Author: "Kamatani Y" / Publication Year Range: Last 3 years - Searchworks@Jio Institute Digital Library Search Results

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115 results on '"Kamatani Y"'

1. Understanding the genetic complexity of puberty timing across the allele frequency spectrum

Author: Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, Ong, KK, Kentistou, KA, Kaisinger, LR, Stankovic, S, Vaudel, M, Mendes de Oliveira, E, Messina, A, Walters, RG, Liu, X, Busch, AS, Helgason, H, Thompson, DJ, Santoni, F, Petricek, KM, Zouaghi, Y, Huang-Doran, I, Gudbjartsson, DF, Bratland, E, Lin, K, Gardner, EJ, Zhao, Y, Jia, RY, Terao, C, Riggan, MJ, Bolla, MK, Yazdanpanah, M, Yazdanpanah, N, Bradfield, JP, Broer, L, Campbell, A, Chasman, DI, Cousminer, DL, Franceschini, N, Franke, LH, Girotto, G, He, C, Järvelin, M-R, Joshi, PK, Kamatani, Y, Karlsson, R, Luan, J, Lunetta, KL, Mägi, R, Mangino, M, Medland, SE, Meisinger, C, Noordam, R, Nutile, T, Concas, MP, Polašek, O, Porcu, E, Ring, SM, Sala, C, Smith, AV, Tanaka, T, van der Most, PJ, Vitart, V, Wang, CA, Willemsen, G, Zygmunt, M, Ahearn, TU, Andrulis, IL, Anton-Culver, H, Antoniou, AC, Auer, PL, Barnes, CLK, Beckmann, MW, Berrington de Gonzalez, A, Bogdanova, NV, Bojesen, SE, Brenner, H, Buring, JE, Canzian, F, Chang-Claude, J, Couch, FJ, Cox, A, Crisponi, L, Czene, K, Daly, MB, Demerath, EW, Dennis, J, Devilee, P, De Vivo, I, Dörk, T, Dunning, AM, Dwek, M, Eriksson, JG, Fasching, PA, Fernandez-Rhodes, L, Ferreli, L, Fletcher, O, Gago-Dominguez, M, García-Closas, M, García-Sáenz, JA, González-Neira, A, Grallert, H, Guénel, P, Haiman, CA, Hall, P, Hamann, U, Hakonarson, H, Hart, RJ, Hickey, M, Hooning, MJ, Hoppe, R, Hopper, JL, Hottenga, J-J, Hu, FB, Huebner, H, Hunter, DJ, ABCTB Investigators, Jernström, H, John, EM, Karasik, D, Khusnutdinova, EK, Kristensen, VN, Lacey, JV, Lambrechts, D, Launer, LJ, Lind, PA, Lindblom, A, Magnusson, PKE, Mannermaa, A, McCarthy, MI, Meitinger, T, Menni, C, Michailidou, K, Millwood, IY, Milne, RL, Montgomery, GW, Nevanlinna, H, Nolte, IM, Nyholt, DR, Obi, N, O'Brien, KM, Offit, K, Oldehinkel, AJ, Ostrowski, SR, Palotie, A, Pedersen, OB, Peters, A, Pianigiani, G, Plaseska-Karanfilska, D, Pouta, A, Pozarickij, A, Radice, P, Rennert, G, Rosendaal, FR, Ruggiero, D, Saloustros, E, Sandler, DP, Schipf, S, Schmidt, CO, Schmidt, MK, Small, K, Spedicati, B, Stampfer, M, Stone, J, Tamimi, RM, Teras, LR, Tikkanen, E, Turman, C, Vachon, CM, Wang, Q, Winqvist, R, Wolk, A, Zemel, BS, Zheng, W, van Dijk, KW, Alizadeh, BZ, Bandinelli, S, Boerwinkle, E, Boomsma, DI, Ciullo, M, Chenevix-Trench, G, Cucca, F, Esko, T, Gieger, C, Grant, SFA, Gudnason, V, Hayward, C, Kolčić, I, Kraft, P, Lawlor, DA, Martin, NG, Nøhr, EA, Pedersen, NL, Pennell, CE, Ridker, PM, Robino, A, Snieder, H, Sovio, U, Spector, TD, Stöckl, D, Sudlow, C, Timpson, NJ, Toniolo, D, Uitterlinden, A, Ulivi, S, Völzke, H, Wareham, NJ, Widen, E, Wilson, JF, Lifelines Cohort Study, Danish Blood Donor Study, Ovarian Cancer Association Consortium, Breast Cancer Association Consortium, Biobank Japan Project, China Kadoorie Biobank Collaborative Group, Pharoah, PDP, Li, L, Easton, DF, Njølstad, PR, Sulem, P, Murabito, JM, Murray, A, Manousaki, D, Juul, A, Erikstrup, C, Stefansson, K, Horikoshi, M, Chen, Z, Farooqi, IS, Pitteloud, N, Johansson, S, Day, FR, Perry, JRB, and Ong, KK
Abstract: Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease.
Published: 2024

2. POS0354 IDENTIFICATION OF SOMATIC MUTATIONS IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS

Author: Iwasaki, T., primary, Ohmura, K., additional, Endo, C., additional, Shirakashi, M., additional, Hiwa, R., additional, Tsuji, H., additional, Kitagori, K., additional, Akizuki, S., additional, Nakashima, R., additional, Yoshifuji, H., additional, Morinobu, A., additional, Matsuda, F., additional, and Kamatani, Y., additional
Published: 2023
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3. Germ line DDX41 mutations define a unique subtype of myeloid neoplasms.

Author: Makishima, H., Saiki, R., Nannya, Y., Korotev, S., Gurnari, C., Takeda, J., Momozawa, Y., Best, S., Krishnamurthy, P., Yoshizato, T., Atsuta, Y., Shiozawa, Y., Iijima-Yamashita, Y., Yoshida, K., Shiraishi, Y., Nagata, Y., Kakiuchi, N., Onizuka, M., Chiba, K., Tanaka, H., Kon, A., Ochi, Y., Nakagawa, M.M., Okuda, R., Mori, T., Yoda, A., Itonaga, H., Miyazaki, Y., Sanada, M., Ishikawa, T., Chiba, S., Tsurumi, H., Kasahara, S., Müller-Tidow, C., Takaori-Kondo, A., Ohyashiki, K., Kiguchi, T., Matsuda, F., Jansen, J.H., Polprasert, C., Blombery, P., Kamatani, Y., Miyano, S., Malcovati, L., Haferlach, T, Kubo, M., Cazzola, M., Kulasekararaj, A.G., Godley, L.A., Maciejewski, J.P., Ogawa, S., Makishima, H., Saiki, R., Nannya, Y., Korotev, S., Gurnari, C., Takeda, J., Momozawa, Y., Best, S., Krishnamurthy, P., Yoshizato, T., Atsuta, Y., Shiozawa, Y., Iijima-Yamashita, Y., Yoshida, K., Shiraishi, Y., Nagata, Y., Kakiuchi, N., Onizuka, M., Chiba, K., Tanaka, H., Kon, A., Ochi, Y., Nakagawa, M.M., Okuda, R., Mori, T., Yoda, A., Itonaga, H., Miyazaki, Y., Sanada, M., Ishikawa, T., Chiba, S., Tsurumi, H., Kasahara, S., Müller-Tidow, C., Takaori-Kondo, A., Ohyashiki, K., Kiguchi, T., Matsuda, F., Jansen, J.H., Polprasert, C., Blombery, P., Kamatani, Y., Miyano, S., Malcovati, L., Haferlach, T, Kubo, M., Cazzola, M., Kulasekararaj, A.G., Godley, L.A., Maciejewski, J.P., and Ogawa, S.
Abstract: Item does not contain fulltext, Germ line DDX41 variants have been implicated in late-onset myeloid neoplasms (MNs). Despite an increasing number of publications, many important features of DDX41-mutated MNs remain to be elucidated. Here we performed a comprehensive characterization of DDX41-mutated MNs, enrolling a total of 346 patients with DDX41 pathogenic/likely-pathogenic (P/LP) germ line variants and/or somatic mutations from 9082 MN patients, together with 525 first-degree relatives of DDX41-mutated and wild-type (WT) patients. P/LP DDX41 germ line variants explained ∼80% of known germ line predisposition to MNs in adults. These risk variants were 10-fold more enriched in Japanese MN cases (n = 4461) compared with the general population of Japan (n = 20 238). This enrichment of DDX41 risk alleles was much more prominent in male than female (20.7 vs 5.0). P/LP DDX41 variants conferred a large risk of developing MNs, which was negligible until 40 years of age but rapidly increased to 49% by 90 years of age. Patients with myelodysplastic syndromes (MDS) along with a DDX41-mutation rapidly progressed to acute myeloid leukemia (AML), which was however, confined to those having truncating variants. Comutation patterns at diagnosis and at progression to AML were substantially different between DDX41-mutated and WT cases, in which none of the comutations affected clinical outcomes. Even TP53 mutations made no exceptions and their dismal effect, including multihit allelic status, on survival was almost completely mitigated by the presence of DDX41 mutations. Finally, outcomes were not affected by the conventional risk stratifications including the revised/molecular International Prognostic Scoring System. Our findings establish that MDS with DDX41-mutation defines a unique subtype of MNs that is distinct from other MNs.
Published: 2023

