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Newly discovered genetic markers help pinpoint diabetes risks, complications

Date:
February 19, 2024
Source:
University of Massachusetts Amherst
Summary:
In the largest genome-wide association study to date on Type 2 diabetes, a team of international researchers has located 1,289 genetic markers associated with Type 2 diabetes (145 of which are newly identified) and generated risk scores for diabetes complications.
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In the largest genome-wide association study to date on Type 2 diabetes, a team of international researchers, co-led by a University of Massachusetts Amherst genetic epidemiologist, has located 1,289 genetic markers associated with Type 2 diabetes (145 of which are newly identified) and generated risk scores for diabetes complications.

In research published Monday, Feb. 19 in the journal Nature that advances understanding into the inheritability of Type 2 diabetes, the scientists used cutting-edge computational approaches to identify eight distinct mechanistic clusters of genetic variants linked to the disease. They also discovered associations between individual clusters and diabetes complications.

"We tried to figure out some of the mechanisms for how these genetic variants are working -- and we did," says co-senior author Cassandra Spracklen, assistant professor of biostatistics and epidemiology in the School of Public Health and Health Sciences.

Ultimately, the goal is to identify potential genetic targets to treat or even cure the chronic metabolic disease that affects and sometimes debilitates more than 400 million adults worldwide, according to the International Diabetes Federation.

The study -- emerging from the newly formed Type 2 Diabetes Global Genomics Initiative -- included data from a highly diverse group of more than 2.5 million individuals, 428,452 of whom have Type 2 diabetes.

"We found eight clusters of Type 2 diabetes-associated variants that have also been associated with other diabetes risk factors -- such as obesity and liver-lipid metabolism -- suggesting the mechanisms for how the variants may be acting to cause diabetes," Spracklen says. "Then we asked if these clusters were also associated with Type 2 diabetes complications? And we found that several of them to also associated with vascular complications, such as coronary artery disease and end-stage diabetic nephropathy."

Even though effective treatments are available for Type 2 diabetes, the option for precision medicine tailored to the individual is still limited. For many people with the disease, treatment strategies still rely on trial and error. Being better able to understand the disease mechanisms will help predict individuals' risk of Type 2 diabetes and allow for earlier intervention.

"We're trying to understand how diabetes develops," says Spracklen, adding that the new research includes data from cohorts not available in an earlier genome-wide association study published in 2022 in Nature Genetics, for which Spracklen was co-first author. "And we're trying to better understand how these genetic variants are actually working within a biological tissue or at the cellular level, which can ultimately lead to new drug targets and treatments."

Senior corresponding author Eleftheria Zeggini, director of the Institute of Translational Genomics at Helmholtz Munich and a professor at the Technical University of Munich, notes that collaboration among scientists is essential for evaluating vast patient data and achieving a comprehensive understanding of genomic risk variants.

"The genetic information in our cells harbors secrets about the risks, progression and complications of many diseases," she says. "Our work leads to an improved understanding of disease-causing biological mechanisms. Better knowledge of progression risk for Type 2 diabetes complications can help put in place early interventions to delay or even prevent these debilitating medical conditions."

The paper concludes, "Our findings … may offer a route to optimize global access to genetically informed diabetes care."


Story Source:

Materials provided by University of Massachusetts Amherst. Note: Content may be edited for style and length.


Journal Reference:

