@article {9619,
	title = {Genetic drivers of heterogeneity in type 2 diabetes pathophysiology.},
	journal = {Nature},
	year = {2024},
	month = {2024 Feb 19},
	abstract = {<p>Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes and molecular mechanisms that are often specific to cell type. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7\% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 {\texttimes} 10) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.</p>},
	issn = {1476-4687},
	doi = {10.1038/s41586-024-07019-6},
	author = {Suzuki, Ken and Hatzikotoulas, Konstantinos and Southam, Lorraine and Taylor, Henry J and Yin, Xianyong and Lorenz, Kim M and Mandla, Ravi and Huerta-Chagoya, Alicia and Melloni, Giorgio E M and Kanoni, Stavroula and Rayner, Nigel W and Bocher, Ozvan and Arruda, Ana Luiza and Sonehara, Kyuto and Namba, Shinichi and Lee, Simon S K and Preuss, Michael H and Petty, Lauren E and Schroeder, Philip and Vanderwerff, Brett and Kals, Mart and Bragg, Fiona and Lin, Kuang and Guo, Xiuqing and Zhang, Weihua and Yao, Jie and Kim, Young Jin and Graff, Mariaelisa and Takeuchi, Fumihiko and Nano, Jana and Lamri, Amel and Nakatochi, Masahiro and Moon, Sanghoon and Scott, Robert A and Cook, James P and Lee, Jung-Jin and Pan, Ian and Taliun, Daniel and Parra, Esteban J and Chai, Jin-Fang and Bielak, Lawrence F and Tabara, Yasuharu and Hai, Yang and Thorleifsson, Gudmar and Grarup, Niels and Sofer, Tamar and Wuttke, Matthias and Sarnowski, Chloe and Gieger, Christian and Nousome, Darryl and Trompet, Stella and Kwak, Soo-Heon and Long, Jirong and Sun, Meng and Tong, Lin and Chen, Wei-Min and Nongmaithem, Suraj S and Noordam, Raymond and Lim, Victor J Y and Tam, Claudia H T and Joo, Yoonjung Yoonie and Chen, Chien-Hsiun and Raffield, Laura M and Prins, Bram Peter and Nicolas, Aude and Yanek, Lisa R and Chen, Guanjie and Brody, Jennifer A and Kabagambe, Edmond and An, Ping and Xiang, Anny H and Choi, Hyeok Sun and Cade, Brian E and Tan, Jingyi and Broadaway, K Alaine and Williamson, Alice and Kamali, Zoha and Cui, Jinrui and Thangam, Manonanthini and Adair, Linda S and Adeyemo, Adebowale and Aguilar-Salinas, Carlos A and Ahluwalia, Tarunveer S and Anand, Sonia S and Bertoni, Alain and Bork-Jensen, Jette and Brandslund, Ivan and Buchanan, Thomas A and Burant, Charles F and Butterworth, Adam S and Canouil, Micka{\"e}l and Chan, Juliana C N and Chang, Li-Ching and Chee, Miao-Li and Chen, Ji and Chen, Shyh-Huei and Chen, Yuan-Tsong and Chen, Zhengming and Chuang, Lee-Ming and Cushman, Mary and Danesh, John and Das, Swapan K and de Silva, H Janaka and Dedoussis, George and Dimitrov, Latchezar and Doumatey, Ayo P and Du, Shufa and Duan, Qing and Eckardt, Kai-Uwe and Emery, Leslie S and Evans, Daniel S and Evans, Michele K and Fischer, Krista and Floyd, James S and Ford, Ian and Franco, Oscar H and Frayling, Timothy M and Freedman, Barry I and Genter, Pauline and Gerstein, Hertzel C and Giedraitis, Vilmantas and Gonz{\'a}lez-Villalpando, Clicerio and Gonzalez-Villalpando, Maria Elena and Gordon-Larsen, Penny and Gross, Myron and Guare, Lindsay A and Hackinger, Sophie and Hakaste, Liisa and Han, Sohee and Hattersley, Andrew T and Herder, Christian and