4. The genetic basis of endometriosis and comorbidity with other pain and inflammatory conditions

Author: Rahmioglu, N, Mortlock, S, Ghiasi, M, Moller, PL, Stefansdottir, L, Galarneau, G, Turman, C, Danning, R, Law, MH, Sapkota, Y, Christofidou, P, Skarp, S, Giri, A, Banasik, K, Krassowski, M, Lepamets, M, Marciniak, B, Noukas, M, Perro, D, Sliz, E, Sobalska-Kwapis, M, Thorleifsson, G, Topbas-Selcuki, NF, Vitonis, A, Westergaard, D, Arnadottir, R, Burgdorf, KS, Campbell, A, Cheuk, CSK, Clementi, C, Cook, J, De Vivo, I, DiVasta, A, Dorien, O, Donoghue, JF, Edwards, T, Fontanillas, P, Fung, JN, Geirsson, RT, Girling, JE, Harkki, P, Harris, HR, Healey, M, Heikinheimo, O, Holdsworth-Carson, S, Hostettler, IC, Houlden, H, Houshdaran, S, Irwin, JC, Jarvelin, M-R, Kamatani, Y, Kennedy, SH, Kepka, E, Kettunen, J, Kubo, M, Kulig, B, Kurra, V, Laivuori, H, Laufer, MR, Lindgren, CM, MacGregor, S, Mangino, M, Martin, NG, Matalliotaki, C, Matalliotakis, M, Murray, AD, Ndungu, A, Nezhat, C, Olsen, CM, Opoku-Anane, J, Padmanabhan, S, Paranjpe, M, Peters, M, Polak, G, Porteous, DJ, Rabban, J, Rexrode, KM, Romanowicz, H, Saare, M, Saavalainen, L, Schork, AJ, Sen, S, Shafrir, AL, Siewierska-Gorska, A, Slomka, M, Smith, BH, Smolarz, B, Szaflik, T, Szyllo, K, Takahashi, A, Terry, KL, Tomassetti, C, Treloar, SA, Vanhie, A, Vincent, K, Vo, KC, Werring, DJ, Zeggini, E, Zervou, M, Stefansson, K, Nyegaard, M, Uimari, O, Yurttas-Beim, P, Tung, JY, Adachi, S, Buring, JE, Ridker, PM, D'Hooghe, T, Goulielmos, GN, Hapangama, DK, Hayward, C, Horne, AW, Low, S-K, Martikainen, H, Chasman, D, Rogers, PAW, Saunders, PT, Sirota, M, Spector, T, Strapagiel, D, Whiteman, DC, Giudice, LC, Velez-Edwards, DR, Kraft, P, Salumets, A, Nyholt, DR, Magi, R, Becker, CM, Steinthorsdottir, V, Missmer, SA, Montgomery, GW, Morris, AP, Zondervan, KT, Rahmioglu, N, Mortlock, S, Ghiasi, M, Moller, PL, Stefansdottir, L, Galarneau, G, Turman, C, Danning, R, Law, MH, Sapkota, Y, Christofidou, P, Skarp, S, Giri, A, Banasik, K, Krassowski, M, Lepamets, M, Marciniak, B, Noukas, M, Perro, D, Sliz, E, Sobalska-Kwapis, M, Thorleifsson, G, Topbas-Selcuki, NF, Vitonis, A, Westergaard, D, Arnadottir, R, Burgdorf, KS, Campbell, A, Cheuk, CSK, Clementi, C, Cook, J, De Vivo, I, DiVasta, A, Dorien, O, Donoghue, JF, Edwards, T, Fontanillas, P, Fung, JN, Geirsson, RT, Girling, JE, Harkki, P, Harris, HR, Healey, M, Heikinheimo, O, Holdsworth-Carson, S, Hostettler, IC, Houlden, H, Houshdaran, S, Irwin, JC, Jarvelin, M-R, Kamatani, Y, Kennedy, SH, Kepka, E, Kettunen, J, Kubo, M, Kulig, B, Kurra, V, Laivuori, H, Laufer, MR, Lindgren, CM, MacGregor, S, Mangino, M, Martin, NG, Matalliotaki, C, Matalliotakis, M, Murray, AD, Ndungu, A, Nezhat, C, Olsen, CM, Opoku-Anane, J, Padmanabhan, S, Paranjpe, M, Peters, M, Polak, G, Porteous, DJ, Rabban, J, Rexrode, KM, Romanowicz, H, Saare, M, Saavalainen, L, Schork, AJ, Sen, S, Shafrir, AL, Siewierska-Gorska, A, Slomka, M, Smith, BH, Smolarz, B, Szaflik, T, Szyllo, K, Takahashi, A, Terry, KL, Tomassetti, C, Treloar, SA, Vanhie, A, Vincent, K, Vo, KC, Werring, DJ, Zeggini, E, Zervou, M, Stefansson, K, Nyegaard, M, Uimari, O, Yurttas-Beim, P, Tung, JY, Adachi, S, Buring, JE, Ridker, PM, D'Hooghe, T, Goulielmos, GN, Hapangama, DK, Hayward, C, Horne, AW, Low, S-K, Martikainen, H, Chasman, D, Rogers, PAW, Saunders, PT, Sirota, M, Spector, T, Strapagiel, D, Whiteman, DC, Giudice, LC, Velez-Edwards, DR, Kraft, P, Salumets, A, Nyholt, DR, Magi, R, Becker, CM, Steinthorsdottir, V, Missmer, SA, Montgomery, GW, Morris, AP, and Zondervan, KT
Abstract: Endometriosis is a common condition associated with debilitating pelvic pain and infertility. A genome-wide association study meta-analysis, including 60,674 cases and 701,926 controls of European and East Asian descent, identified 42 genome-wide significant loci comprising 49 distinct association signals. Effect sizes were largest for stage 3/4 disease, driven by ovarian endometriosis. Identified signals explained up to 5.01% of disease variance and regulated expression or methylation of genes in endometrium and blood, many of which were associated with pain perception/maintenance (SRP14/BMF, GDAP1, MLLT10, BSN and NGF). We observed significant genetic correlations between endometriosis and 11 pain conditions, including migraine, back and multisite chronic pain (MCP), as well as inflammatory conditions, including asthma and osteoarthritis. Multitrait genetic analyses identified substantial sharing of variants associated with endometriosis and MCP/migraine. Targeted investigations of genetically regulated mechanisms shared between endometriosis and other pain conditions are needed to aid the development of new treatments and facilitate early symptomatic intervention.
Published: 2023

5. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

Author: Wang, A, Shen, J, Rodriguez, AA, Saunders, EJ, Chen, F, Janivara, R, Darst, BF, Sheng, X, Xu, Y, Chou, AJ, Benlloch, S, Dadaev, T, Brook, MN, Plym, A, Sahimi, A, Hoffman, TJ, Takahashi, A, Matsuda, K, Momozawa, Y, Fujita, M, Laisk, T, Figuerêdo, J, Muir, K, Ito, S, Liu, X, Biobank Japan Project, Uchio, Y, Kubo, M, Kamatani, Y, Lophatananon, A, Wan, P, Andrews, C, Lori, A, Choudhury, PP, Schleutker, J, Tammela, TLJ, Sipeky, C, Auvinen, A, Giles, GG, Southey, MC, MacInnis, RJ, Cybulski, C, Wokolorczyk, D, Lubinski, J, Rentsch, CT, Cho, K, Mcmahon, BH, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Nordestgaard, BG, Nielsen, SF, Weischer, M, Bojesen, SE, Røder, A, Stroomberg, HV, Batra, J, Chambers, S, Horvath, L, Clements, JA, Tilly, W, Risbridger, GP, Gronberg, H, Aly, M, Szulkin, R, Eklund, M, Nordstrom, T, Pashayan, N, Dunning, AM, Ghoussaini, M, Travis, RC, Key, TJ, Riboli, E, Park, JY, Sellers, TA, Lin, H-Y, Albanes, D, Weinstein, S, Cook, MB, Mucci, LA, Giovannucci, E, Lindstrom, S, Kraft, P, Hunter, DJ, Penney, KL, Turman, C, Tangen, CM, Goodman, PJ, Thompson, IM, Hamilton, RJ, Fleshner, NE, Finelli, A, Parent, M-É, Stanford, JL, Ostrander, EA, Koutros, S, Beane Freeman, LE, Stampfer, M, Wolk, A, Håkansson, N, Andriole, GL, Hoover, RN, Machiela, MJ, Sørensen, KD, Borre, M, Blot, WJ, Zheng, W, Yeboah, ED, Mensah, JE, Lu, Y-J, Zhang, H-W, Feng, N, Mao, X, Wu, Y, Zhao, S-C, Sun, Z, Thibodeau, SN, McDonnell, SK, Schaid, DJ, West, CML, Barnett, G, Maier, C, Schnoeller, T, Luedeke, M, Kibel, AS, Drake, BF, Cussenot, O, Cancel-Tassin, G, Menegaux, F, Truong, T, Koudou, YA, John, EM, Grindedal, EM, Maehle, L, Khaw, K-T, Ingles, SA, Stern, MC, Vega, A, Gómez-Caamaño, A, Fachal, L, Rosenstein, BS, Kerns, SL, Ostrer, H, Teixeira, MR, Paulo, P, Brandão, A, Watya, S, Lubwama, A, Bensen, JT, Butler, EN, Mohler, JL, Taylor, JA, Kogevinas, M, Dierssen-Sotos, T, Castaño-Vinyals, G, Cannon-Albright, L, Teerlink, CC, Huff, CD, Pilie, P, Yu, Y, Bohlender, RJ, Gu, J, Strom, SS, Multigner, L, Blanchet, P, Brureau, L, Kaneva, R, Slavov, C, Mitev, V, Leach, RJ, Brenner, H, Chen, X, Holleczek, B, Schöttker, B, Klein, EA, Hsing, AW, Kittles, RA, Murphy, AB, Logothetis, CJ, Kim, J, Neuhausen, SL, Steele, L, Ding, YC, Isaacs, WB, Nemesure, B, Hennis, AJM, Carpten, J, Pandha, H, Michael, A, De Ruyck, K, De Meerleer, G, Ost, P, Xu, J, Razack, A, Lim, J, Teo, S-H, Newcomb, LF, Lin, DW, Fowke, JH, Neslund-Dudas, CM, Rybicki, BA, Gamulin, M, Lessel, D, Kulis, T, Usmani, N, Abraham, A, Singhal, S, Parliament, M, Claessens, F, Joniau, S, Van den Broeck, T, Gago-Dominguez, M, Castelao, JE, Martinez, ME, Larkin, S, Townsend, PA, Aukim-Hastie, C, Bush, WS, Aldrich, MC, Crawford, DC, Srivastava, S, Cullen, J, Petrovics, G, Casey, G, Wang, Y, Tettey, Y, Lachance, J, Tang, W, Biritwum, RB, Adjei, AA, Tay, E, Truelove, A, Niwa, S, Yamoah, K, Govindasami, K, Chokkalingam, AP, Keaton, JM, Hellwege, JN, Clark, PE, Jalloh, M, Gueye, SM, Niang, L, Ogunbiyi, O, Shittu, O, Amodu, O, Adebiyi, AO, Aisuodionoe-Shadrach, OI, Ajibola, HO, Jamda, MA, Oluwole, OP, Nwegbu, M, Adusei, B, Mante, S, Darkwa-Abrahams, A, Diop, H, Gundell, SM, Roobol, MJ, Jenster, G, van Schaik, RHN, Hu, JJ, Sanderson, M, Kachuri, L, Varma, R, McKean-Cowdin, R, Torres, M, Preuss, MH, Loos, RJF, Zawistowski, M, Zöllner, S, Lu, Z, Van Den Eeden, SK, Easton, DF, Ambs, S, Edwards, TL, Mägi, R, Rebbeck, TR, Fritsche, L, Chanock, SJ, Berndt, SI, Wiklund, F, Nakagawa, H, Witte, JS, Gaziano, JM, Justice, AC, Mancuso, N, Terao, C, Eeles, RA, Kote-Jarai, Z, Madduri, RK, Conti, DV, Haiman, CA, Wang, A, Shen, J, Rodriguez, AA, Saunders, EJ, Chen, F, Janivara, R, Darst, BF, Sheng, X, Xu, Y, Chou, AJ, Benlloch, S, Dadaev, T, Brook, MN, Plym, A, Sahimi, A, Hoffman, TJ, Takahashi, A, Matsuda, K, Momozawa, Y, Fujita, M, Laisk, T, Figuerêdo, J, Muir, K, Ito, S, Liu, X, Biobank Japan Project, Uchio, Y, Kubo, M, Kamatani, Y, Lophatananon, A, Wan, P, Andrews, C, Lori, A, Choudhury, PP, Schleutker, J, Tammela, TLJ, Sipeky, C, Auvinen, A, Giles, GG, Southey, MC, MacInnis, RJ, Cybulski, C, Wokolorczyk, D, Lubinski, J, Rentsch, CT, Cho, K, Mcmahon, BH, Neal, DE, Donovan, JL, Hamdy, FC, Martin, RM, Nordestgaard, BG, Nielsen, SF, Weischer, M, Bojesen, SE, Røder, A, Stroomberg, HV, Batra, J, Chambers, S, Horvath, L, Clements, JA, Tilly, W, Risbridger, GP, Gronberg, H, Aly, M, Szulkin, R, Eklund, M, Nordstrom, T, Pashayan, N, Dunning, AM, Ghoussaini, M, Travis, RC, Key, TJ, Riboli, E, Park, JY, Sellers, TA, Lin, H-Y, Albanes, D, Weinstein, S, Cook, MB, Mucci, LA, Giovannucci, E, Lindstrom, S, Kraft, P, Hunter, DJ, Penney, KL, Turman, C, Tangen, CM, Goodman, PJ, Thompson, IM, Hamilton, RJ, Fleshner, NE, Finelli, A, Parent, M-É, Stanford, JL, Ostrander, EA, Koutros, S, Beane Freeman, LE, Stampfer, M, Wolk, A, Håkansson, N, Andriole, GL, Hoover, RN, Machiela, MJ, Sørensen, KD, Borre, M, Blot, WJ, Zheng, W, Yeboah, ED, Mensah, JE, Lu, Y-J, Zhang, H-W, Feng, N, Mao, X, Wu, Y, Zhao, S-C, Sun, Z, Thibodeau, SN, McDonnell, SK, Schaid, DJ, West, CML, Barnett, G, Maier, C, Schnoeller, T, Luedeke, M, Kibel, AS, Drake, BF, Cussenot, O, Cancel-Tassin, G, Menegaux, F, Truong, T, Koudou, YA, John, EM, Grindedal, EM, Maehle, L, Khaw, K-T, Ingles, SA, Stern, MC, Vega, A, Gómez-Caamaño, A, Fachal, L, Rosenstein, BS, Kerns, SL, Ostrer, H, Teixeira, MR, Paulo, P, Brandão, A, Watya, S, Lubwama, A, Bensen, JT, Butler, EN, Mohler, JL, Taylor, JA, Kogevinas, M, Dierssen-Sotos, T, Castaño-Vinyals, G, Cannon-Albright, L, Teerlink, CC, Huff, CD, Pilie, P, Yu, Y, Bohlender, RJ, Gu, J, Strom, SS, Multigner, L, Blanchet, P, Brureau, L, Kaneva, R, Slavov, C, Mitev, V, Leach, RJ, Brenner, H, Chen, X, Holleczek, B, Schöttker, B, Klein, EA, Hsing, AW, Kittles, RA, Murphy, AB, Logothetis, CJ, Kim, J, Neuhausen, SL, Steele, L, Ding, YC, Isaacs, WB, Nemesure, B, Hennis, AJM, Carpten, J, Pandha, H, Michael, A, De Ruyck, K, De Meerleer, G, Ost, P, Xu, J, Razack, A, Lim, J, Teo, S-H, Newcomb, LF, Lin, DW, Fowke, JH, Neslund-Dudas, CM, Rybicki, BA, Gamulin, M, Lessel, D, Kulis, T, Usmani, N, Abraham, A, Singhal, S, Parliament, M, Claessens, F, Joniau, S, Van den Broeck, T, Gago-Dominguez, M, Castelao, JE, Martinez, ME, Larkin, S, Townsend, PA, Aukim-Hastie, C, Bush, WS, Aldrich, MC, Crawford, DC, Srivastava, S, Cullen, J, Petrovics, G, Casey, G, Wang, Y, Tettey, Y, Lachance, J, Tang, W, Biritwum, RB, Adjei, AA, Tay, E, Truelove, A, Niwa, S, Yamoah, K, Govindasami, K, Chokkalingam, AP, Keaton, JM, Hellwege, JN, Clark, PE, Jalloh, M, Gueye, SM, Niang, L, Ogunbiyi, O, Shittu, O, Amodu, O, Adebiyi, AO, Aisuodionoe-Shadrach, OI, Ajibola, HO, Jamda, MA, Oluwole, OP, Nwegbu, M, Adusei, B, Mante, S, Darkwa-Abrahams, A, Diop, H, Gundell, SM, Roobol, MJ, Jenster, G, van Schaik, RHN, Hu, JJ, Sanderson, M, Kachuri, L, Varma, R, McKean-Cowdin, R, Torres, M, Preuss, MH, Loos, RJF, Zawistowski, M, Zöllner, S, Lu, Z, Van Den Eeden, SK, Easton, DF, Ambs, S, Edwards, TL, Mägi, R, Rebbeck, TR, Fritsche, L, Chanock, SJ, Berndt, SI, Wiklund, F, Nakagawa, H, Witte, JS, Gaziano, JM, Justice, AC, Mancuso, N, Terao, C, Eeles, RA, Kote-Jarai, Z, Madduri, RK, Conti, DV, and Haiman, CA
Abstract: The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
Published: 2023

6. Contribution of Common Genetic Variants to Risk of Early Onset Ischemic Stroke

Author: Jaworek, T, Xu, H, Gaynor, BJ, Cole, JW, Rannikmae, K, Stanne, TM, Tomppo, L, Abedi, V, Amouyel, P, Armstrong, ND, Attia, J, Bell, S, Benavente, OR, Boncoraglio, GB, Butterworth, A, Cervical Artery Dissections and Ischemic Stroke Patients (CADSIP) Consortium, Carcel-Marquez, J, Chen, Z, Chong, M, Cruchaga, C, Cushman, M, Danesh, J, Debette, S, Duggan, DJ, Durda, JP, Engstrom, G, Enzinger, C, Faul, JD, Fecteau, NS, Fernandez-Cadenas, I, Gieger, C, Giese, A-K, Grewal, RP, Grittner, U, Havulinna, AS, Heitsch, L, Hochberg, MC, Holliday, E, Hu, J, Ilinca, A, INVENT Consortium, Irvin, MR, Jackson, RD, Jacob, MA, Janssen, RR, Jimenez-Conde, J, Johnson, JA, Kamatani, Y, Kardia, SL, Koido, M, Kubo, M, Lange, L, Lee, J-M, Lemmens, R, Levi, CR, Li, J, Li, L, Lin, K, Lopez, H, Luke, S, Maguire, J, McArdle, PF, McDonough, CW, Meschia, JF, Metso, T, Muller-Nurasyid, M, O'Connor, TD, O'Donnell, M, Peddareddygari, LR, Pera, J, Perry, JA, Peters, A, Putaala, J, Ray, D, Rexrode, K, Ribases, M, Rosand, J, Rothwell, PM, Rundek, T, Ryan, KA, Sacco, RL, Salomaa, V, Sanchez-Mora, C, Schmidt, R, Sharma, P, Slowik, A, Smith, JA, Smith, NL, Wassertheil-Smoller, S, Soederholm, M, Stine, OC, Strbian, D, Sudlow, CL, Tatlisumak, T, Terao, C, Thijs, V, Torres-Aguila, NP, Tregouet, D-A, Tuladhar, AM, Veldink, JH, Walters, RG, Weir, DR, Woo, D, Worrall, BB, Hong, CC, Ross, O, Zand, R, Leeuw, F-ED, Lindgren, AG, Pare, G, Anderson, CD, Markus, HS, Jern, C, Malik, R, Dichgans, M, Mitchell, BD, Kittner, SJ, and Early Onset Stroke Genetics Consortium of the International Stroke Genetics Consortium (ISGC)
Subjects: Neurology & Neurosurgery, 1103 Clinical Sciences, 1109 Neurosciences, 1702 Cognitive Sciences
Abstract: BACKGROUND AND OBJECTIVES: Current genome-wide association studies of ischemic stroke have focused primarily on late onset disease. As a complement to these studies, we sought to identifythe contribution of common genetic variants to risk of early onset ischemic stroke. METHODS: We performed a meta-analysis of genome-wide association studies of early onset stroke (EOS), ages 18-59, using individual level data or summary statistics in 16,730 cases and 599,237 non-stroke controls obtained across 48 different studies. We further compared effect sizes at associated loci between EOS and late onset stroke (LOS) and compared polygenic risk scores for venous thromboembolism between EOS and LOS. RESULTS: We observed genome-wide significant associations of EOS with two variants in ABO, a known stroke locus. These variants tag blood subgroups O1 and A1, and the effect sizes of both variants were significantly larger in EOS compared to LOS. The odds ratio (OR) for rs529565, tagging O1, 0.88 (95% CI: 0.85-0.91) in EOS vs 0.96 (95% CI: 0.92-1.00) in LOS, and the OR for rs635634, tagging A1, was 1.16 (1.11-1.21) for EOS vs 1.05 (0.99-1.11) in LOS; p-values for interaction = 0.001 and 0.005, respectively. Using polygenic risk scores, we observed that greater genetic risk for venous thromboembolism, another prothrombotic condition, was more strongly associated with EOS compared to LOS (p=0.008). DISCUSSION: The ABO locus, genetically predicted blood group A, and higher genetic propensity for venous thrombosis are more strongly associated with EOS than with LOS, supporting a stronger role of prothrombotic factors in EOS.
Published: 2022

