-Keuk Lee, Yeon-Su Lee, Tae Soo Kwon, and Han-Wook Yoo

Subjects
Male, Genetics, Nonsynonymous substitution, Korea, Genome, Human, Gene Expression Profiling, Sequence Analysis, DNA, Biology, medicine.disease, Polymorphism, Single Nucleotide, Body Height, Human genetics, Idiopathic short stature, medicine, Trait, Humans, Noonan syndrome, Exome, Female, Human height, Growth Disorders, Genetics (clinical), Exome sequencing, Genetic association
Abstract

Height is a highly heritable trait that involves multiple genetic loci. To identify causal variants that influence stature, we sequenced whole exomes of four children with idiopathic short stature. Ninety-five nonsynonymous single-nucleotide polymorphisms (nsSNPs) were selected as potential candidate variants. We performed association analysis in 740 cohort individuals and identified 11 nsSNPs in 10 loci (DIS3L2, ZBTB38, FAM154A, PTCH1, TSSC4, KIF18A, GPR133, ACAN, FAM59A, and NINL) associated with adult height (P < 0.05), including five novel loci. Of these, two nsSNPs (TSSC4 and KIF18A loci) were significant at P < 0.05 in the replication study (n = 1,000) and five (ZBTB38, FAM154A, TSSC4, KIF18A, and FAM59A loci) were significant at P < 0.01 in the combined analysis (n = 1,740). Together, the five nsSNPs accounted for approximately 2.5% of the height variation. This study demonstrated the utility of next-generation sequencing in identifying genetic variants and loci associated with complex traits.

Published
2011

9. Meta-analysis of genome-wide association studies identifies common variants associated with blood pressure variation in east Asians

Author

Masato Isono, Toshio Ogihara, Rick Twee-Hee Ong, Toru Nabika, Jiang He, Shotai Kobayashi, Min Jin Go, Sung Soo Kim, Xueling Sim, Norihiro Kato, Fumihiko Takeuchi, Mitsuhiro Yokota, Jong-Young Lee, Yasuharu Tabara, Xuegong Zhang, Dingliang Zhu, Mark Seielstad, Naoharu Iwai, Tien Yin Wong, Tin Aung, Wei Huang, Dongfeng Gu, Yun Ju Sung, Bok Ghee Han, Tomohiro Katsuya, Ryoichi Takayanagi, Xueya Zhou, Yuan-Tsong Chen, Tanika N. Kelly, Yoshihiro Kokubo, Li Ching Chang, Wan Ting Tay, Jer-Yuarn Wu, Yoon Shin Cho, Keizo Ohnaka, Cashell E. Jaquish, Young-Jin Kim, Jianjun Liu, Tetsuro Miki, Ken Yamamoto, E. Shyong Tai, Chien Hsiun Chen, Yik Ying Teo, Eitaro Nakashima, James E. Hixson, Takao Sugiyama, Yi Zhang, Yukio Yamori, and Jae Pil Jeon

Subjects
Genetics, Asia, Eastern, Systole, Hemodynamics, Blood Pressure, Genome-wide association study, Biology, Polymorphism, Single Nucleotide, Article, White People, Blood pressure, Asian People, Gene Frequency, Diastole, Polymorphism (computer science), Meta-analysis, Humans, cardiovascular diseases, Allele frequency, Genotyping, circulatory and respiratory physiology, Genome-Wide Association Study, Genetic association
Abstract

We conducted a meta-analysis of genome-wide association studies of systolic (SBP) and diastolic (DBP) blood pressure in 19,608 subjects of east Asian ancestry from the AGEN-BP consortium followed up with de novo genotyping (n = 10,518) and further replication (n = 20,247) in east Asian samples. We identified genome-wide significant (P < 5 × 10(-8)) associations with SBP or DBP, which included variants at four new loci (ST7L-CAPZA1, FIGN-GRB14, ENPEP and NPR3) and a newly discovered variant near TBX3. Among the five newly discovered variants, we obtained significant replication in the independent samples for all of these loci except NPR3. We also confirmed seven loci previously identified in populations of European descent. Moreover, at 12q24.13 near ALDH2, we observed strong association signals (P = 7.9 × 10(-31) and P = 1.3 × 10(-35) for SBP and DBP, respectively) with ethnic specificity. These findings provide new insights into blood pressure regulation and potential targets for intervention.