Horikoshi, Momoko and Howard, Annie-Green and Hsueh, Willa and Huang, Mengna and Huang, Wei and Hung, Yi-Jen and Hwang, Mi Yeong and Hwu, Chii-Min and Ichihara, Sahoko and Ikram, Mohammad Arfan and Ingelsson, Martin and Islam, Md Tariqul and Isono, Masato and Jang, Hye-Mi and Jasmine, Farzana and Jiang, Guozhi and Jonas, Jost B and J{\o}rgensen, Torben and Kamanu, Frederick K and Kandeel, Fouad R and Kasturiratne, Anuradhani and Katsuya, Tomohiro and Kaur, Varinderpal and Kawaguchi, Takahisa and Keaton, Jacob M and Kho, Abel N and Khor, Chiea-Chuen and Kibriya, Muhammad G and Kim, Duk-Hwan and Kronenberg, Florian and Kuusisto, Johanna and L{\"a}ll, Kristi and Lange, Leslie A and Lee, Kyung Min and Lee, Myung-Shik and Lee, Nanette R and Leong, Aaron and Li, Liming and Li, Yun and Li-Gao, Ruifang and Ligthart, Symen and Lindgren, Cecilia M and Linneberg, Allan and Liu, Ching-Ti and Liu, Jianjun and Locke, Adam E and Louie, Tin and Luan, Jian{\textquoteright}an and Luk, Andrea O and Luo, Xi and Lv, Jun and Lynch, Julie A and Lyssenko, Valeriya and Maeda, Shiro and Mamakou, Vasiliki and Mansuri, Sohail Rafik and Matsuda, Koichi and Meitinger, Thomas and Melander, Olle and Metspalu, Andres and Mo, Huan and Morris, Andrew D and Moura, Filipe A and Nadler, Jerry L and Nalls, Michael A and Nayak, Uma and Ntalla, Ioanna and Okada, Yukinori and Orozco, Lorena and Patel, Sanjay R and Patil, Snehal and Pei, Pei and Pereira, Mark A and Peters, Annette and Pirie, Fraser J and Polikowsky, Hannah G and Porneala, Bianca and Prasad, Gauri and Rasmussen-Torvik, Laura J and Reiner, Alexander P and Roden, Michael and Rohde, Rebecca and Roll, Katheryn and Sabanayagam, Charumathi and Sandow, Kevin and Sankareswaran, Alagu and Sattar, Naveed and Sch{\"o}nherr, Sebastian and Shahriar, Mohammad and Shen, Botong and Shi, Jinxiu and Shin, Dong Mun and Shojima, Nobuhiro and Smith, Jennifer A and So, Wing Yee and Stan{\v c}{\'a}kov{\'a}, Alena and Steinthorsdottir, Valgerdur and Stilp, Adrienne M and Strauch, Konstantin and Taylor, Kent D and Thorand, Barbara and Thorsteinsdottir, Unnur and Tomlinson, Brian and Tran, Tam C and Tsai, Fuu-Jen and Tuomilehto, Jaakko and Tusi{\'e}-Luna, Teresa and Udler, Miriam S and Valladares-Salgado, Adan and van Dam, Rob M and van Klinken, Jan B and Varma, Rohit and Wacher-Rodarte, Niels and Wheeler, Eleanor and Wickremasinghe, Ananda R and van Dijk, Ko Willems and Witte, Daniel R and Yajnik, Chittaranjan S and Yamamoto, Ken and Yamamoto, Kenichi and Yoon, Kyungheon and Yu, Canqing and Yuan, Jian-Min and Yusuf, Salim and Zawistowski, Matthew and Zhang, Liang and Zheng, Wei and Raffel, Leslie J and Igase, Michiya and Ipp, Eli and Redline, Susan and Cho, Yoon Shin and Lind, Lars and Province, Michael A and Fornage, Myriam and Hanis, Craig L and Ingelsson, Erik and Zonderman, Alan B and Psaty, Bruce M and Wang, Ya-Xing and Rotimi, Charles N and Becker, Diane M and Matsuda, Fumihiko and Liu, Yongmei and Yokota, Mitsuhiro and Kardia, Sharon L R and Peyser, Patricia A and Pankow, James S and Engert, James C and Bonnefond, Am{\'e}lie and Froguel, Philippe and Wilson, James G and Sheu, Wayne H H and Wu, Jer-Yuarn and Hayes, M Geoffrey and Ma, Ronald C W and