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Your search keyword '"Chang, Kyong-Mi"' showing total 5 results
Start Over Author "Chang, Kyong-Mi" Journal nature genetics
5 results on '"Chang, Kyong-Mi"'

1. Integrative common and rare variant analyses provide insights into the genetic architecture of liver cirrhosis.

Author

Ghouse, Jonas, Sveinbjörnsson, Gardar, Vujkovic, Marijana, Seidelin, Anne-Sofie, Gellert-Kristensen, Helene, Ahlberg, Gustav, Tragante, Vinicius, Rand, Søren, Brancale, Joseph, Vilarinho, Silvia, Lundegaard, Pia, Sørensen, Erik, Erikstrup, Christian, Bruun, Mie, Jensen, Bitten, Brunak, Søren, Banasik, Karina, Ullum, Henrik, Verweij, Niek, Lotta, Luca, Baras, Aris, Mirshahi, Tooraj, Carey, David, Kaplan, David, Lynch, Julie, Morgan, Timothy, Schwantes-An, Tae-Hwi, Dochtermann, Daniel, Pyarajan, Saiju, Tsao, Philip, Laisk, Triin, Mägi, Reedik, Kozlitina, Julia, Tybjærg-Hansen, Anne, Jones, David, Knowlton, Kirk, Nadauld, Lincoln, Ferkingstad, Egil, Björnsson, Einar, Ulfarsson, Magnus, Sturluson, Árni, Sulem, Patrick, Pedersen, Ole, Ostrowski, Sisse, Gudbjartsson, Daniel, Stefansson, Kari, Olesen, Morten, Chang, Kyong-Mi, Holm, Hilma, Bundgaard, Henning, and Stender, Stefan

Subjects
Humans, Liver Cirrhosis, Genome-Wide Association Study, Genetic Predisposition to Disease, Liver Neoplasms, Carcinoma, Hepatocellular, Alanine Transaminase, Polymorphism, Single Nucleotide, Male, Lipase, Female, gamma-Glutamyltransferase, Membrane Proteins, Cohort Studies, Case-Control Studies, Multifactorial Inheritance, Risk Factors, Genetic Variation
Abstract

We report a multi-ancestry genome-wide association study on liver cirrhosis and its associated endophenotypes, alanine aminotransferase (ALT) and γ-glutamyl transferase. Using data from 12 cohorts, including 18,265 cases with cirrhosis, 1,782,047 controls, up to 1 million individuals with liver function tests and a validation cohort of 21,689 cases and 617,729 controls, we identify and validate 14 risk associations for cirrhosis. Many variants are located near genes involved in hepatic lipid metabolism. One of these, PNPLA3 p.Ile148Met, interacts with alcohol intake, obesity and diabetes on the risk of cirrhosis and hepatocellular carcinoma (HCC). We develop a polygenic risk score that associates with the progression from cirrhosis to HCC. By focusing on prioritized genes from common variant analyses, we find that rare coding variants in GPAM associate with lower ALT, supporting GPAM as a potential target for therapeutic inhibition. In conclusion, this study provides insights into the genetic underpinnings of cirrhosis.

Published
2024

2. A multiancestry genome-wide association study of unexplained chronic ALT elevation as a proxy for nonalcoholic fatty liver disease with histological and radiological validation

