@article {9172,
	title = {Stroke genetics informs drug discovery and risk prediction across ancestries.},
	journal = {Nature},
	year = {2022},
	month = {2022 Sep 30},
	abstract = {<p>Previous genome-wide association studies (GWASs) of stroke~-~the second leading cause of death worldwide~-~were conducted predominantly in populations of European ancestry. Here, in cross-ancestry GWAS meta-analyses of 110,182 patients who have had a stroke (five ancestries, 33\% non-European) and 1,503,898 control individuals, we identify association signals for stroke and its subtypes at 89 (61 new) independent loci: 60 in primary inverse-variance-weighted analyses and 29 in secondary meta-regression and multitrait analyses. On the basis of internal cross-ancestry validation and an independent follow-up in 89,084 additional cases of stroke (30\% non-European) and 1,013,843 control individuals, 87\% of the primary stroke risk loci and 60\% of the secondary stroke risk loci were replicated (P < 0.05). Effect sizes were highly correlated across ancestries. Cross-ancestry fine-mapping, in silico mutagenesis analysis, and transcriptome-wide and proteome-wide association analyses revealed putative causal genes (such as SH3PXD2A and FURIN) and variants (such as at GRK5 and NOS3). Using a three-pronged approach, we provide genetic evidence for putative drug effects, highlighting F11, KLKB1, PROC, GP1BA, LAMC2 and VCAM1 as possible targets, with drugs already under investigation for stroke for F11 and PROC. A polygenic score integrating cross-ancestry and ancestry-specific stroke GWASs with vascular-risk factor GWASs (integrative polygenic scores) strongly predicted ischaemic stroke in populations of European, East Asian and African ancestry. Stroke genetic risk scores were predictive of ischaemic stroke independent of clinical risk factors in 52,600 clinical-trial participants with cardiometabolic disease. Our results provide insights to inform biology, reveal potential drug targets and derive genetic risk prediction tools across ancestries.</p>},
	issn = {1476-4687},
	doi = {10.1038/s41586-022-05165-3},
	author = {Mishra, Aniket and Malik, Rainer and Hachiya, Tsuyoshi and J{\"u}rgenson, Tuuli and Namba, Shinichi and Posner, Daniel C and Kamanu, Frederick K and Koido, Masaru and Le Grand, Quentin and Shi, Mingyang and He, Yunye and Georgakis, Marios K and Caro, Ilana and Krebs, Kristi and Liaw, Yi-Ching and Vaura, Felix C and Lin, Kuang and Winsvold, Bendik Slagsvold and Srinivasasainagendra, Vinodh and Parodi, Livia and Bae, Hee-Joon and Chauhan, Ganesh and Chong, Michael R and Tomppo, Liisa and Akinyemi, Rufus and Roshchupkin, Gennady V and Habib, Naomi and Jee, Yon Ho and Thomassen, Jesper Qvist and Abedi, Vida and C{\'a}rcel-M{\'a}rquez, Jara and Nygaard, Marianne and Leonard, Hampton L and Yang, Chaojie and Yonova-Doing, Ekaterina and Knol, Maria J and Lewis, Adam J and Judy, Renae L and Ago, Tetsuro and Amouyel, Philippe and Armstrong, Nicole D and Bakker, Mark K and Bartz, Traci M and Bennett, David A and Bis, Joshua C and Bordes, Constance and B{\o}rte, Sigrid and Cain, Anael and Ridker, Paul M and Cho, Kelly and Chen, Zhengming and Cruchaga, Carlos and Cole, John W and De Jager, Phil L and de Cid, Rafael and Endres, Matthias and Ferreira, Leslie E and Geerlings, Mirjam I and Gasca, Natalie C and Gudnason, Vilmundur and Hata, Jun and He, Jing and Heath, Alicia K and Ho, Yuk-Lam and Havulinna, Aki S and Hopewell, Jemma C and Hyacinth, Hyacinth I and Inouye, Michael and Jacob, Mina A and Jeon, Christina E and Jern, Christina and Kamouchi, Masahiro and Keene, Keith L and Kitazono, Takanari and Kittner, Steven J and Konuma, Takahiro and Kumar, Amit and Lacaze, Paul and Launer, Lenore J and Lee, Keon-Joo and Lepik, Kaido and Li, Jiang and Li, Liming and Manichaikul, Ani and Markus, Hugh S and Marston, Nicholas A and Meitinger, Thomas and