Medicine
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This repository contains the published and unpublished research of the Faculty of Medicine by the staff members of the faculty
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Item The Trans-ancestral genomic architecture of glycemic traits(Nature Pub. Co., 2021) Chen, J.; Spracklen, C.N.; Marenne, G.; Varshney, A.; Corbin, L.J.; Luan, J.; Willems, S.M.; Wu, Y.; Zhang, X.; Horikoshi, M.; Boutin, T.S.; Mägi, R.; Waage, J.; Li-Gao, R.; Chan, K.H.K; Yao, J.; Anasanti, M.D.; Chu, A.Y.; Claringbould, A.; Heikkinen, J.; Hong, J.; Hottenga, J.J.; Huo, S.; Kaakinen, M.A.; Louie, T.; März, W.; Moreno-Macias, H.; Ndungu, A.; Nelson, S.C.; Nolte, I.M.; North, K.E.; Raulerson, C.K.; Ray, D.; Rohde, R.; Rybin, D.; Schurmann, C.; Sim, X.; Southam, L.; Stewart, I.D.; Wang, C.A.; Wang, Y.; Wu, P.; Zhang, W.; Ahluwalia, T.S.; Appel, E.V.R.; Bielak, L.F.; Brody, J.A.; Burtt, N.P.; Cabrera, C.P.; Cade, B.E.; Chai, J.F.; Chai, X.; Chang, L.C.; Chen, C.H.; Chen, B.H.; Chitrala, K.N.; Chiu, Y.F.; De Haan, H.G.; Delgado, G.E.; Demirkan, A.; Duan, Q.; Engmann, J.; Fatumo, S.A.; Gayán, J.; Giulianini, F.; Gong, J.H.; Gustafsson, S.; Hai, Y.; Hartwig, F.P.; He, J.; Heianza, Y.; Huang, T.; Huerta-Chagoya, A.; Hwang, M.Y.; Jensen, R.A.; Kawaguchi, T.; Kentistou, K.A.; Kim, Y.J.; Kleber, M.E.; Kooner, I.K.; Lai, S.; Lange, L.A.; Langefeld, C.D.; Lauzon, M.; Li, M.; Ligthart, S.; Liu, J.; Loh, M.; Long, J.; Lyssenko, V.; Mangino, M.; Marzi, C.; Montasser, M.E.; Nag, A.; Nakatochi, M.; Noce, D.; Noordam, R.; Pistis, G.; Preuss, M.; Raffield, L.; Rasmussen-Torvik, L.J.; Rich, S.S.; Robertson, N.R.; Rueedi, R.; Ryan, K.; Sanna, S.; Saxena, R.; Schraut, K.E.; Sennblad, B.; Setoh, K.; Smith, A.V.; Sparsø, T.; Strawbridge, R.J.; Takeuchi, F.; Tan, J.; Trompet, S.; Van den Akker, E.; Van der Most, P.J.; Verweij, N.; Vogel, M.; Wang, H.; Wang, C.; Wang, N.; Warren, H.R.; Wen, W.; Wilsgaard, T.; Wong, A.; Wood, A.R.; Xie, T.; Zafarmand, M.H.; Zhao, J.H.; Zhao, W.; Amin, N.; Arzumanyan, Z.; Astrup, A.; Bakker, S.J.L.; Baldassarre, D.; Beekman, M.; Bergman, R.N.; Bertoni, A.; Blüher, M.; Bonnycastle, L.L.; Bornstein, S.R.; Bowden, D.W.; Cai, Q.; Campbell, A.; Campbell, H.; Chang, Y.C.; de Geus, E.J.C.; Dehghan, A.; Du, S.; Eiriksdottir, G.; Farmaki, A.E.; Frånberg, M.; Fuchsberger, C.; Gao, Y.; Gjesing, A.P.; Goel, A.; Han, S.; Hartman, C.A.; Herder, C.; Hicks, A.A.; Hsieh, C.H.; Hsueh, W.A.; Ichihara, S.; Igase, M.; Ikram, M.A.; Johnson, W.C.; Jørgensen, M.E.; Joshi, P.K.; Kalyani, R.R.; Kandeel, F.R.; Katsuya, T.; Khor, C.C.; Kiess, W.; Kolcic, I.; Kuulasmaa, T.; Kuusisto, J.; Läll, K.; Lam, K.; Lawlor, D.A.; Lee, N.R.; Lemaitre, R.N.; Li, H.; Lifelines Cohort