Author

Vujkovic, Marijana, Ramdas, Shweta, Lorenz, Kim M, Guo, Xiuqing, Darlay, Rebecca, Cordell, Heather J, He, Jing, Gindin, Yevgeniy, Chung, Chuhan, Myers, Robert P, Schneider, Carolin V, Park, Joseph, Lee, Kyung Min, Serper, Marina, Carr, Rotonya M, Kaplan, David E, Haas, Mary E, MacLean, Matthew T, Witschey, Walter R, Zhu, Xiang, Tcheandjieu, Catherine, Kember, Rachel L, Kranzler, Henry R, Verma, Anurag, Giri, Ayush, Klarin, Derek M, Sun, Yan V, Huang, Jie, Huffman, Jennifer E, Creasy, Kate Townsend, Hand, Nicholas J, Liu, Ching-Ti, Long, Michelle T, Yao, Jie, Budoff, Matthew, Tan, Jingyi, Li, Xiaohui, Lin, Henry J, Chen, Yii-Der Ida, Taylor, Kent D, Chang, Ruey-Kang, Krauss, Ronald M, Vilarinho, Silvia, Brancale, Joseph, Nielsen, Jonas B, Locke, Adam E, Jones, Marcus B, Verweij, Niek, Baras, Aris, Reddy, K Rajender, Neuschwander-Tetri, Brent A, Schwimmer, Jeffrey B, Sanyal, Arun J, Chalasani, Naga, Ryan, Kathleen A, Mitchell, Braxton D, Gill, Dipender, Wells, Andrew D, Manduchi, Elisabetta, Saiman, Yedidya, Mahmud, Nadim, Miller, Donald R, Reaven, Peter D, Phillips, Lawrence S, Muralidhar, Sumitra, DuVall, Scott L, Lee, Jennifer S, Assimes, Themistocles L, Pyarajan, Saiju, Cho, Kelly, Edwards, Todd L, Damrauer, Scott M, Wilson, Peter W, Gaziano, J Michael, O’Donnell, Christopher J, Khera, Amit V, Grant, Struan FA, Brown, Christopher D, Tsao, Philip S, Saleheen, Danish, Lotta, Luca A, Bastarache, Lisa, Anstee, Quentin M, Daly, Ann K, Meigs, James B, Rotter, Jerome I, Lynch, Julie A, Rader, Daniel J, Voight, Benjamin F, and Chang, Kyong-Mi

Subjects
Genetics, Liver Disease, Human Genome, Digestive Diseases, Chronic Liver Disease and Cirrhosis, Aetiology, 2.1 Biological and endogenous factors, Alanine Transaminase, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Genome-Wide Association Study, Humans, Intracellular Signaling Peptides and Proteins, Lipase, Membrane Proteins, Non-alcoholic Fatty Liver Disease, Polymorphism, Single Nucleotide, Protein Serine-Threonine Kinases, Regeneron Genetics Center, Geisinger-Regeneron DiscovEHR Collaboration, EPoS Consortium, VA Million Veteran Program, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Nonalcoholic fatty liver disease (NAFLD) is a growing cause of chronic liver disease. Using a proxy NAFLD definition of chronic elevation of alanine aminotransferase (cALT) levels without other liver diseases, we performed a multiancestry genome-wide association study (GWAS) in the Million Veteran Program (MVP) including 90,408 cALT cases and 128,187 controls. Seventy-seven loci exceeded genome-wide significance, including 25 without prior NAFLD or alanine aminotransferase associations, with one additional locus identified in European American-only and two in African American-only analyses (P

Published
2022

3. Discovery of 318 new risk loci for type 2 diabetes and related vascular outcomes among 1.4 million participants in a multi-ancestry meta-analysis

Author

Vujkovic, Marijana, Keaton, Jacob M., Lynch, Julie A., Miller, Donald R., Zhou, Jin, Tcheandjieu, Catherine, Huffman, Jennifer E., Assimes, Themistocles L., Lorenz, Kimberly, Zhu, Xiang, Hilliard, Austin T., Judy, Renae L., Huang, Jie, Lee, Kyung M., Klarin, Derek, Pyarajan, Saiju, Danesh, John, Melander, Olle, Rasheed, Asif, Mallick, Nadeem H., Hameed, Shahid, Qureshi, Irshad H., Afzal, Muhammad Naeem, Malik, Uzma, Jalal, Anjum, Abbas, Shahid, Sheng, Xin, Gao, Long, Kaestner, Klaus H., Susztak, Katalin, Sun, Yan V., DuVall, Scott L., Cho, Kelly, Lee, Jennifer S., Gaziano, J. Michael, Phillips, Lawrence S., Meigs, James B., Reaven, Peter D., Wilson, Peter W., Edwards, Todd L., Rader, Daniel J., Damrauer, Scott M., O’Donnell, Christopher J., Tsao, Philip S., Chang, Kyong-Mi, Voight, Benjamin F., and Saleheen, Danish

Published
2020
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4. Genome-wide association analysis of venous thromboembolism identifies new risk loci and genetic overlap with arterial vascular disease