Mitchell, Braxton D and Montellano, Felipe A and Morisaki, Takayuki and Mosley, Thomas H and Nalls, Mike A and Nordestgaard, B{\o}rge G and O{\textquoteright}Donnell, Martin J and Okada, Yukinori and Onland-Moret, N Charlotte and Ovbiagele, Bruce and Peters, Annette and Psaty, Bruce M and Rich, Stephen S and Rosand, Jonathan and Sabatine, Marc S and Sacco, Ralph L and Saleheen, Danish and Sandset, Else Charlotte and Salomaa, Veikko and Sargurupremraj, Muralidharan and Sasaki, Makoto and Satizabal, Claudia L and Schmidt, Carsten O and Shimizu, Atsushi and Smith, Nicholas L and Sloane, Kelly L and Sutoh, Yoichi and Sun, Yan V and Tanno, Kozo and Tiedt, Steffen and Tatlisumak, Turgut and Torres-Aguila, Nuria P and Tiwari, Hemant K and Tr{\'e}gou{\"e}t, David-Alexandre and Trompet, Stella and Tuladhar, Anil Man and Tybj{\ae}rg-Hansen, Anne and van Vugt, Marion and Vibo, Riina and Verma, Shefali S and Wiggins, Kerri L and Wennberg, Patrik and Woo, Daniel and Wilson, Peter W F and Xu, Huichun and Yang, Qiong and Yoon, Kyungheon and Millwood, Iona Y and Gieger, Christian and Ninomiya, Toshiharu and Grabe, Hans J and Jukema, J Wouter and Rissanen, Ina L and Strbian, Daniel and Kim, Young Jin and Chen, Pei-Hsin and Mayerhofer, Ernst and Howson, Joanna M M and Irvin, Marguerite R and Adams, Hieab and Wassertheil-Smoller, Sylvia and Christensen, Kaare and Ikram, Mohammad A and Rundek, Tatjana and Worrall, Bradford B and Lathrop, G Mark and Riaz, Moeen and Simonsick, Eleanor M and K{\~o}rv, Janika and Fran{\c c}a, Paulo H C and Zand, Ramin and Prasad, Kameshwar and Frikke-Schmidt, Ruth and de Leeuw, Frank-Erik and Liman, Thomas and Haeusler, Karl Georg and Ruigrok, Ynte M and Heuschmann, Peter Ulrich and Longstreth, W T and Jung, Keum Ji and Bastarache, Lisa and Par{\'e}, Guillaume and Damrauer, Scott M and Chasman, Daniel I and Rotter, Jerome I and Anderson, Christopher D and Zwart, John-Anker and Niiranen, Teemu J and Fornage, Myriam and Liaw, Yung-Po and Seshadri, Sudha and Fernandez-Cadenas, Israel and Walters, Robin G and Ruff, Christian T and Owolabi, Mayowa O and Huffman, Jennifer E and Milani, Lili and Kamatani, Yoichiro and Dichgans, Martin and Debette, Stephanie}
}
@article {9910,
	title = {Genome-wide association study meta-analysis provides insights into the etiology of heart failure and its subtypes.},
	journal = {Nat Genet},
	year = {2025},
	month = {2025 Mar 04},
	abstract = {<p>Heart failure (HF) is a major contributor to global morbidity and mortality. While distinct clinical subtypes, defined by etiology and left ventricular ejection fraction, are well recognized, their genetic determinants remain inadequately understood. In this study, we report a genome-wide association study of HF and its subtypes in a sample of 1.9 million individuals. A total of 153,174 individuals had HF, of whom 44,012 had a nonischemic etiology (ni-HF). A subset of patients with ni-HF were stratified based on left ventricular systolic function, where data were available, identifying 5,406 individuals with reduced ejection fraction and 3,841 with preserved ejection fraction. We identify 66 genetic loci associated with HF and its subtypes, 37 of which have not previously been reported. Using functionally informed gene prioritization methods, we predict effector genes for each identified locus, and map these to etiologic disease clusters through phenome-wide association analysis, network analysis and colocalization. Through heritability enrichment analysis, we highlight the role of extracardiac tissues in disease etiology. We then examine the differential associations of upstream risk factors with HF subtypes using Mendelian randomization. These findings extend our understanding of the mechanisms underlying HF etiology and may inform future approaches to prevention and treatment.</p>},
	issn = {1546-1718},
	doi = {10.1038/s41588-024-02064-3},