Wong, Tien-Yin and Mook-Kanamori, Dennis O and Tuomi, Tiinamaija and Chandak, Giriraj R and Collins, Francis S and Bharadwaj, Dwaipayan and Par{\'e}, Guillaume and Sale, Mich{\`e}le M and Ahsan, Habibul and Motala, Ayesha A and Shu, Xiao-Ou and Park, Kyong-Soo and Jukema, J Wouter and Cruz, Miguel and Chen, Yii-Der Ida and Rich, Stephen S and McKean-Cowdin, Roberta and Grallert, Harald and Cheng, Ching-Yu and Ghanbari, Mohsen and Tai, E-Shyong and Dupuis, Jos{\'e}e and Kato, Norihiro and Laakso, Markku and K{\"o}ttgen, Anna and Koh, Woon-Puay and Bowden, Donald W and Palmer, Colin N A and Kooner, Jaspal S and Kooperberg, Charles and Liu, Simin and North, Kari E and Saleheen, Danish and Hansen, Torben and Pedersen, Oluf and Wareham, Nicholas J and Lee, Juyoung and Kim, Bong-Jo and Millwood, Iona Y and Walters, Robin G and Stefansson, Kari and Ahlqvist, Emma and Goodarzi, Mark O and Mohlke, Karen L and Langenberg, Claudia and Haiman, Christopher A and Loos, Ruth J F and Florez, Jose C and Rader, Daniel J and Ritchie, Marylyn D and Z{\"o}llner, Sebastian and M{\"a}gi, Reedik and Marston, Nicholas A and Ruff, Christian T and van Heel, David A and Finer, Sarah and Denny, Joshua C and Yamauchi, Toshimasa and Kadowaki, Takashi and Chambers, John C and Ng, Maggie C Y and Sim, Xueling and Below, Jennifer E and Tsao, Philip S and Chang, Kyong-Mi and McCarthy, Mark I and Meigs, James B and Mahajan, Anubha and Spracklen, Cassandra N and Mercader, Josep M and Boehnke, Michael and Rotter, Jerome I and Vujkovic, Marijana and Voight, Benjamin F and Morris, Andrew P and Zeggini, Eleftheria}
}
@article {9914,
	title = {Meta-analysis of genome-wide associations and polygenic risk prediction for atrial fibrillation in more than 180,000 cases.},
	journal = {Nat Genet},
	volume = {57},
	year = {2025},
	month = {2025 Mar},
	pages = {539-547},
	abstract = {<p>Atrial fibrillation (AF) is the most common heart rhythm abnormality and is a leading cause of heart failure and stroke. This large-scale meta-analysis of genome-wide association studies increased the power to detect single-nucleotide variant associations and found more than 350 AF-associated genetic loci. We identified candidate genes related to muscle contractility, cardiac muscle development and cell-cell communication at 139 loci. Furthermore, we assayed chromatin accessibility using assay for transposase-accessible chromatin with sequencing and histone H3 lysine 4 trimethylation in stem cell-derived atrial cardiomyocytes. We observed a marked increase in chromatin accessibility for our sentinel variants and prioritized genes in atrial cardiomyocytes. Finally, a polygenic risk score (PRS) based on our updated effect estimates improved AF risk prediction compared to the CHARGE-AF clinical risk score and a previously reported PRS for AF. The doubling of known risk loci will facilitate a greater understanding of the pathways underlying AF.</p>},
	keywords = {Atrial Fibrillation, Chromatin, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Multifactorial Inheritance, Myocytes, Cardiac, Polymorphism, Single Nucleotide, Risk Factors},
	issn = {1546-1718},
	doi = {10.1038/s41588-024-02072-3},