  1. Ken Suzuki, Konstantinos Hatzikotoulas, Lorraine Southam, Henry J. Taylor, Xianyong Yin, Kim M. Lorenz, Ravi Mandla, Alicia Huerta-Chagoya, Giorgio E. M. Melloni, Stavroula Kanoni, Nigel W. Rayner, Ozvan Bocher, Ana Luiza Arruda, Kyuto Sonehara, Shinichi Namba, Simon S. K. Lee, Michael H. Preuss, Lauren E. Petty, Philip Schroeder, Brett Vanderwerff, Mart Kals, Fiona Bragg, Kuang Lin, Xiuqing Guo, Weihua Zhang, Jie Yao, Young Jin Kim, Mariaelisa Graff, Fumihiko Takeuchi, Jana Nano, Amel Lamri, Masahiro Nakatochi, Sanghoon Moon, Robert A. Scott, James P. Cook, Jung-Jin Lee, Ian Pan, Daniel Taliun, Esteban J. Parra, Jin-Fang Chai, Lawrence F. Bielak, Yasuharu Tabara, Yang Hai, Gudmar Thorleifsson, Niels Grarup, Tamar Sofer, Matthias Wuttke, Chloé Sarnowski, Christian Gieger, Darryl Nousome, Stella Trompet, Soo-Heon Kwak, Jirong Long, Meng Sun, Lin Tong, Wei-Min Chen, Suraj S. Nongmaithem, Raymond Noordam, Victor J. Y. Lim, Claudia H. T. Tam, Yoonjung Yoonie Joo, Chien-Hsiun Chen, Laura M. Raffield, Bram Peter Prins, Aude Nicolas, Lisa R. Yanek, Guanjie Chen, Jennifer A. Brody, Edmond Kabagambe, Ping An, Anny H. Xiang, Hyeok Sun Choi, Brian E. Cade, Jingyi Tan, K. Alaine Broadaway, Alice Williamson, Zoha Kamali, Jinrui Cui, Manonanthini Thangam, Linda S. Adair, Adebowale Adeyemo, Carlos A. Aguilar-Salinas, Tarunveer S. Ahluwalia, Sonia S. Anand, Alain Bertoni, Jette Bork-Jensen, Ivan Brandslund, Thomas A. Buchanan, Charles F. Burant, Adam S. Butterworth, Mickaël Canouil, Juliana C. N. Chan, Li-Ching Chang, Miao-Li Chee, Ji Chen, Shyh-Huei Chen, Yuan-Tsong Chen, Zhengming Chen, Lee-Ming Chuang, Mary Cushman, John Danesh, Swapan K. Das, H. Janaka de Silva, George Dedoussis, Latchezar Dimitrov, Ayo P. Doumatey, Shufa Du, Qing Duan, Kai-Uwe Eckardt, Leslie S. Emery, Daniel S. Evans, Michele K. Evans, Krista Fischer, James S. Floyd, Ian Ford, Oscar H. Franco, Timothy M. Frayling, Barry I. Freedman, Pauline Genter, Hertzel C. Gerstein, Vilmantas Giedraitis, Clicerio González-Villalpando, Maria Elena González-Villalpando, Penny Gordon-Larsen, Myron Gross, Lindsay A. Guare, Sophie Hackinger, Liisa Hakaste, Sohee Han, Andrew T. Hattersley, Christian Herder, Momoko Horikoshi, Annie-Green Howard, Willa Hsueh, Mengna Huang, Wei Huang, Yi-Jen Hung, Mi Yeong Hwang, Chii-Min Hwu, Sahoko Ichihara, Mohammad Arfan Ikram, Martin Ingelsson, Md. Tariqul Islam, Masato Isono, Hye-Mi Jang, Farzana Jasmine, Guozhi Jiang, Jost B. Jonas, Torben Jørgensen, Frederick K. Kamanu, Fouad R. Kandeel, Anuradhani Kasturiratne, Tomohiro Katsuya, Varinderpal Kaur, Takahisa Kawaguchi, Jacob M. Keaton, Abel N. Kho, Chiea-Chuen Khor, Muhammad G. Kibriya, Duk-Hwan Kim, Florian Kronenberg, Johanna Kuusisto, Kristi Läll, Leslie A. Lange, Kyung Min Lee, Myung-Shik Lee, Nanette R. Lee, Aaron Leong, Liming Li, Yun Li, Ruifang Li-Gao, Symen Ligthart, Cecilia M. Lindgren, Allan Linneberg, Ching-Ti Liu, Jianjun Liu, Adam E. Locke, Tin Louie, Jian’an Luan, Andrea O. Luk, Xi Luo, Jun Lv, Julie A. Lynch, Valeriya Lyssenko, Shiro Maeda, Vasiliki Mamakou, Sohail Rafik Mansuri, Koichi Matsuda, Thomas Meitinger, Olle Melander, Andres Metspalu, Huan Mo, Andrew D. Morris, Filipe A. Moura, Jerry L. Nadler, Michael A. Nalls, Uma Nayak, Ioanna Ntalla, Yukinori Okada, Lorena Orozco, Sanjay R. Patel, Snehal Patil, Pei Pei, Mark A. Pereira, Annette Peters, Fraser J. Pirie, Hannah G. Polikowsky, Bianca Porneala, Gauri Prasad, Laura J. Rasmussen-Torvik, Alexander P. Reiner, Michael Roden, Rebecca