7. Genome-Wide Meta-analysis Identifies Genetic Variants Associated With Glycemic Response to Sulfonylureas. Diabetes Care 2021;44:2673-2682

Author: Dawed, A.Y., Yee, S.W., Zhou, K.X., Leeuwen, N. van, Zhang, Y.F., Siddiqui, M.K., Etheridge, A., Innocenti, F., Xu, F., Li, J.H., Beulens, J.W., Heijden, A.A. van der, Slieker, R.C., Chang, Y.C., Mercader, J.M., Kaur, V., Witte, J.S., Lee, M.T.M., Kamatani, Y., Momozawa, Y., Kubo, M., Palmer, C.N.A., Florez, J.C., Hedderson, M.M., Hart, L.M. 't, Giacomini, K.M., Pearson, E.R., and MetGen Plus DIRECT Consortium
Published: 2022

8. A polygenic risk score improves risk stratification of coronary artery disease: a large-scale prospective Chinese cohort study.

Author: Lu, X, Liu, Z, Cui, Q, Liu, F, Li, J, Niu, X, Shen, C, Hu, D, Huang, K, Chen, J, Xing, X, Zhao, Y, Lu, F, Liu, X, Cao, J, Chen, S, Ma, H, Yu, L, Wu, X, Li, Y, Zhang, H, Mo, X, Zhao, L, Huang, J, Wang, L, Wen, W, Shu, X-O, Takeuchi, F, Koh, W-P, Tai, ES, Cheng, C-Y, Wong, TY, Chang, X, Chan, MY-Y, Gao, W, Zheng, H, Chen, K, He, J, Tang, CS-M, Lam, KSL, Tse, H-F, Cheung, CYY, Takahashi, A, Kubo, M, Kato, N, Terao, C, Kamatani, Y, Sham, PC, Heng, C-K, Hu, Z, Chen, YE, Wu, T, Shen, H, Willer, CJ, Gu, D, Lu, X, Liu, Z, Cui, Q, Liu, F, Li, J, Niu, X, Shen, C, Hu, D, Huang, K, Chen, J, Xing, X, Zhao, Y, Lu, F, Liu, X, Cao, J, Chen, S, Ma, H, Yu, L, Wu, X, Li, Y, Zhang, H, Mo, X, Zhao, L, Huang, J, Wang, L, Wen, W, Shu, X-O, Takeuchi, F, Koh, W-P, Tai, ES, Cheng, C-Y, Wong, TY, Chang, X, Chan, MY-Y, Gao, W, Zheng, H, Chen, K, He, J, Tang, CS-M, Lam, KSL, Tse, H-F, Cheung, CYY, Takahashi, A, Kubo, M, Kato, N, Terao, C, Kamatani, Y, Sham, PC, Heng, C-K, Hu, Z, Chen, YE, Wu, T, Shen, H, Willer, CJ, and Gu, D
Abstract: AIMS: To construct a polygenic risk score (PRS) for coronary artery disease (CAD) and comprehensively evaluate its potential in clinical utility for primary prevention in Chinese populations. METHODS AND RESULTS: Using meta-analytic approach and large genome-wide association results for CAD and CAD-related traits in East Asians, a PRS comprising 540 genetic variants was developed in a training set of 2800 patients with CAD and 2055 controls, and was further assessed for risk stratification for CAD integrating with the guideline-recommended clinical risk score in large prospective cohorts comprising 41 271 individuals. During a mean follow-up of 13.0 years, 1303 incident CAD cases were identified. Individuals with high PRS (the highest 20%) had about three-fold higher risk of CAD than the lowest 20% (hazard ratio 2.91, 95% confidence interval 2.43-3.49), with the lifetime risk of 15.9 and 5.8%, respectively. The addition of PRS to the clinical risk score yielded a modest yet significant improvement in C-statistic (1%) and net reclassification improvement (3.5%). We observed significant gradients in both 10-year and lifetime risk of CAD according to the PRS within each clinical risk strata. Particularly, when integrating high PRS, intermediate clinical risk individuals with uncertain clinical decision for intervention would reach the risk levels (10-year of 4.6 vs. 4.8%, lifetime of 17.9 vs. 16.6%) of high clinical risk individuals with intermediate (20-80%) PRS. CONCLUSION: The PRS could stratify individuals into different trajectories of CAD risk, and further refine risk stratification for CAD within each clinical risk strata, demonstrating a great potential to identify high-risk individuals for targeted intervention in clinical utility.
Published: 2022