	author = {Roselli, Carolina and Surakka, Ida and Olesen, Morten S and Sveinbjornsson, Gardar and Marston, Nicholas A and Choi, Seung Hoan and Holm, Hilma and Chaffin, Mark and Gudbjartsson, Daniel and Hill, Matthew C and Aegisdottir, Hildur and Albert, Christine M and Alonso, Alvaro and Anderson, Christopher D and Arking, Dan E and Arnar, David O and Barnard, John and Benjamin, Emelia J and Braunwald, Eugene and Brumpton, Ben and Campbell, Archie and Chami, Nathalie and Chasman, Daniel I and Cho, Kelly and Choi, Eue-Keun and Christophersen, Ingrid E and Chung, Mina K and Conen, David and Crijns, Harry J and Cutler, Michael J and Czuba, Tomasz and Damrauer, Scott M and Dichgans, Martin and D{\"o}rr, Marcus and Dudink, Elton and Duong, ThuyVy and Erikstrup, Christian and Esko, T{\~o}nu and Fatkin, Diane and Faul, Jessica D and Ferreira, Manuel and Freitag, Daniel F and Ganesh, Santhi K and Gaziano, J Michael and Geelhoed, Bastiaan and Ghouse, Jonas and Gieger, Christian and Giulianini, Franco and Graham, Sarah E and Gudnason, Vilmundur and Guo, Xiuqing and Haggerty, Christopher and Hayward, Caroline and Heckbert, Susan R and Hveem, Kristian and Ito, Kaoru and Johnson, Renee and Jukema, J Wouter and Jurgens, Sean J and K{\"a}{\"a}b, Stefan and Kane, John P and Kany, Shinwan and Kardia, Sharon L R and Kavousi, Maryam and Khurshid, Shaan and Kamanu, Frederick K and Kirchhof, Paulus and Kleber, Marcus E and Knight, Stacey and Komuro, Issei and Krieger, Jose E and Launer, Lenore J and Li, Dadong and Lin, Honghuang and Lin, Henry J and Loos, Ruth J F and Lotta, Luca and Lubitz, Steven A and Lunetta, Kathryn L and Macfarlane, Peter W and Magnusson, Patrik K E and Malik, Rainer and Mantineo, Helene and Marcus, Gregory M and M{\"a}rz, Winfried and McManus, David D and Melander, Olle and Melloni, Giorgio E M and Meyre, Pascal B and Miyazawa, Kazuo and Mohanty, Sanghamitra and Monfort, Laia M and M{\"u}ller-Nurasyid, Martina and Nafissi, Navid A and Natale, Andrea and Nazarian, Saman and Ostrowski, Sisse R and Pak, Hui-Nam and Pang, Shichao and Pedersen, Ole B and Pedersen, Nancy L and Pereira, Alexandre C and Pirruccello, James P and Preuss, Michael and Psaty, Bruce M and Pullinger, Clive R and Rader, Daniel J and R{\"a}m{\"o}, Joel T and Ridker, Paul M and Rienstra, Michiel and Risch, Lorenz and Roden, Dan M and Rotter, Jerome I and Sabatine, Marc S and Schunkert, Heribert and Shah, Svati H and Shim, Jaemin and Shoemaker, M Benjamin and Simonson, Bridget and Sinner, Moritz F and Smit, Roelof A J and Smith, Jennifer A and Smith, Nicholas L and Smith, J Gustav and Soliman, Elsayed Z and S{\o}rensen, Erik and Sotoodehnia, Nona and Strbian, Daniel and Stricker, Bruno H and Teder-Laving, Maris and Sun, Yan V and Th{\'e}riault, S{\'e}bastien and Thorolfsdottir, Rosa B and Thorsteinsdottir, Unnur and Tveit, Arnljot and van der Harst, Pim and van Meurs, Joyce and Wang, Biqi and Weiss, Stefan and Wells, Quinn S and Weng, Lu-Chen and Wilson, Peter W and Xiao, Ling and Yang, Pil-Sung and Yao, Jie and Yoneda, Zachary T and Zeller, Tanja and Zeng, Lingyao and Zhao, Wei and Zhou, Xiang and Z{\"o}llner, Sebastian and Ruff, Christian T and Bundgaard, Henning and Willer, Cristen and Stefansson, Kari and Ellinor, Patrick T}
}