Study; Lin, S.Y.; Lindström, J.; Linneberg, A.; Liu, J.; Lorenzo, C.; Matsubara, T.; Matsuda, F.; Mingrone, G.; Mooijaart, S.; Moon, S.; Nabika, T.; Nadkarni, G.N.; Nadler, J.L.; Nelis, M.; Neville, M.J.; Norris, J.M.; Ohyagi, Y.; Peters, A.; Peyser, P.A.; Polasek, O.; Qi, Q.; Raven, D.; Reilly, D.F.; Reiner, A.; Rivideneira, F.; Roll, K.; Rudan, I.; Sabanayagam, C.; Sandow, K.; Sattar, N.; Schürmann, A.; Shi, J.; Stringham, H.M.; Taylor, K.D.; Teslovich, T.M.; Thuesen, B.; Timmers, P.R.H.J.; Tremoli, E.; Tsai, M.Y.; Uitterlinden, A.; van Dam, R.M.; van Heemst, D.; van Hylckama Vlieg, A.; van Vliet-Ostaptchouk, J.V.; Vangipurapu, J.; Vestergaard, H.; Wang, T.; Willems van Dijk, K.; Zemunik, T.; Abecasis, G.R.; Adair, L.S.; Aguilar-Salinas, C.A.; Alarcón-Riquelme, M.E.; An, P.; Aviles-Santa, L.; Becker, D.M.; Beilin, L.J.; Bergmann, S.; Bisgaard, H.; Black, C.; Boehnke, M.; Boerwinkle, E.; Böhm, B.O.; Bønnelykke, K.; Boomsma, D.I.; Bottinger, E.P.; Buchanan, T.A.; Canouil, M.; Caulfield, M.J.; Chambers, J.C.; Chasman, D.I.; Chen, Y.I.; Cheng, C.Y.; Collins, F.S.; Correa, A.; Cucca, F.; de Silva, H.J.; Dedoussis, G.; Elmståhl, S.; Evans, M.K.; Ferrannini, E.; Ferrucci, L.; Florez, J.C.; Franks, P.W.; Frayling, T.M.; Froguel, P.; Gigante, B.; Goodarzi, M.O.; Gordon-Larsen, P.; Grallert, H.; Grarup, N.; Grimsgaard, S.; Groop, L.; Gudnason, V.; Guo, X.; Hamsten, A.; Hansen, T.; Hayward, C.; Heckbert, S.R.; Horta, B.L.; Huang, W.; Ingelsson, E.; James, P.S.; Jarvelin, M.R.; Jonas, J.B.; Jukema, J.W.; Kaleebu, P.; Kaplan, R.; Kardia, S.L.R.; Kato, N.; Keinanen-Kiukaanniemi, S.M.; Kim, B.J.; Kivimaki, M.; Koistinen, H.A.; Kooner, J.S.; Körner, A.; Kovacs, P.; Kuh, D.; Kumari, M.; Kutalik, Z.; Laakso, M.; Lakka, T.A.; Launer, L.J.; Leander, K.; Li, H.; Lin, X.; Lind, L.; Lindgren, C.; Liu, S.; Loos, R.J.F.; Magnusson, P.K.E.; Mahajan, A.; Metspalu, A.; Mook-Kanamori, D.O.; Mori, T.A.; Munroe, P.B.; Njølstad, I.; O'Connell, J.R.; Oldehinkel, A.J.; Ong, K.K.; Padmanabhan, S.; Palmer, C.N.A.; Palmer, N.D.; Pedersen, O.; Pennell, C.E.; Porteous, D.J.; Pramstaller, P.P.; Province, M.A.; Psaty, B.M.; Qi, L.; Raffel, L.J.; Rauramaa, R.; Redline, S.; Ridker, P.M.; Rosendaal, F.R.; Saaristo, T.E.; Sandhu, M.; Saramies, J.; Schneiderman, N.; Schwarz, P.; Scott, L.J.; Selvin, E.; Sever, P.; Shu, X.O.; Slagboom, P.E.; Small, K.S.; Smith, B.H.; Snieder, H.; Sofer, T.; Sørensen, T.I.A.; Spector, T.D.; Stanton, A.; Steves, C.J.; Stumvoll, M.; Sun, L.; Tabara, Y.; Tai, E.S.; Timpson, N.J.; Tönjes, A.; Tuomilehto, J.; Tusie, T.; Uusitupa, M.; van der Harst, P.; van Duijn, C.; Vitart, V.; Vollenweider, P.; Vrijkotte, T.G.M.; Wagenknecht, L.E.; Walker, M.; Wang, Y.X.; Wareham, N.J.; Watanabe, R.M.; Watkins, H.; Wei, W.B.; Wickremasinghe, A.R.; Willemsen, G.; Wilson, J.F.; Wong, T.Y.; Wu, J.Y.; Xiang, A.H.; Yanek, L.R.; Yengo, L.; Yokota, M.; Zeggini, E.; Zheng, W.; Zonderman, A.B.; Rotter, J.I.; Gloyn, A.L.; McCarthy, M.I.; Dupuis, J.; Meigs, J.B.; Scott, R.A.; Prokopenko, I.; Leong, A.; Liu, C.T.; Parker, S.C.J.; Mohlke, K.L.; Langenberg, C.; Wheeler, E.; Morris, A.P.; Barroso, I.; Meta-Analysis