	author = {Henry, Albert and Mo, Xiaodong and Finan, Chris and Chaffin, Mark D and Speed, Doug and Issa, Hanane and Denaxas, Spiros and Ware, James S and Zheng, Sean L and M{\"a}larstig, Anders and Gratton, Jasmine and Bond, Isabelle and Roselli, Carolina and Miller, David and Chopade, Sandesh and Schmidt, A Floriaan and Abner, Erik and Adams, Lance and Andersson, Charlotte and Aragam, Krishna G and Arnl{\"o}v, Johan and Asselin, Geraldine and Raja, Anna Axelsson and Backman, Joshua D and Bartz, Traci M and Biddinger, Kiran J and Biggs, Mary L and Bloom, Heather L and Boersma, Eric and Brandimarto, Jeffrey and Brown, Michael R and Brunak, S{\o}ren and Bruun, Mie Topholm and Buckbinder, Leonard and Bundgaard, Henning and Carey, David J and Chasman, Daniel I and Chen, Xing and Cook, James P and Czuba, Tomasz and de Denus, Simon and Dehghan, Abbas and Delgado, Graciela E and Doney, Alexander S and D{\"o}rr, Marcus and Dowsett, Joseph and Dudley, Samuel C and Engstr{\"o}m, Gunnar and Erikstrup, Christian and Esko, T{\~o}nu and Farber-Eger, Eric H and Felix, Stephan B and Finer, Sarah and Ford, Ian and Ghanbari, Mohsen and Ghasemi, Sahar and Ghouse, Jonas and Giedraitis, Vilmantas and Giulianini, Franco and Gottdiener, John S and Gross, Stefan and Gu{\dh}bjartsson, Dan{\'\i}el F and Gui, Hongsheng and Gutmann, Rebecca and H{\"a}gg, Sara and Haggerty, Christopher M and Hedman, {\r A}sa K and Helgadottir, Anna and Hemingway, Harry and Hillege, Hans and Hyde, Craig L and Aagaard Jensen, Bitten and Jukema, J Wouter and Kardys, Isabella and Karra, Ravi and Kavousi, Maryam and Kizer, Jorge R and Kleber, Marcus E and K{\o}ber, Lars and Koekemoer, Andrea and Kuchenbaecker, Karoline and Lai, Yi-Pin and Lanfear, David and Langenberg, Claudia and Lin, Honghuang and Lind, Lars and Lindgren, Cecilia M and Liu, Peter P and London, Barry and Lowery, Brandon D and Luan, Jian{\textquoteright}an and Lubitz, Steven A and Magnusson, Patrik and Margulies, Kenneth B and Marston, Nicholas A and Martin, Hilary and M{\"a}rz, Winfried and Melander, Olle and Mordi, Ify R and Morley, Michael P and Morris, Andrew P and Morrison, Alanna C and Morton, Lori and Nagle, Michael W and Nelson, Christopher P and Niessner, Alexander and Niiranen, Teemu and Noordam, Raymond and Nowak, Christoph and O{\textquoteright}Donoghue, Michelle L and Ostrowski, Sisse Rye and Owens, Anjali T and Palmer, Colin N A and Par{\'e}, Guillaume and Pedersen, Ole Birger and Perola, Markus and Pigeyre, Marie and Psaty, Bruce M and Rice, Kenneth M and Ridker, Paul M and Romaine, Simon P R and Rotter, Jerome I and Ruff, Christian T and Sabatine, Marc S and Sallah, Neneh and Salomaa, Veikko and Sattar, Naveed and Shalaby, Alaa A and Shekhar, Akshay and Smelser, Diane T and Smith, Nicholas L and S{\o}rensen, Erik and Srinivasan, Sundararajan and Stefansson, Kari and Sveinbj{\"o}rnsson, Gar{\dh}ar and Svensson, Per and Tammesoo, Mari-Liis and Tardif, Jean-Claude and Teder-Laving, Maris and Teumer, Alexander and Thorgeirsson, Gu{\dh}mundur and Thorsteinsdottir, Unnur and Torp-Pedersen, Christian and Tragante, Vinicius and Trompet, Stella and Uitterlinden, Andr{\'e} G and Ullum, Henrik and van der Harst, Pim and van Heel, David and van Setten, Jessica and van Vugt, Marion and Veluchamy, Abirami and Verschuuren, Monique and Verweij, Niek and Vissing, Christoffer Rasmus and V{\"o}lker, Uwe and Voors, Adriaan A and Wallentin, Lars and Wang, Yunzhang and Weeke, Peter E and Wiggins, Kerri L and Williams, L Keoki and Yang, Yifan and Yu, Bing and Zannad, Faiez and Zheng, Chaoqun and Asselbergs, Folkert W and Cappola, Thomas P and Dub{\'e}, Marie-Pierre and Dunn, Michael E and Lang, Chim C and Samani, Nilesh J and Shah, Svati and Vasan, Ramachandran S and Smith, J Gustav and Holm, Hilma and Shah, Sonia and Ellinor, Patrick T and Hingorani, Aroon D and Wells, Quinn and Lumbers, R Thomas}
}