9. Stroke genetics informs drug discovery and risk prediction across ancestries

Author: Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Carty, CL, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, van Hylckama Vlieg, A, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianini, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Irvin, MR, de Leeuw, F-E, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Anderson, CD, Lopez, OL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Lemmens, R, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Muller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, HI, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Lee, J-M, Cheng, Y-C, Meschia, JF, Chen, WM, Sale, MM, Zonderman, AB, Evans, MK, Wilson, JG, Correa, A, Traylor, M, Lewis, CM, Carty, CL, Reiner, A, Haessler, J, Langefeld, CD, Gottesman, RF, Yaffe, K, Liu, YM, Kooperberg, C, Lange, LA, Furie, KL, Arnett, DK, Benavente, OR, Grewal, RP, Peddareddygari, LR, Hveem, K, Lindstrom, S, Wang, L, Smith, EN, Gordon, W, van Hylckama Vlieg, A, de Andrade, M, Brody, JA, Pattee, JW, Brumpton, BM, Suchon, P, Chen, M-H, Frazer, KA, Turman, C, Germain, M, MacDonald, J, Braekkan, SK, Armasu, SM, Pankratz, N, Jackson, RD, Nielsen, JB, Giulianini, F, Puurunen, MK, Ibrahim, M, Heckbert, SR, Bammler, TK, McCauley, BM, Taylor, KD, Pankow, JS, Reiner, AP, Gabrielsen, ME, Deleuze, J-F, O'Donnell, CJ, Kim, J, McKnight, B, Kraft, P, Hansen, J-B, Rosendaal, FR, Heit, JA, Tang, W, Morange, P-E, Johnson, AD, Kabrhel, C, van Dijk, EJ, Koudstaal, PJ, Luijckx, G-J, Nederkoorn, PJ, van Oostenbrugge, RJ, Visser, MC, Wermer, MJH, Kappelle, LJ, Esko, T, Metspalu, A, Magi, R, Nelis, M, Irvin, MR, de Leeuw, F-E, Levi, CR, Maguire, J, Jimenez-Conde, J, Sharma, P, Sudlow, CLM, Rannikmae, K, Schmidt, R, Slowik, A, Pera, J, Thijs, VNS, Lindgren, AG, Ilinca, A, Melander, O, Engstrom, G, Rexrode, KM, Rothwell, PM, Stanne, TM, Johnson, JA, Danesh, J, Butterworth, AS, Heitsch, L, Boncoraglio, GB, Kubo, M, Pezzini, A, Rolfs, A, Giese, A-K, Weir, D, Ross, OA, Lemmons, R, Soderholm, M, Cushman, M, Jood, K, McDonough, CW, Bell, S, Linkohr, B, Lee, T-H, Putaala, J, Anderson, CD, Lopez, OL, Jian, X, Schminke, U, Cullell, N, Delgado, P, Ibanez, L, Krupinski, J, Lioutas, V, Matsuda, K, Montaner, J, Muino, E, Roquer, J, Sarnowski, C, Sattar, N, Sibolt, G, Teumer, A, Rutten-Jacobs, L, Kanai, M, Gretarsdottir, S, Rost, NS, Yusuf, S, Almgren, P, Ay, H, Bevan, S, Brown, RD, Carrera, C, Buring, JE, Chen, W-M, Cotlarciuc, I, de Bakker, PIW, DeStefano, AL, den Hoed, M, Duan, Q, Engelter, ST, Falcone, GJ, Gustafsson, S, Hassan, A, Holliday, EG, Howard, G, Hsu, F-C, Ingelsson, E, Harris, TB, Kissela, BM, Kleindorfer, DO, Langenberg, C, Lemmens, R, Leys, D, Lin, W-Y, Lorentzen, E, Magnusson, PK, McArdle, PF, Pulit, SL, Rice, K, Sakaue, S, Sapkota, BR, Tanislav, C, Thorleifsson, G, Thorsteinsdottir, U, Tzourio, C, van Duijn, CM, Walters, M, Wareham, NJ, Amin, N, Aparicio, HJ, Attia, J, Beiser, AS, Berr, C, Bustamante, M, Caso, V, Choi, SH, Chowhan, A, Dartigues, J-F, Delavaran, H, Dorr, M, Ford, I, Gurpreet, WS, Hamsten, A, Hozawa, A, Ingelsson, M, Iwasaki, M, Kaffashian, S, Kalra, L, Kjartansson, O, Kloss, M, Labovitz, DL, Laurie, CC, Lind, L, Lindgren, CM, Makoto, H, Minegishi, N, Morris, AP, Muller-Nurasyid, M, Norrving, B, Ogishima, S, Parati, EA, Pedersen, NL, Perola, M, Jousilahti, P, Pileggi, S, Rabionet, R, Riba-Llena, I, Ribases, M, Romero, JR, Rudd, AG, Sarin, A-P, Sarju, R, Satoh, M, Sawada, N, Sigurdsson, A, Smith, A, Stine, OC, Stott, DJ, Strauch, K, Takai, T, Tanaka, H, Touze, E, Tsugane, S, Uitterlinden, AG, Valdimarsson, EM, van der Lee, SJ, Wakai, K, Williams, SR, Wolfe, CDA, Wong, Q, Yamaji, T, Sanghera, DK, Stefansson, K, Martinez-Majander, N, Sobue, K, Soriano-Tarraga, C, Volzke, H, Akpa, O, Sarfo, FS, Akpalu, A, Obiako, R, Wahab, K, Osaigbovo, G, Owolabi, L, Komolafe, M, Jenkins, C, Arulogun, O, Ogbole, G, Adeoye, AM, Akinyemi, J, Agunloye, A, Fakunle, AG, Uvere, E, Olalere, A, Adebajo, OJ, Chen, J, Clarke, R, Collins, R, Guo, Y, Wang, C, Lv, J, Peto, R, Chen, Y, Fairhurst-Hunter, Z, Hill, M, Pozarickij, A, Schmidt, D, Stevens, B, Turnbull, I, Yu, C, Nagai, A, Murakami, Y, Shiroma, EJ, Sigurdsson, S, Ghanbari, M, Boerwinkle, E, Fongang, B, Wang, R, Ikram, MK, Volker, U, de Laat, KF, van Norden, AGW, de Kort, PL, Vermeer, SE, Brouwers, PJAM, Gons, RAR, den Heijer, T, van Dijk, GW, van Rooij, FGW, Aamodt, AH, Skogholt, AH, Willer, CJ, Heuch, I, Hagen, K, Fritsche, LG, Pedersen, LM, Ellekjaer, H, Zhou, W, Martinsen, AE, Kristoffersen, ES, Thomas, LF, Kleinschnitz, C, Frantz, S, Ungethum, K, Gallego-Fabrega, C, Lledos, M, Llucia-Carol, L, Sobrino, T, Campos, F, Castillo, J, Freijo, M, Arenillas, JF, Obach, V, Alvarez-Sabin, J, Molina, CA, Ribo, M, Munoz-Narbona, L, Lopez-Cancio, E, Millan, M, Diaz-Navarro, R, Vives-Bauza, C, Serrano-Heras, G, Segura, T, Dhar, R, Delgado-Mederos, R, Prats-Sanchez, L, Camps-Renom, P, Blay, N, Sumoy, L, Marti-Fabregas, J, Schnohr, P, Jensen, GB, Benn, M, Afzal, S, Kamstrup, PR, van Setten, J, van der Laan, SW, Vonk, JMJ, Kim, B-J, Curtze, S, Tiainen, M, Kinnunen, J, Menon, V, Sung, YJ, Saillour-Glenisson, F, Gravel, S, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, and Debette, S
Abstract: Previous genome-wide association studies (GWASs) of stroke - the second leading cause of death worldwide - were conducted predominantly in populations of European ancestry1,2. 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 analysis3, 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 approach4, 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 ancestry5. 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.
Published: 2022