of Glucose and Insulin-related Traits Consortium (MAGIC) Collaborators.ABSTRACT: Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10-8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.Item Gene-educational attainment interactions in a multi-ancestry genome-wide meta-analysis identify novel blood pressure loci(Stockton Press., 2021) de Las Fuentes, L.; Sung, Y. J.; Noordam, R.; Winkler, T.; Feitosa, M.F.; Schwander, K.; Bentley, A.R.; Brown, M.R.; Guo, X.; Manning, A.; Chasman, D.I.; Aschard, H.; Bartz, T. M.; Bielak, L.F.; Campbell, A.; Cheng, C.Y.; Dorajoo, R.; Hartwig, F. P.; Horimoto, A.R.V.R.; Li, C.; Li-Gao, R.; Liu, Y.; Marten, J.; Musani, S.K.; Ntalla, I.; Rankinen, T.; Richard, M.; Sim, X.; Smith, A.V.; Tajuddin, S.M.; Tayo, B.O.; Vojinovic, D.; Warren, H.R.; Xuan, D.; Alver, M.; Boissel, M.; Chai, J.F.; Chen, X.; Christensen, K.; Divers, J.; Evangelou, E.; Gao, C.; Girotto, G.; Harris, S.E.; He, M.; Hsu, F.C.; Kühnel, B.; Laguzzi, F.; Li, X.; Lyytikäinen, L. P.; Nolte, I. M.; Poveda, A.; Rauramaa, R.; Riaz, M.; Rueedi, R.; Shu, X.O.; Snieder, H.; Sofer, T.; Takeuchi, F.; Verweij, N.; Ware, E.B.; Weiss, S.; Yanek, L.R.; Amin, N.; Arking, D.E.; Arnett, D.K.; Bergmann, S.; Boerwinkle, E.; Brody, J.A.; Broeckel, U.; Brumat, M.; Burke, G.; Cabrera, C.P.; Canouil, M.; Chee, M.L.; Chen, Y. I.; Cocca, M.; Connell, J.; de Silva, H.J.; de Vries, P. S.; Eiriksdottir, G.; Faul, J.D.; Fisher, V.; Forrester, T.; Fox, E.F.; Friedlander, Y.; Gao, H.; Gigante, B.; Giulianini, F.; Gu, C.C.; Gu, D.; Harris, T. B.; He, J.; Heikkinen, S.; Heng, C. K.; Hunt, S.; Ikram, M. A.; Irvin, M.R.; Kähönen, M.; Kavousi, M.; Khor, C.C.; Kilpeläinen, T.O.; Koh, W.P.; Komulainen, P.; Kraja, A.T.; Krieger, J.E.; Langefeld, C. D.; Li, Y.; Liang, J.; Liewald, D.C.M.; Liu, C.T.; Liu, J.; Lohman, K.K.; Mägi, R.; McKenzie, C.A.; Meitinger, T.; Metspalu, A.; Milaneschi, Y.; Milani, L.; Mook-Kanamori, D.O.; Nalls, M.A.; Nelson, C.P.; Norris, J. M.; O'Connell, J.; Ogunniyi, A.; Padmanabhan, S.; Palmer, N.D.; Pedersen, N. L.; Perls, T.; Peters, A.; Petersmann, A.; Peyser, P. A.; Polasek, O.; Porteous, D. J.; Raffel, L. J.; Rice, T. K.; Rotter, J.I.; Rudan, I.; Rueda-Ochoa, O.L.; Sabanayagam, C.; Salako, B. L.; Schreiner, P.J.; Shikany, J.M.; Sidney, S.S.; Sims, M.; Sitlani, C.M.; Smith, J. A.; Starr, J. M.; Strauch, K.; Swertz, M. A.; Teumer, A.; Tham, Y. C.; Uitterlinden, A.G.; Vaidya, D.; van der