Published
2011

10. A genome-wide association analysis reveals 1p31 and 2p13.3 as susceptibility loci for Kawasaki disease

Author

Jae-Jung, Kim, Young Mi, Hong, Saejung, Sohn, Gi Young, Jang, Kee-Soo, Ha, Sin Weon, Yun, Myung Ki, Han, Kyung-Yil, Lee, Min Seob, Song, Hyoung Doo, Lee, Dong Soo, Kim, Jong-Eun, Lee, Eun-Soon, Shin, Ji-Hyun, Jang, Yeon-Su, Lee, Sook-Young, Kim, Jong-Young, Lee, Bok-Ghee, Han, Jer-Yuarn, Wu, Kwi-Joo, Kim, Young-Mi, Park, Eul-Joo, Seo, In-Sook, Park, Jong-Keuk, Lee, and Jae-Moo, Lee

Subjects
Adult, Male, Linkage disequilibrium, Mucocutaneous zone, Locus (genetics), Genome-wide association study, Mucocutaneous Lymph Node Syndrome, Biology, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Asian People, Gene mapping, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetics (clinical), Coronary Aneurysm, Odds ratio, medicine.disease, Chromosomes, Human, Pair 1, Genetic Loci, Chromosomes, Human, Pair 2, Immunology, Female, Kawasaki disease, Genome-Wide Association Study, SNP array
Abstract

Kawasaki disease (KD) is an acute self-limited vasculitis of infants and children that manifests as fever and signs of mucocutaneous inflammation. Coronary artery aneurysms develop in approximately 15-25% of untreated children. Although the etiology of KD is largely unknown, epidemiologic data suggest the importance of genetic factors in the susceptibility to KD. In order to identify genetic variants that influence KD susceptibility, we performed a genome-wide association study (GWAS) using Affymetrix SNP array 6.0 in 186 Korean KD patients and 600 healthy controls; 18 and 26 genomic regions with one or more sequence variants were associated with KD and KD with coronary artery lesions (CALs), respectively (p

Published
2011

11. Development of SNP-based human identification system

Author

Jong-Keuk Lee, Jae-Jung Kim, Hae-In Lee, Bok-Ghee Han, and Han-Wook Yoo

Subjects
Genetic Markers, Male, Genetics, Amelogenin, Genotype, Racial Groups, Kruppel-Like Transcription Factors, Single-nucleotide polymorphism, Sex Determination Processes, Biology, Tag SNP, Molecular Inversion Probe, DNA Fingerprinting, Polymerase Chain Reaction, Polymorphism, Single Nucleotide, Pathology and Forensic Medicine, SNP genotyping, Republic of Korea, Humans, SNP, Female, Human genome, Sequence Analysis, Genotyping, SNP array
Abstract

Single nucleotide polymorphisms (SNPs) appeal to the forensic DNA community because of their abundance in the human genome, low mutation rate, small amplicon size, and feasibility of high-throughput genotyping technologies.In an initial screening, we identified six SNP markers of sex determination by resequencing the amelogenin genes and the zinc finger protein genes located on the sex chromosomes. Furthermore, for use in human identification,we selected 30 highly polymorphic autosomal SNP markers from among a human population and examined the potential utility of these SNP markers for human identification.The combined mean match probability of 30 SNP markers was 4.83 x 10(-13). Using genotyping data from 8,842 unrelated Korean individuals, we also found that discrimination power increased 10-fold for the addition of every five SNP markers in human identification. In this study, we demonstrated that SNP markers are very useful for sex determination and human identification, even in a very homogeneous population.

Published
2009

12. Association of a RUNX2 Promoter Polymorphism with Bone Mineral Density in Postmenopausal Korean Women

Author

Ghi Su Kim, Eui Kyun Park, Hee Jung Lee, Bok Ghee Han, Joo Yeon Hwang, Jong-Young Lee, Jung Min Koh, Seung Hun Lee, Kang Yell Choi, Tae-Ho Kim, and Shin Yoon Kim

Subjects
Adult, musculoskeletal diseases, medicine.medical_specialty, Genotype, Endocrinology, Diabetes and Metabolism, Osteoporosis, Population, Core Binding Factor Alpha 1 Subunit, Single-nucleotide polymorphism, Polymorphism, Single Nucleotide, Bone remodeling, Endocrinology, Gene Frequency, Bone Density, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Orthopedics and Sports Medicine, Femur, Promoter Regions, Genetic, education, Alleles, Aged, Aged, 80 and over, Bone mineral, education.field_of_study, Korea, Polymorphism, Genetic, business.industry, musculoskeletal, neural, and ocular physiology, Heterozygote advantage, Exons, Middle Aged, musculoskeletal system, medicine.disease, Postmenopause, Female, business
Abstract