10. A saturated map of common genetic variants associated with human height

Author: Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, Hirschhorn, JN, Yengo, L, Vedantam, S, Marouli, E, Sidorenko, J, Bartell, E, Sakaue, S, Graff, M, Eliasen, AU, Jiang, Y, Raghavan, S, Miao, J, Arias, JD, Graham, SE, Mukamel, RE, Spracklen, CN, Yin, X, Chen, S-H, Ferreira, T, Highland, HH, Ji, Y, Karaderi, T, Lin, K, Lull, K, Malden, DE, Medina-Gomez, C, Machado, M, Moore, A, Rueger, S, Sim, X, Vrieze, S, Ahluwalia, TS, Akiyama, M, Allison, MA, Alvarez, M, Andersen, MK, Ani, A, Appadurai, V, Arbeeva, L, Bhaskar, S, Bielak, LF, Bollepalli, S, Bonnycastle, LL, Bork-Jensen, J, Bradfield, JP, Bradford, Y, Braund, PS, Brody, JA, Burgdorf, KS, Cade, BE, Cai, H, Cai, Q, Campbell, A, Canadas-Garre, M, Catamo, E, Chai, J-F, Chai, X, Chang, L-C, Chang, Y-C, Chen, C-H, Chesi, A, Choi, SH, Chung, R-H, Cocca, M, Concas, MP, Couture, C, Cuellar-Partida, G, Danning, R, Daw, EW, Degenhard, F, Delgado, GE, Delitala, A, Demirkan, A, Deng, X, Devineni, P, Dietl, A, Dimitriou, M, Dimitrov, L, Dorajoo, R, Ekici, AB, Engmann, JE, Fairhurst-Hunter, Z, Farmaki, A-E, Faul, JD, Fernandez-Lopez, J-C, Forer, L, Francescatto, M, Freitag-Wolf, S, Fuchsberger, C, Galesloot, TE, Gao, Y, Gao, Z, Geller, F, Giannakopoulou, O, Giulianini, F, Gjesing, AP, Goel, A, Gordon, SD, Gorski, M, Grove, J, Guo, X, Gustafsson, S, Haessler, J, Hansen, TF, Havulinna, AS, Haworth, SJ, He, J, Heard-Costa, N, Hebbar, P, Hindy, G, Ho, Y-LA, Hofer, E, Holliday, E, Horn, K, Hornsby, WE, Hottenga, J-J, Huang, H, Huang, J, Huerta-Chagoya, A, Huffman, JE, Hung, Y-J, Huo, S, Hwang, MY, Iha, H, Ikeda, DD, Isono, M, Jackson, AU, Jager, S, Jansen, IE, Johansson, I, Jonas, JB, Jonsson, A, Jorgensen, T, Kalafati, I-P, Kanai, M, Kanoni, S, Karhus, LL, Kasturiratne, A, Katsuya, T, Kawaguchi, T, Kember, RL, Kentistou, KA, Kim, H-N, Kim, YJ, Kleber, ME, Knol, MJ, Kurbasic, A, Lauzon, M, Le, P, Lea, R, Lee, J-Y, Leonard, HL, Li, SA, Li, X, Liang, J, Lin, H, Lin, S-Y, Liu, J, Liu, X, Lo, KS, Long, J, Lores-Motta, L, Luan, J, Lyssenko, V, Lyytikainen, L-P, Mahajan, A, Mamakou, V, Mangino, M, Manichaikul, A, Marten, J, Mattheisen, M, Mavarani, L, McDaid, AF, Meidtner, K, Melendez, TL, Mercader, JM, Milaneschi, Y, Miller, JE, Millwood, IY, Mishra, PP, Mitchell, RE, Mollehave, LT, Morgan, A, Mucha, S, Munz, M, Nakatochi, M, Nelson, CP, Nethander, M, Nho, CW, Nielsen, AA, Nolte, IM, Nongmaithem, SS, Noordam, R, Ntalla, I, Nutile, T, Pandit, A, Christofidou, P, Parna, K, Pauper, M, Petersen, ERB, Petersen, L, Pitkanen, N, Polasek, O, Poveda, A, Preuss, MH, Pyarajan, S, Raffield, LM, Rakugi, H, Ramirez, J, Rasheed, A, Raven, D, Rayner, NW, Riveros, C, Rohde, R, Ruggiero, D, Ruotsalainen, SE, Ryan, KA, Sabater-Lleal, M, Saxena, R, Scholz, M, Sendamarai, A, Shen, B, Shi, J, Shin, JH, Sidore, C, Sitlani, CM, Slieker, RKC, Smit, RAJ, Smith, A, Smith, JA, Smyth, LJ, Southam, LE, Steinthorsdottir, V, Sun, L, Takeuchi, F, Tallapragada, D, Taylor, KD, Tayo, BO, Tcheandjieu, C, Terzikhan, N, Tesolin, P, Teumer, A, Theusch, E, Thompson, DJ, Thorleifsson, G, Timmers, PRHJ, Trompet, S, Turman, C, Vaccargiu, S, van der Laan, SW, van der Most, PJ, van Klinken, JB, van Setten, J, Verma, SS, Verweij, N, Veturi, Y, Wang, CA, Wang, C, Wang, L, Wang, Z, Warren, HR, Wei, WB, Wickremasinghe, AR, Wielscher, M, Wiggins, KL, Winsvold, BS, Wong, A, Wu, Y, Wuttke, M, Xia, R, Xie, T, Yamamoto, K, Yang, J, Yao, J, Young, H, Yousri, NA, Yu, L, Zeng, L, Zhang, W, Zhang, X, Zhao, J-H, Zhao, W, Zhou, W, Zimmermann, ME, Zoledziewska, M, Adair, LS, Adams, HHH, Aguilar-Salinas, CA, Al-Mulla, F, Arnett, DK, Asselbergs, FW, Asvold, BO, Attia, J, Banas, B, Bandinelli, S, Bennett, DA, Bergler, T, Bharadwaj, D, Biino, G, Bisgaard, H, Boerwinkle, E, Boger, CA, Bonnelykke, K, Boomsma, D, Borglum, AD, Borja, JB, Bouchard, C, Bowden, DW, Brandslund, I, Brumpton, B, Buring, JE, Caulfield, MJ, Chambers, JC, Chandak, GR, Chanock, SJ, Chaturvedi, N, Chen, Y-DI, Chen, Z, Cheng, C-Y, Christophersen, IE, Ciullo, M, Cole, JW, Collins, FS, Cooper, RS, Cruz, M, Cucca, F, Cupples, LA, Cutler, MJ, Damrauer, SM, Dantoft, TM, de Borst, GJ, de Groot, LCPGM, De Jager, PL, de Kleijn, DP, de Silva, HJ, Dedoussis, G, den Hollander, A, Du, S, Easton, DF, Elders, PJM, Eliassen, AH, Ellinor, PT, Elmstahl, S, Erdmann, J, Evans, MK, Fatkin, D, Feenstra, B, Feitosa, MF, Ferrucci, L, Ford, I, Fornage, M, Franke, A, Franks, PW, Freedman, B, Gasparini, P, Gieger, C, Girotto, G, Goddard, ME, Golightly, YM, Gonzalez-Villalpando, C, Gordon-Larsen, P, Grallert, H, Grant, SFA, Grarup, N, Griffiths, L, Gudnason, V, Haiman, C, Hakonarson, H, Hansen, T, Hartman, CA, Hattersley, AT, Hayward, C, Heckbert, SR, Heng, C-K, Hengstenberg, C, Hewitt, AW, Hishigaki, H, Hoyng, CB, Huang, PL, Huang, W, Hunt, SC, Hveem, K, Hypponen, E, Iacono, WG, Ichihara, S, Ikram, MA, Isasi, CR, Jackson, RD, Jarvelin, M-R, Jin, Z-B, Jockel, K-H, Joshi, PK, Jousilahti, P, Jukema, JW, Kahonen, M, Kamatani, Y, Kang, KD, Kaprio, J, Kardia, SLR, Karpe, F, Kato, N, Kee, F, Kessler, T, Khera, A, Khor, CC, Kiemeney, LALM, Kim, B-J, Kim, EK, Kim, H-L, Kirchhof, P, Kivimaki, M, Koh, W-P, Koistinen, HA, Kolovou, GD, Kooner, JS, Kooperberg, C, Kottgen, A, Kovacs, P, Kraaijeveld, A, Kraft, P, Krauss, RM, Kumari, M, Kutalik, Z, Laakso, M, Lange, LA, Langenberg, C, Launer, LJ, Le Marchand, L, Lee, H, Lee, NR, Lehtimaki, T, Li, H, Li, L, Lieb, W, Lin, X, Lind, L, Linneberg, A, Liu, C-T, Loeffler, M, London, B, Lubitz, SA, Lye, SJ, Mackey, DA, Magi, R, Magnusson, PKE, Marcus, GM, Vidal, PM, Martin, NG, Marz, W, Matsuda, F, McGarrah, RW, McGue, M, McKnight, AJ, Medland, SE, Mellstrom, D, Metspalu, A, Mitchell, BD, Mitchell, P, Mook-Kanamori, DO, Morris, AD, Mucci, LA, Munroe, PB, Nalls, MA, Nazarian, S, Nelson, AE, Neville, MJ, Newton-Cheh, C, Nielsen, CS, Nothen, MM, Ohlsson, C, Oldehinkel, AJ, Orozco, L, Pahkala, K, Pajukanta, P, Palmer, CNA, Parra, EJ, Pattaro, C, Pedersen, O, Pennell, CE, Penninx, BWJH, Perusse, L, Peters, A, Peyser, PA, Porteous, DJ, Posthuma, D, Power, C, Pramstaller, PP, Province, MA, Qi, Q, Qu, J, Rader, DJ, Raitakari, OT, Ralhan, S, Rallidis, LS, Rao, DC, Redline, S, Reilly, DF, Reiner, AP, Rhee, SY, Ridker, PM, Rienstra, M, Ripatti, S, Ritchie, MD, Roden, DM, Rosendaal, FR, Rotter, J, Rudan, I, Rutters, F, Sabanayagam, C, Saleheen, D, Salomaa, V, Samani, NJ, Sanghera, DK, Sattar, N, Schmidt, B, Schmidt, H, Schmidt, R, Schulze, MB, Schunkert, H, Scott, LJ, Scott, RJ, Sever, P, Shiroma, EJ, Shoemaker, MB, Shu, X-O, Simonsick, EM, Sims, M, Singh, JR, Singleton, AB, Sinner, MF, Smith, JG, Snieder, H, Spector, TD, Stampfer, MJ, Stark, KJ, Strachan, DP, t' Hart, LM, Tabara, Y, Tang, H, Tardif, J-C, Thanaraj, TA, Timpson, NJ, Tonjes, A, Tremblay, A, Tuomi, T, Tuomilehto, J, Tusie-Luna, M-T, Uitterlinden, AG, van Dam, RM, van der Harst, P, Van der Velde, N, van Duijn, CM, van Schoor, NM, Vitart, V, Volker, U, Vollenweider, P, Volzke, H, Wacher-Rodarte, NH, Walker, M, Wang, YX, Wareham, NJ, Watanabe, RM, Watkins, H, Weir, DR, Werge, TM, Widen, E, Wilkens, LR, Willemsen, G, Willett, WC, Wilson, JF, Wong, T-Y, Woo, J-T, Wright, AF, Wu, J-Y, Xu, H, Yajnik, CS, Yokota, M, Yuan, J-M, Zeggini, E, Zemel, BS, Zheng, W, Zhu, X, Zmuda, JM, Zonderman, AB, Zwart, J-A, Chasman, D, Cho, YS, Heid, IM, McCarthy, M, Ng, MCY, O'Donnell, CJ, Rivadeneira, F, Thorsteinsdottir, U, Sun, Y, Tai, ES, Boehnke, M, Deloukas, P, Justice, AE, Lindgren, CM, Loos, RJF, Mohlke, KL, North, KE, Stefansson, K, Walters, RG, Winkler, TW, Young, KL, Loh, P-R, Esko, T, Assimes, TL, Auton, A, Abecasis, GR, Willer, CJ, Locke, AE, Berndt, S, Lettre, G, Frayling, TM, Okada, Y, Wood, AR, Visscher, PM, and Hirschhorn, JN
Abstract: Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
Published: 2022

11. Stroke genetics informs drug discovery and risk prediction across ancestries (vol 611, pg 115, 2022)

Author: Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, Debette, S, Mishra, A, Malik, R, Hachiya, T, Jurgenson, T, Namba, S, Posner, DC, Kamanu, FK, Koido, M, Le Grand, Q, Shi, M, He, Y, Georgakis, MK, Caro, I, Krebs, K, Liaw, Y-C, Vaura, FC, Lin, K, Winsvold, BS, Srinivasasainagendra, V, Parodi, L, Bae, H-J, Chauhan, G, Chong, MR, Tomppo, L, Akinyemi, R, Roshchupkin, GV, Habib, N, Jee, YH, Thomassen, JQ, Abedi, V, Carcel-Marquez, J, Nygaard, M, Leonard, HL, Yang, C, Yonova-Doing, E, Knol, MJ, Lewis, AJ, Judy, RL, Ago, T, Amouyel, P, Armstrong, ND, Bakker, MK, Bartz, TM, Bennett, DA, Bis, JC, Bordes, C, Borte, S, Cain, A, Ridker, PM, Cho, K, Chen, Z, Cruchaga, C, Cole, JW, de Jager, PL, de Cid, R, Endres, M, Ferreira, LE, Geerlings, MI, Gasca, NC, Gudnason, V, Hata, J, He, J, Heath, AK, Ho, Y-L, Havulinna, AS, Hopewell, JC, Hyacinth, IH, Inouye, M, Jacob, MA, Jeon, CE, Jern, C, Kamouchi, M, Keene, KL, Kitazono, T, Kittner, SJ, Konuma, T, Kumar, A, Lacaze, P, Launer, LJ, Lee, K-J, Lepik, K, Li, J, Li, L, Manichaikul, A, Markus, HS, Marston, NA, Meitinger, T, Mitchell, BD, Montellano, FA, Morisaki, T, Mosley, TH, Nalls, MA, Nordestgaard, BG, O'Donnell, MJ, Okada, Y, Onland-Moret, NC, Ovbiagele, B, Peters, A, Psaty, BM, Rich, SS, Rosand, J, Sabatine, MS, Sacco, RL, Saleheen, D, Sandset, EC, Salomaa, V, Sargurupremraj, M, Sasaki, M, Satizabal, CL, Schmidt, CO, Shimizu, A, Smith, NL, Sloane, KL, Sutoh, Y, Sun, YV, Tanno, K, Tiedt, S, Tatlisumak, T, Torres-Aguila, NP, Tiwari, HK, Tregouet, D-A, Trompet, S, Tuladhar, AM, Tybjaerg-Hansen, A, van Vugt, M, Vibo, R, Verma, SS, Wiggins, KL, Wennberg, P, Woo, D, Wilson, PWF, Xu, H, Yang, Q, Yoon, K, Millwood, IY, Gieger, C, Ninomiya, T, Grabe, HJ, Jukema, JW, Rissanen, IL, Strbian, D, Kim, YJ, Chen, P-H, Mayerhofer, E, Howson, JMM, Irvin, MR, Adams, H, Wassertheil-Smoller, S, Christensen, K, Ikram, MA, Rundek, T, Worrall, BB, Lathrop, GM, Riaz, M, Simonsick, EM, Korv, J, Franca, PHC, Zand, R, Prasad, K, Frikke-Schmidt, R, de Leeuw, F-E, Liman, T, Haeusler, KG, Ruigrok, YM, Heuschmann, PU, Longstreth, WT, Jung, KJ, Bastarache, L, Pare, G, Damrauer, SM, Chasman, DI, Rotter, JI, Anderson, CD, Zwart, J-A, Niiranen, TJ, Fornage, M, Liaw, Y-P, Seshadri, S, Fernandez-Cadenas, I, Walters, RG, Ruff, CT, Owolabi, MO, Huffman, JE, Milani, L, Kamatani, Y, Dichgans, M, and Debette, S
Published: 2022