Ende, M.Y.; Waldenberger, M.; Wang, L.; Wang, Y. X.; Wei, W.B.; Weir, D.R.; Wen, W.; Yao, J.; Yu, B.; Yu, C.; Yuan, J. M.; Zhao, W.; Zonderman, A.B.; Becker, D.M.; Bowden, D.W.; Deary, I. J.; Dörr, M.; Esko, T.; Freedman, B. I.; Froguel, P.; Gasparini, P.; Gieger, C.; Jonas, J.B.; Kammerer, C.M.; Kato, N.; Lakka, T. A.; Leander, K.; Lehtimäki, T.; Lifelines Cohort Study; Magnusson, P. K. E.; Marques-Vidal, P.; Penninx, B. W. J. H.; Samani, N. J.; van der Harst, P.; Wagenknecht, L. E.; Wu, T.; Zheng, W.; Zhu, X.; Bouchard, C.; Cooper, R. S.; Correa, A.; Evans, M. K.; Gudnason, V.; Hayward, C.; Horta, B. L.; Kelly, T. N.; Kritchevsky, S. B.; Levy, D.; Palmas, W. R.; Pereira, A. C.; Province, M. M.; Psaty, B. M.; Ridker, P. M.; Rotimi, C. N.; Tai, E. S.; van Dam, R. M.; van Duijn, C. M.; Wong, T. Y.; Rice, K.; Gauderman, W. J.; Morrison, A. C.; North, K. E.; Kardia, S. L. R.; Caulfield, M. J.; Elliott, P.; Munroe, P. B.; Franks, P. W.; Rao, D. C.; Fornage, M.ABSTRACT:Educational attainment is widely used as a surrogate for socioeconomic status (SES). Low SES is a risk factor for hypertension and high blood pressure (BP). To identify novel BP loci, we performed multi-ancestry meta-analyses accounting for gene-educational attainment interactions using two variables, "Some College" (yes/no) and "Graduated College" (yes/no). Interactions were evaluated using both a 1 degree of freedom (DF) interaction term and a 2DF joint test of genetic and interaction effects. Analyses were performed for systolic BP, diastolic BP, mean arterial pressure, and pulse pressure. We pursued genome-wide interrogation in Stage 1 studies (N = 117 438) and follow-up on promising variants in Stage 2 studies (N = 293 787) in five ancestry groups. Through combined meta-analyses of Stages 1 and 2, we identified 84 known and 18 novel BP loci at genome-wide significance level (P < 5 × 10-8). Two novel loci were identified based on the 1DF test of interaction with educational attainment, while the remaining 16 loci were identified through the 2DF joint test of genetic and interaction effects. Ten novel loci were identified in individuals of African ancestry. Several novel loci show strong biological plausibility since they involve physiologic systems implicated in BP regulation. They include genes involved in the central nervous system-adrenal signaling axis (ZDHHC17, CADPS, PIK3C2G), vascular structure and function (GNB3, CDON), and renal function (HAS2 and HAS2-AS1, SLIT3). Collectively, these findings suggest a role of educational attainment or SES in further dissection of the genetic architecture of BP.Item A large-scale multi-ancestry genome-wide study accounting for smoking behavior identifies multiple significant loci for blood pressure(University of Chicago Press, 2018) Sung, Y.J.; Winkler, T.W.; de Las