Osteoporosis is characterized by impaired osteoblastogenesis. Bone mineral density (BMD) is a major determinant of bone strength. RUNX2 is an osteoblast-specific transcription factor involved in osteoblast differentiation and ossification. To determine whether RUNX2 is associated with BMD in an ethnically distinct population, we investigated SNPs within the two RUNX2 promoters (P1 and P2) using the Illuminar GoldenGate system in 729 postmenopausal Korean women. Subjects bearing the minor homozygote genotype (CC) at the RUNX2 −1025 T > C SNP (rs7771980) located in P2 showed a significant association with reduced lumbar spine BMD (p = 0.02) and BMDs at proximal femur sites (trochanter, p = 0.05; total femur, p = 0.04) compared with subjects carrying the major homozygote genotype (TT) or the heterozygote genotype (TC), respectively. These results present an interesting genotype association complementary to the previously reported association of BMD with the RUNX2 −1025 T > C P2 SNP in Spanish and Australian cohorts. Therefore, we suggest that the RUNX2 P2 polymorphism (−1025 T > C) may be a useful genetic marker for bone metabolism and may play an important role in BMD in postmenopausal Korean women.

Published
2009

13. Recapitulation of previous genome-wide association studies with two distinct pathophysiological entities of gastric cancer in the Korean population

Author

Bok-Ghee Han, Il Ju Choi, Jong-Young Lee, Min Jin Go, Duk-Hwan Kim, Young-Woo Kim, Ju Young Lee, Bong-Jo Kim, Yeon-Su Lee, Sung Kim, Yongick Ji, Joobae Park, Jae Hyung Noh, Young-Jin Kim, Sook-Young Kim, Keun Won Ryu, Joo-Yeon Hwang, Tae Sung Sohn, and Lyong Heo

Subjects
Male, medicine.medical_specialty, Genome-wide association study, Biology, Malignancy, Gastroenterology, Asian People, Stomach Neoplasms, Internal medicine, Republic of Korea, Genetics, medicine, Humans, Genetic Predisposition to Disease, Genetics (clinical), Genetic association, Genome, Human, Korean population, Cancer, Odds ratio, Middle Aged, medicine.disease, Confidence interval, Pathophysiology, Case-Control Studies, Female, Genome-Wide Association Study
Abstract

Gastric cancer (GC) is the most common malignancy. The incidence rates remain remarkably high in East Asians. Although genome-wide association studies in the Han Chinese and Japanese populations have so far yielded susceptibility loci for GC, these findings need to be validated in an independent ethnic group. To identify the potential heterogeneity by histological classified subtypes (intestinal and diffuse), we examined the previously reported associations in the Korean population. PRKAA1 at 5p13.1 was found to be more strongly associated with intestinal type (odds ratio, OR=1.39, 95% CI (confidence interval) =1.22-1.58, P=3.77 × 10(-7)) than diffuse type. In addition, PSCA at 8q23.3 was significantly replicated in diffuse type (OR=1.49, 95% CI=1.32-1.67, P=2.43 × 10(-11)) but far less significant in intestinal type. In conclusion, these findings could bring additional insights into the etiologic heterogeneity in gastric carcinogenesis mechanisms.

Published
2013

14. Expression of P2 receptors in human B cells and Epstein-Barr virus-transformed lymphoblastoid cell lines

Author

Bok Ghee Han, In Deok Kong, Kyu Sang Park, Dong Hyeon Lee, and Jun Woo Kim

Subjects
lcsh:Immunologic diseases. Allergy, Herpesvirus 4, Human, Immunology, Cell Separation, P2 receptor, Biology, medicine.disease_cause, Adenosine Triphosphate, Gene expression, Extracellular, medicine, Humans, RNA, Messenger, Receptor, Cell Line, Transformed, Regulation of gene expression, B-Lymphocytes, Receptors, Purinergic P2, Purinergic receptor, Molecular biology, Epstein–Barr virus, In vitro, Gene Expression Regulation, Calcium, lcsh:RC581-607, Research Article
Abstract