Author

Klarin, Derek, Busenkell, Emma, Judy, Renae, Lynch, Julie, Levin, Michael, Haessler, Jeffery, Aragam, Krishna, Chaffin, Mark, Haas, Mary, Lindström, Sara, Assimes, Themistocles L., Huang, Jie, Min Lee, Kyung, Shao, Qing, Huffman, Jennifer E., Kabrhel, Christopher, Huang, Yunfeng, Sun, Yan V., Vujkovic, Marijana, Saleheen, Danish, Miller, Donald R., Reaven, Peter, DuVall, Scott, Boden, William E., Pyarajan, Saiju, Reiner, Alex P., Trégouët, David-Alexandre, Henke, Peter, Kooperberg, Charles, Gaziano, J. Michael, Concato, John, Rader, Daniel J., Cho, Kelly, Chang, Kyong-Mi, Wilson, Peter W. F., Smith, Nicholas L., O’Donnell, Christopher J., Tsao, Philip S., Kathiresan, Sekar, Obi, Andrea, Damrauer, Scott M., and Natarajan, Pradeep

Abstract

Venous thromboembolism is a significant cause of mortality1, yet its genetic determinants are incompletely defined. We performed a discovery genome-wide association study in the Million Veteran Program and UK Biobank, with testing of approximately 13 million DNA sequence variants for association with venous thromboembolism (26,066 cases and 624,053 controls) and meta-analyzed both studies, followed by independent replication with up to 17,672 venous thromboembolism cases and 167,295 controls. We identified 22 previously unknown loci, bringing the total number of venous thromboembolism-associated loci to 33, and subsequently fine-mapped these associations. We developed a genome-wide polygenic risk score for venous thromboembolism that identifies 5% of the population at an equivalent incident venous thromboembolism risk to carriers of the established factor V Leiden p.R506Q and prothrombin G20210A mutations. Our data provide mechanistic insights into the genetic epidemiology of venous thromboembolism and suggest a greater overlap among venous and arterial cardiovascular disease than previously thought.

Published
2019
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5. Genetics of blood lipids among ~300,000 multi-ethnic participants of the Million Veteran Program

Author

Klarin, Derek, Damrauer, Scott M., Cho, Kelly, Sun, Yan V., Teslovich, Tanya M., Honerlaw, Jacqueline, Gagnon, David R., DuVall, Scott L., Li, Jin, Peloso, Gina M., Chaffin, Mark, Small, Aeron M., Huang, Jie, Tang, Hua, Lynch, Julie A., Ho, Yuk-Lam, Liu, Dajiang J., Emdin, Connor A., Li, Alexander H., Huffman, Jennifer E., Lee, Jennifer S., Natarajan, Pradeep, Chowdhury, Rajiv, Saleheen, Danish, Vujkovic, Marijana, Baras, Aris, Pyarajan, Saiju, Di Angelantonio, Emanuele, Neale, Benjamin M., Naheed, Aliya, Khera, Amit V., Danesh, John, Chang, Kyong-Mi, Abecasis, Gonçalo, Willer, Cristen, Dewey, Frederick E., Carey, David J., Concato, John, Gaziano, J. Michael, O’Donnell, Christopher J., Tsao, Philip S., Kathiresan, Sekar, Rader, Daniel J., Wilson, Peter W. F., and Assimes, Themistocles L.

Abstract

The Million Veteran Program (MVP) was established in 2011 as a national research initiative to determine how genetic variation influences the health of US military veterans. Here we genotyped 312,571 MVP participants using a custom biobank array and linked the genetic data to laboratory and clinical phenotypes extracted from electronic health records covering a median of 10.0 years of follow-up. Among 297,626 veterans with at least one blood lipid measurement, including 57,332 black and 24,743 Hispanic participants, we tested up to around 32 million variants for association with lipid levels and identified 118 novel genome-wide significant loci after meta-analysis with data from the Global Lipids Genetics Consortium (total n> 600,000). Through a focus on mutations predicted to result in a loss of gene function and a phenome-wide association study, we propose novel indications for pharmaceutical inhibitors targeting PCSK9 (abdominal aortic aneurysm), ANGPTL4 (type 2 diabetes) and PDE3B (triglycerides and coronary disease).

Published
2018
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