Fuentes, L.; Bentley, A.R.; Brown, M.R.; Kraja, A.T.; Schwander, K.; Ntalla, I.; Guo, X.; Franceschini, N.; Lu, Y.; Cheng, C.Y.; Sim, X.; Vojinovic, D.; Marten, J.; Musani, S.K.; Li, C.; Feitosa, M.F.; Kilpelainen, T.O.; Richard, M.A.; Noordam, R.; Aslibekyan, S.; Aschard, H.; Bartz, T.M.; Dorajoo, R.; Liu, Y.; Manning, A.K.; Rankinen, T.; Smith, A.V.; Tajuddin, S.M.; Tayo, B.O.; Warren, H.R.; Zhao, W.; Zhou, Y.; Matoba, N.; Sofer, T.; Alver, M.; Amini, M.; Boissel, M.; Chai, J.F.; Chen, X.; Divers, J.; Gandin, I.; Gao, C.; Giulianini, F.; Goel, A.; Harris, S.E.; Hatwig, F.P.; Horimoto, A.R.V.R.; Hsu, F.C.; Jackson, A.U.; Kahonen, M.; Kasturiratne, A.; Kuhnel, B.; Leander, K.; Lee, W.J.; Lin, K.H.; an Luan, J.; McKenzie, C.A.; Meian, H.; Nelson, C.P.; Rauramaa, R.; Schupf, N.; Scott, R.A.; Sheu, W.H.H.; Stancakova, A.; Takeuchi, F.; van der Most, P.J.; Varga, T.V.; Wang, H.; Wang, Y.; Ware, E.B.; Weiss, S.; Wen, W.; Yanek, L.R.; Zhang, W.; Zhao, J.H.; Afag, S.; Alfred, T.; Amin, N.; Arking, D.; Aung, T.; Barr, R.G.; Bielak, L.F.; Boerwincle, E.; Bottinger, E.P.; Braund, P.S.; Brody, J.A.; Broeckel, U.; Cabrera, C.P.; Cade, B.; Caizheng, Y.; Campbell, A.; Canouil, M.; Chakravarti, A.; CHARGE Neurology Working Group; Chauhan, G.; Christensen, K.; Cocca, M.; COGENT-Kidney Consortium; Collins, F.S.; Connel, J.M.; de Mutsert, R.; de Silva, H.J.; Debette, S.; Dorr, M.; Duan, Q.; Eaton, C.B.; Ehret, G.; Evangelou, E.; FAul, J.D.; Fisher, V.A.; Forouhi, N.G.; Franco, O.H.; Friedlander, Y.; Gao, H.; GIANT Consortium; Gigante, B.; Graff, M.; Gu, C.C.; Gu, D.; Gupta, P.; Hagenaars, S.P.; Harris, T.B.; He, J.; Heikkinen, S.; Heng, C.K.; Hirata, M.; Hofman., A.; Howard, B.V.; Hunt, S.; Irvin, M.R.; Jia, Y.; Joehanes, R.; Justice, A.E.; Katsuya, T.; Kaufman, J,; Kerrison, N.D.; Khor, C.C.; Koh, W.P.; Koistinen, H.A.; Komulainen, P.; Kooperberg, C.; Krieger, J.E.; Kubo, M.; Kuusisto, J.; Lanefeld, C.D.; Langenberg, C.; Launer, L.J.; Lehne, B.; Lewis, C.E.; Li, Y.; Lifelines Cohort Study; Lim, S.H.; Lin, S.; Liu, C.T.; Liu, J.; Liu, J.; Liu, K.; Liu, Y.; Loh, M.; Lohmann, K.K.; Long, J.; Louie, T.; Magi, R.; Mahajan, A.; Meitinger, T.; Metspalu, A.; Milani, L.; Momozawa, Y.; Morris, A.P.; Mosley, T.H.Jr.; Munson, P.; Murray, A.D.; Nalls, M.A.; Nasri, U.; Norris, J.M.; North, K.; Ogunniyi, A.; Padmanabhan, S.; Palmas, W.R.; Palmer, N.D.; Pankow, J.S.; Pedersen, N.L.; Peters, A.; Peyser, P.A.; Polasek, O.; Raitakari, O.T.; Renstrom, F.; Rice, T.K.; Ridker, P.M.; Robino, A.; Robinson, J.G.; Rose, L.M.; Rudan, I.; Salako, B.L.; Sandow, K.; Schmidt, C.O.; Schreiner, P.J.; Scott, W.R.; Seshadri, S.; Sever, P.; Sitlani, C.M.; Smith, J.A.; Snieder, H.; Starr, J.M.; Strauch, K.; Tang, H.; Taylor, K.D.; Teo, Y.Y.; Tham, Y.C.; Uitterlineden, A.G.; Waldenberger, M.; Wang, L.; Wang, Y.X.; Wei, W.B.; Williams, C.; Wilson, G.; Wojczynski, M.K.; Yao, J.; Yuan, J.M.; Zonderman, A.B.; Becker, D.M.; Boehnke, M.; Bowden, D.W.; Chambers, J.C.; Chen, Y.I.; de