12. Large-scale genomic analysis of renal cell carcinoma using 1,532 Japanese patients and 5,996 controls

Author: Sekine, Y., primary, Iwasaki, Y., additional, Aoi, T., additional, Mikiko, E., additional, Hirata, M., additional, Kamatani, Y., additional, Matsuda, K., additional, Kokichi, S., additional, Yoshida, T., additional, Murakami, Y., additional, Fukui, T., additional, Akamatsu, S., additional, Ogawa, O., additional, Nakagawa, H., additional, Numakura, K., additional, Narita, S., additional, Momozawa, Y., additional, and Habuchi, T., additional
Published: 2022
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13. Trans-ethnic genome-wide association study reveals new therapeutic targets for benign prostatic hyperplasia

Author: Ng, M., primary, Matsuda, K., additional, Tanikawa, C., additional, Terao, C., additional, Kamatani, Y., additional, Wei, W., additional, Auton, A., additional, Turney, B.W., additional, Bryant, R.J., additional, and Furniss, D., additional
Published: 2022
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14. A1124 - Large-scale genomic analysis of renal cell carcinoma using 1,532 Japanese patients and 5,996 controls

Author: Sekine, Y., Iwasaki, Y., Aoi, T., Mikiko, E., Hirata, M., Kamatani, Y., Matsuda, K., Kokichi, S., Yoshida, T., Murakami, Y., Fukui, T., Akamatsu, S., Ogawa, O., Nakagawa, H., Numakura, K., Narita, S., Momozawa, Y., and Habuchi, T.
Published: 2022
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15. IDENTIFICATION OF SOMATIC MUTATIONS IN PATIENTS WITH ANCA-ASSOCIATED VASCULITIS.

Author: Iwasaki, T., Ohmura, K., Endo, C., Shirakashi, M., Hiwa, R., Tsuji, H., Kitagori, K., Akizuki, S., Nakashima, R., Yoshifuji, H., Morinobu, A., Matsuda, F., and Kamatani, Y.
Published: 2023
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16. Dissecting the Shared Genetic Architecture of Suicide Attempt, Psychiatric Disorders, and Known Risk Factors