Rohde, Katheryn Roll, Charumathi Sabanayagam, Kevin Sandow, Alagu Sankareswaran, Naveed Sattar, Sebastian Schönherr, Mohammad Shahriar, Botong Shen, Jinxiu Shi, Dong Mun Shin, Nobuhiro Shojima, Jennifer A. Smith, Wing Yee So, Alena Stančáková, Valgerdur Steinthorsdottir, Adrienne M. Stilp, Konstantin Strauch, Kent D. Taylor, Barbara Thorand, Unnur Thorsteinsdottir, Brian Tomlinson, Tam C. Tran, Fuu-Jen Tsai, Jaakko Tuomilehto, Teresa Tusie-Luna, Miriam S. Udler, Adan Valladares-Salgado, Rob M. van Dam, Jan B. van Klinken, Rohit Varma, Niels Wacher-Rodarte, Eleanor Wheeler, Ananda R. Wickremasinghe, Ko Willems van Dijk, Daniel R. Witte, Chittaranjan S. Yajnik, Ken Yamamoto, Kenichi Yamamoto, Kyungheon Yoon, Canqing Yu, Jian-Min Yuan, Salim Yusuf, Matthew Zawistowski, Liang Zhang, Wei Zheng, Stavroula Kanona, David A. van Heel, Leslie J. Raffel, Michiya Igase, Eli Ipp, Susan Redline, Yoon Shin Cho, Lars Lind, Michael A. Province, Myriam Fornage, Craig L. Hanis, Erik Ingelsson, Alan B. Zonderman, Bruce M. Psaty, Ya-Xing Wang, Charles N. Rotimi, Diane M. Becker, Fumihiko Matsuda, Yongmei Liu, Mitsuhiro Yokota, Sharon L. R. Kardia, Patricia A. Peyser, James S. Pankow, James C. Engert, Amélie Bonnefond, Philippe Froguel, James G. Wilson, Wayne H. H. Sheu, Jer-Yuarn Wu, M. Geoffrey Hayes, Ronald C. W. Ma, Tien-Yin Wong, Dennis O. Mook-Kanamori, Tiinamaija Tuomi, Giriraj R. Chandak, Francis S. Collins, Dwaipayan Bharadwaj, Guillaume Paré, Michèle M. Sale, Habibul Ahsan, Ayesha A. Motala, Xiao-Ou Shu, Kyong-Soo Park, J. Wouter Jukema, Miguel Cruz, Yii-Der Ida Chen, Stephen S. Rich, Roberta McKean-Cowdin, Harald Grallert, Ching-Yu Cheng, Mohsen Ghanbari, E-Shyong Tai, Josee Dupuis, Norihiro Kato, Markku Laakso, Anna Köttgen, Woon-Puay Koh, Donald W. Bowden, Colin N. A. Palmer, Jaspal S. Kooner, Charles Kooperberg, Simin Liu, Kari E. North, Danish Saleheen, Torben Hansen, Oluf Pedersen, Nicholas J. Wareham, Juyoung Lee, Bong-Jo Kim, Iona Y. Millwood, Robin G. Walters, Kari Stefansson, Emma Ahlqvist, Mark O. Goodarzi, Karen L. Mohlke, Claudia Langenberg, Christopher A. Haiman, Ruth J. F. Loos, Jose C. Florez, Daniel J. Rader, Marylyn D. Ritchie, Sebastian Zöllner, Reedik Mägi, Nicholas A. Marston, Christian T. Ruff, David A. van Heel, Sarah Finer, Joshua C. Denny, Toshimasa Yamauchi, Takashi Kadowaki, John C. Chambers, Maggie C. Y. Ng, Xueling Sim, Jennifer E. Below, Philip S. Tsao, Kyong-Mi Chang, Mark I. McCarthy, James B. Meigs, Anubha Mahajan, Cassandra N. Spracklen, Josep M. Mercader, Michael Boehnke, Jerome I. Rotter, Marijana Vujkovic, Benjamin F. Voight, Andrew P. Morris, Eleftheria Zeggini. Genetic drivers of heterogeneity in type 2 diabetes pathophysiology. Nature, 2024; DOI: 10.1038/s41586-024-07019-6

Cite This Page:

University of Massachusetts Amherst. "Newly discovered genetic markers help pinpoint diabetes risks, complications." ScienceDaily. ScienceDaily, 19 February 2024. <www.sciencedaily.com/releases/2024/02/240219130910.htm>.
University of Massachusetts Amherst. (2024, February 19). Newly discovered genetic markers help pinpoint diabetes risks, complications. ScienceDaily. Retrieved April 24, 2024 from www.sciencedaily.com/releases/2024/02/240219130910.htm
University of Massachusetts Amherst. "Newly discovered genetic markers help pinpoint diabetes risks, complications." ScienceDaily. www.sciencedaily.com/releases/2024/02/240219130910.htm (accessed April 24, 2024).

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