BackgroundEpstein-Barr virus (EBV) infection immortalizes primary B cells in vitro and generates lymphoblastoid cell lines (LCLs), which are used for several purposes in immunological and genetic studies. Purinergic receptors, consisting of P2X and P2Y, are activated by extracellular nucleotides in most tissues and exert various physiological effects. In B cells, especially EBV-induced LCLs, their expression and function have not been well studied. We investigated the expression of P2 receptors on primary human B cells and LCLs using the quantitative reverse transcriptase-polymerase chain reaction (RT-PCR) method for revealing the gene expression profile of the P2 receptor subtypes and their changes during transformation.ResultsThe mRNA transcripts of most P2 receptors were detected in primary B cells; the expression of P2X3and P2X7receptors was the lowest of all the P2 receptors. By contrast, LCLs expressed several dominant P2 receptors – P2X4, P2X5, and P2Y11– in amounts similar to those seen in B cells infected with EBV for 2 weeks. The amount of most P2 subtypes in LCLs or EBV-infected B cells was lower than in normal B cells. However, the amount of P2X7receptor expressed in LCLs was higher. Protein expression was studied using Western blotting to confirm the mRNA findings for P2X1, P2X4, P2X7, P2Y1, and P2Y11receptors. ATP increased the intracellular free Ca2+concentration ([Ca2+]i) by enhancing the Ca2+influx in both B cells and LCLs in a dose-dependent manner.ConclusionThese findings describe P2 receptor expression profiles and the effects of purinergic stimuli on B cells and suggest some plasticity in the expression of the P2 receptor phenotype. This may help explain the nature and effect of P2 receptors on B cells and their role in altering the characteristics of LCLs.

Published
2006

15. Aging alters the apoptotic response to genotoxic stress

Author

Jan Vijg, Woo Ho Kim, Yousin Suh, Sang Chul Park, Bok Ghee Han, and Kang Ae Lee

Subjects
Aging, Alkylation, DNA damage, Liver cytology, Apoptosis, General Medicine, Genotoxic Stress, Biology, Methyl Methanesulfonate, Rats, Inbred F344, General Biochemistry, Genetics and Molecular Biology, Rats, Liver, Immunology, Cancer research, Animals, Female, Injections, Intraperitoneal, DNA Damage, Mutagens
Published
2002

16. Copy number variation at leptin receptor gene locus associated with metabolic traits and the risk of type 2 diabetes mellitus

Author

Sung Mi Shim, Jae Pil Jeon, Bok Ghee Han, Hye Young Nam, Gil Mi Ryu, Eun Jung Hong, and Hyung Lae Kim

Subjects
Blood Glucose, Male, lcsh:QH426-470, lcsh:Biotechnology, Gene Dosage, Locus (genetics), Biology, Gene dosage, Exon, lcsh:TP248.13-248.65, Genetic variation, Genetics, Humans, Genetic Predisposition to Disease, Copy-number variation, Gene, Korea, Leptin receptor, lcsh:Genetics, Cholesterol, Diabetes Mellitus, Type 2, Genetic Loci, Receptors, Leptin, Female, DNA microarray, Research Article, Biotechnology
Abstract

Background Recent efforts have been made to link complex human traits and disease susceptibility to DNA copy numbers. The leptin receptor (LEPR) has been implicated in obesity and diabetes. Mutations and genetic variations of LEPR gene have been discovered in rodents and humans. However, the association of DNA copy number variations at the LEPR gene locus with human complex diseases has not been reported. In an attempt to study DNA copy number variations associated with metabolic traits and type 2 diabetes mellitus (T2DM), we targeted the LEPR gene locus in DNA copy number analyses. Results We identified DNA copy number variations at the LEPR gene locus among a Korean population using genome-wide SNP chip data, and then quantified copy numbers of the E2 DNA sequence in the first two exons overlapped between LEPR and LEPROT genes by the quantitative multiplex PCR of short fluorescent fragment (QMPSF) method. Among the non-diabetic subjects (n = 1,067), lower E2 DNA copy numbers were associated with higher fasting glucose levels in men (p = 1.24 × 10-7) and women (p = 9.45 × 10-5), as well as higher total cholesterol levels in men (p = 9.96 × 10-7). In addition, the significant association between lower E2 DNA copy numbers and lower level of postprandial 2hr insulin was evident only in non-diabetic women, whereas some obesity-related phenotypes and total cholesterol level exhibited significant associations only in non-diabetic men. Logistic regression analysis indicated that lower E2 DNA copy numbers were associated with T2DM (odds ratio, 1.92; 95% CI, 1.26~2.96; p < 0.003) in our nested case-control study. Interestingly, the E2 DNA copy number exhibited a negative correlation with LEPR gene expression, but a positive correlation with LEPROT gene expression. Conclusions This work suggests that a structural variation at the LEPR gene locus is functionally associated with complex metabolic traits and the risk of T2DM.

Published
2010

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