Faire, U.; Deary, I.J.; Esco, T.; Farrall, M.; Forrester, T.; Franks, P.W.; Freedman, B.I.; Froguel, P.; Gasparini, P.; Gieger, C.; Horta, B.L.; Hung, Y.J.; Jonas, J.B.; Kato, N.; Kooner, J.S.; Laakso, M.; Lehtimaki, T.; Liang, K.W.; Magnusson, P.K.E.; Newman, A.B.; Oldehinkel, A.J.; Pereira, A.C.; Redline, S.; Rettig, R.; Samani, N.J.; Scott, J.; Shu, X.O.; van der Harst, P.; Wagenknecht, L.E.; Wareham, N.J.; Watkins, H.; Weir, D.R.; Wickremasinghe, A.R.; Wu, T.; Zheng, W.; Kamatani, Y.; Laurie, C.C.; Bouchard, C.; Cooper, R.S.; Evans, M.K.; Gudnason, V.; Kardia, S.L.R.; Kritchevsky, S.B.; Levy, D.; O'Connell, J.R.; Psaty, B.M.; van Dam, R.M.; Sims, M.; Arnett, D.K.; Mook-Kanamori, D.O.; Kelly, T.N.; Fox, E.R.; Hayward, C.; Fornage, M.; Rotimi, C.N.; Province, M.A.; van Dujin, C.M.; Tai, E.S.; Wong, T.Y.; Loos, R.J.F.; Reiner, A.P.; Rotter, J.I.; Zhu, X.; Bierut, L.J.; Gauderman, W.J.; Caulfield, M.J.; Elliott, P.; Rice, K.; Munroe, P.B.; Morrison, A.C.; Cupples, L.A.; Rao., D.C.; Chasman, D.I.Genome-wide association analysis advanced understanding of blood pressure (BP), a major risk factor for vascular conditions such as coronary heart disease and stroke. Accounting for smoking behavior may help identify BP loci and extend our knowledge of its genetic architecture. We performed genome-wide association meta-analyses of systolic and diastolic BP incorporating gene-smoking interactions in 610,091 individuals. Stage 1 analysis examined ∼18.8 million SNPs and small insertion/deletion variants in 129,913 individuals from four ancestries (European, African, Asian, and Hispanic) with follow-up analysis of promising variants in 480,178 additional individuals from five ancestries. We identified 15 loci that were genome-wide significant (p < 5 × 10-8) in stage 1 and formally replicated in stage 2. A combined stage 1 and 2 meta-analysis identified 66 additional genome-wide significant loci (13, 35, and 18 loci in European, African, and trans-ancestry, respectively). A total of 56 known BP loci were also identified by our results (p < 5 × 10-8). Of the newly identified loci, ten showed significant interaction with smoking status, but none of them were replicated in stage 2. Several loci were identified in African ancestry, highlighting the importance of genetic studies in diverse populations. The identified loci show strong evidence for regulatory features and support shared pathophysiology with cardiometabolic and addiction traits. They also highlight a role in BP regulation for biological candidates such as modulators of vascular structure and function (CDKN1B, BCAR1-CFDP1, PXDN, EEA1), ciliopathies (SDCCAG8, RPGRIP1L), telomere maintenance (TNKS, PINX1, AKTIP), and central dopaminergic signaling (MSRA, EBF2).