Author: Niamh Mullins, JooEun Kang, Adrian I. Campos, Jonathan R.I. Coleman, Alexis C. Edwards, Hanga Galfalvy, Daniel F. Levey, Adriana Lori, Andrey Shabalin, Anna Starnawska, Mei-Hsin Su, Hunna J. Watson, Mark Adams, Swapnil Awasthi, Michael Gandal, Jonathan D. Hafferty, Akitoyo Hishimoto, Minsoo Kim, Satoshi Okazaki, Ikuo Otsuka, Stephan Ripke, Erin B. Ware, Andrew W. Bergen, Wade H. Berrettini, Martin Bohus, Harry Brandt, Xiao Chang, Wei J. Chen, Hsi-Chung Chen, Steven Crawford, Scott Crow, Emily DiBlasi, Philibert Duriez, Fernando Fernández-Aranda, Manfred M. Fichter, Steven Gallinger, Stephen J. Glatt, Philip Gorwood, Yiran Guo, Hakon Hakonarson, Katherine A. Halmi, Hai-Gwo Hwu, Sonia Jain, Stéphane Jamain, Susana Jiménez-Murcia, Craig Johnson, Allan S. Kaplan, Walter H. Kaye, Pamela K. Keel, James L. Kennedy, Kelly L. Klump, Dong Li, Shih-Cheng Liao, Klaus Lieb, Lisa Lilenfeld, Chih-Min Liu, Pierre J. Magistretti, Christian R. Marshall, James E. Mitchell, Eric T. Monson, Richard M. Myers, Dalila Pinto, Abigail Powers, Nicolas Ramoz, Stefan Roepke, Vsevolod Rozanov, Stephen W. Scherer, Christian Schmahl, Marcus Sokolowski, Michael Strober, Laura M. Thornton, Janet Treasure, Ming T. Tsuang, Stephanie H. Witt, D. Blake Woodside, Zeynep Yilmaz, Lea Zillich, Rolf Adolfsson, Ingrid Agartz, Tracy M. Air, Martin Alda, Lars Alfredsson, Ole A. Andreassen, Adebayo Anjorin, Vivek Appadurai, María Soler Artigas, Sandra Van der Auwera, M. Helena Azevedo, Nicholas Bass, Claiton H.D. Bau, Bernhard T. Baune, Frank Bellivier, Klaus Berger, Joanna M. Biernacka, Tim B. Bigdeli, Elisabeth B. Binder, Michael Boehnke, Marco P. Boks, Rosa Bosch, David L. Braff, Richard Bryant, Monika Budde, Enda M. Byrne, Wiepke Cahn, Miguel Casas, Enrique Castelao, Jorge A. Cervilla, Boris Chaumette, Sven Cichon, Aiden Corvin, Nicholas Craddock, David Craig, Franziska Degenhardt, Srdjan Djurovic, Howard J. Edenberg, Ayman H. Fanous, Jerome C. Foo, Andreas J. Forstner, Mark Frye, Janice M. Fullerton, Justine M. Gatt, Pablo V. Gejman, Ina Giegling, Hans J. Grabe, Melissa J. Green, Eugenio H. Grevet, Maria Grigoroiu-Serbanescu, Blanca Gutierrez, Jose Guzman-Parra, Steven P. Hamilton, Marian L. Hamshere, Annette Hartmann, Joanna Hauser, Stefanie Heilmann-Heimbach, Per Hoffmann, Marcus Ising, Ian Jones, Lisa A. Jones, Lina Jonsson, René S. Kahn, John R. Kelsoe, Kenneth S. Kendler, Stefan Kloiber, Karestan C. Koenen, Manolis Kogevinas, Bettina Konte, Marie-Odile Krebs, Mikael Landén, Jacob Lawrence, Marion Leboyer, Phil H. Lee, Douglas F. Levinson, Calwing Liao, Jolanta Lissowska, Susanne Lucae, Fermin Mayoral, Susan L. McElroy, Patrick McGrath, Peter McGuffin, Andrew McQuillin, Sarah E. Medland, Divya Mehta, Ingrid Melle, Yuri Milaneschi, Philip B. Mitchell, Esther Molina, Gunnar Morken, Preben Bo Mortensen, Bertram Müller-Myhsok, Caroline Nievergelt, Vishwajit Nimgaonkar, Markus M. Nöthen, Michael C. O’Donovan, Roel A. Ophoff, Michael J. Owen, Carlos Pato, Michele T. Pato, Brenda W.J.H. Penninx, Jonathan Pimm, Giorgio Pistis, James B. Potash, Robert A. Power, Martin Preisig, Digby Quested, Josep Antoni Ramos-Quiroga, Andreas Reif, Marta Ribasés, Vanesa Richarte, Marcella Rietschel, Margarita Rivera, Andrea Roberts, Gloria Roberts, Guy A. Rouleau, Diego L. Rovaris, Dan Rujescu, Cristina Sánchez-Mora, Alan R. Sanders, Peter R. Schofield, Thomas G. Schulze, Laura J. Scott, Alessandro Serretti, Jianxin Shi, Stanley I. Shyn, Lea Sirignano, Pamela Sklar, Olav B. Smeland, Jordan W. Smoller, Edmund J.S. Sonuga-Barke, Gianfranco Spalletta, John S. Strauss, Beata Świątkowska, Maciej Trzaskowski, Gustavo Turecki, Laura Vilar-Ribó, John B. Vincent, Henry Völzke, James T.R. Walters, Cynthia Shannon Weickert, Thomas W. Weickert, Myrna M. Weissman, Leanne M. Williams, Naomi R. Wray, Clement C. Zai, Allison E. Ashley-Koch, Jean C. Beckham, Elizabeth R. Hauser, Michael A. Hauser, Nathan A. Kimbrel, Jennifer H. Lindquist, Benjamin McMahon, David W. Oslin, Xuejun Qin, Esben Agerbo, Anders D. Børglum, Gerome Breen, Annette Erlangsen, Tõnu Esko, Joel Gelernter, David M. Hougaard, Ronald C. Kessler, Henry R. Kranzler, Qingqin S. Li, Nicholas G. Martin, Andrew M. McIntosh, Ole Mors, Merete Nordentoft, Catherine M. Olsen, David Porteous, Robert J. Ursano, Danuta Wasserman, Thomas Werge, David C. Whiteman, Cynthia M. Bulik, Hilary Coon, Ditte Demontis, Anna R. Docherty, Po-Hsiu Kuo, Cathryn M. Lewis, J. John Mann, Miguel E. Rentería, Daniel J. Smith, Eli A. Stahl, Murray B. Stein, Fabian Streit, Virginia Willour, Douglas M. Ruderfer, Manuel Mattheisen, Abdel Abdellaoui, Mark J. Adams, Till F.M. Andlauer, Silviu-Alin Bacanu, Marie Bækvad-Hansen, Aartjan T.F. Beekman, Julien Bryois, Henriette N. Buttenschøn, Jonas Bybjerg-Grauholm, Na Cai, Jane Hvarregaard Christensen, Toni-Kim Clarke, Lucía Colodro-Conde, Baptiste Couvy-Duchesne, Nick Craddock, Gregory E. Crawford, Gail Davies, Eske M. Derks, Nese Direk, Conor V. Dolan, Erin C. Dunn, Thalia C. Eley, Valentina Escott-Price, Farnush Farhadi Hassan Kiadeh, Hilary K. Finucane, Josef Frank, Héléna A. Gaspar, Michael Gill, Fernando S. Goes, Scott D. Gordon, Shantel Marie Weinsheimer, Jürgen Wellmann, Gonneke Willemsen, Yang Wu, Hualin S. Xi, Jian Yang, Futao Zhang, Volker Arolt, Dorret I. Boomsma, Udo Dannlowski, E.J.C. de Geus, J. Raymond Depaulo, Enrico Domenici, Katharina Domschke, Jakob Grove, Lynsey S. Hall, Christine Søholm Hansen, Thomas F. Hansen, Stefan Herms, Ian B. Hickie, Georg Homuth, Carsten Horn, Jouke-Jan Hottenga, David M. Howard, Rick Jansen, Eric Jorgenson, James A. Knowles, Isaac S. Kohane, Julia Kraft, Warren W. Kretzschmar, Zoltán Kutalik, Yihan Li, Penelope A. Lind, Donald J. MacIntyre, Dean F. MacKinnon, Robert M. Maier, Wolfgang Maier, Jonathan Marchini, Hamdi Mbarek, Christel M. Middeldorp, Evelin Mihailov, Lili Milani, Francis M. Mondimore, Grant W. Montgomery, Sara Mostafavi, Matthias Nauck, Bernard Ng, Michel G. Nivard, Dale R. Nyholt, Paul F. O’Reilly, Hogni Oskarsson, Caroline Hayward, Andrew C. Heath, Glyn Lewis, Pamela A.F. Madden, Patrik K. Magnusson, Andres Metspalu, Sara A. Paciga, Nancy L. Pedersen, Jodie N. Painter, Carsten Bøcker Pedersen, Marianne Giørtz Pedersen, Roseann E. Peterson, Wouter J. Peyrot, Danielle Posthuma, Jorge A. Quiroz, Per Qvist, John P. Rice, Brien P. Riley, Saira Saeed Mirza, Robert Schoevers, Eva C. Schulte, Ling Shen, Engilbert Sigurdsson, Grant C.B. Sinnamon, Johannes H. Smit, Hreinn Stefansson, Stacy Steinberg, Jana Strohmaier, Katherine E. Tansey, Henning Teismann, Alexander Teumer, Wesley Thompson, Pippa A. Thomson, Thorgeir E. Thorgeirsson, Matthew Traylor, Jens Treutlein, Vassily Trubetskoy, André G. Uitterlinden, Daniel Umbricht, Albert M. van Hemert, Alexander Viktorin, Peter M. Visscher, Yunpeng Wang, Bradley T. Webb, Roy H. Perlis, David J. Porteous, Catherine Schaefer, Kari Stefansson, Henning Tiemeier, Rudolf Uher, Patrick F. Sullivan, Kevin S. O’Connell, Brandon Coombes, Zhen Qiao, Thomas D. Als, Sigrid Børte, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, Nolan Kamitaki, Kristi Krebs, Georgia Panagiotaropoulou, Brian M. Schilder, Laura G. Sloofman, Bendik S. Winsvold, Hong-Hee Won, Liliya Abramova, Kristina Adorjan, Mariam Al Eissa, Diego Albani, Ney Alliey-Rodriguez, Verneri Antilla, Anastasia Antoniou, Ji Hyun Baek, Michael Bauer, Eva C. Beins, Sarah E. Bergen, Armin Birner, Erlend Bøen, Murielle Brum, Ben M. Brumpton, Nathalie Brunkhorst-Kanaan, William Byerley, Murray Cairns, Miquel Casas, Pablo Cervantes, Cristiana Cruceanu, Alfredo Cuellar-Barboza, Julie Cunningham, David Curtis, Piotr M. Czerski, Anders M. Dale, Nina Dalkner, Friederike S. David, Amanda L. Dobbyn, Athanassios Douzenis, Torbjørn Elvsåshagen, I. Nicol Ferrier, Alessia Fiorentino, Tatiana M. Foroud, Liz Forty, Oleksandr Frei, Nelson B. Freimer, Louise Frisén, Katrin Gade, Julie Garnham, Ian R. Gizer, Katherine Gordon-Smith, Tiffany A. Greenwood, José Guzman-Parra, Kyooseob Ha, Magnus Haraldsson, Martin Hautzinger, Urs Heilbronner, Dennis Hellgren, Peter A. Holmans, Laura Huckins, Jessica S. Johnson, Janos L. Kalman, Yoichiro Kamatani, Sarah Kittel-Schneider, Maria Koromina, Thorsten M. Kranz, Michiaki Kubo, Ralph Kupka, Steven A. Kushner, Catharina Lavebratt, Markus Leber, Heon-Jeong Lee, Shawn E. Levy, Catrin Lewis, Martin Lundberg, Sigurdur H. Magnusson, Adam Maihofer, Dolores Malaspina, Eirini Maratou, Lina Martinsson, Nathaniel W. McGregor, James D. McKay, Helena Medeiros, Vincent Millischer, Jennifer L. Moran, Derek W. Morris, Thomas W. Mühleisen, Niamh O’Brien, Claire O’Donovan, Loes M. Olde Loohuis, Lilijana Oruc, Sergi Papiol, Antonio F. Pardiñas, Amy Perry, Andrea Pfennig, Evgenia Porichi, Towfique Raj, Mark H. Rapaport, J. Raymond DePaulo, Eline J. Regeer, Fabio Rivas, Julian Roth, Panos Roussos, Fanny Senner, Sally Sharp, Paul D. Shilling, Claire Slaney, Janet L. Sobell, Maria Soler Artigas, Anne T. Spijker, Dan J. Stein, Chikashi Terao, Claudio Toma, Paul Tooney, Evangelia-Eirini Tsermpini, Marquis P. Vawter, Helmut Vedder, Simon Xi, Wei Xu, Jessica Mei Kay Yang, Allan H. Young, Hannah Young, Peter P. Zandi, Hang Zhou, null HUNT All-In Psychiatry, Gulja Babadjanova, Lena Backlund, Susanne Bengesser, Douglas H.R. Blackwood, Vaughan J. Carr, Stanley Catts, Dimitris Dikeos, Bruno Etain, Panagiotis Ferentinos, Micha Gawlik, Elliot S. Gershon, Frans Henskens, Jan Hillert, Kyung Sue Hong, Christina M. Hultman, Kristian Hveem, Nakao Iwata, Assen V. Jablensky, George Kirov, Christine Lochner, Carmel Loughland, Carol A. Mathews, Francis J. McMahon, Patricia Michie, Bryan Mowry, Benjamin M. Neale, Caroline M. Nievergelt, Ketil J. Oedegaard, Tomas Olsson, Chris Pantelis, George P. Patrinos, Eva Z. Reininghaus, Takeo Saito, Ulrich Schall, Martin Schalling, Rodney J. Scott, Eystein Stordal, Arne E. Vaaler, Eduard Vieta, Irwin D. Waldman, John-Anker Zwart, John I. Nurnberger, Arianna Di Florio, Roger A.H. Adan, Tetsuya Ando, Harald Aschauer, Jessica H. Baker, Vladimir Bencko, Andreas Birgegård, Joseph M. Boden, Ilka Boehm, Claudette Boni, Vesna Boraska Perica, Katharina Buehren, Roland Burghardt, Laura Carlberg, Matteo Cassina, Maurizio Clementi, Roger D. Cone, Philippe Courtet, James J. Crowley, Unna N. Danner, Oliver S.P. Davis, Martina de Zwaan, George Dedoussis, Daniela Degortes, Janiece E. DeSocio, Danielle M. Dick, Christian Dina, Monika Dmitrzak-Weglarz, Elisa Docampo Martinez, Laramie E. Duncan, Karin Egberts, Morten Mattingsdal, Sara McDevitt, Ingrid Meulenbelt, Nadia Micali, James Mitchell, Karen Mitchell, Palmiero Monteleone, Alessio Maria Monteleone, Melissa A. Munn-Chernoff, Benedetta Nacmias, Marie Navratilova, Ioanna Ntalla, Julie K. O’Toole, Leonid Padyukov, Aarno Palotie, Jacques Pantel, Hana Papezova, Richard Parker, John F. Pearson, Stefan Ehrlich, Geòrgia Escaramís, Thomas Espeseth, Xavier Estivill, Anne Farmer, Angela Favaro, Krista Fischer, James A.B. Floyd, Manuel Föcker, Lenka Foretova, Monica Forzan, Christopher S. Franklin, Giovanni Gambaro, Johanna Giuranna, Paola Giusti-Rodríquez, Fragiskos Gonidakis, Scott Gordon, Monica Gratacos Mayora, Sébastien Guillaume, Ken B. Hanscombe, Konstantinos Hatzikotoulas, Johannes Hebebrand, Sietske G. Helder, Anjali K. Henders, Beate Herpertz-Dahlmann, Wolfgang Herzog, Anke Hinney, L. John Horwood, Christopher Hübel, Liselotte V. Petersen, Kirstin L. Purves, Anu Raevuori, Ted Reichborn-Kjennerud, Valdo Ricca, Samuli Ripatti, Franziska Ritschel, Marion Roberts, Filip Rybakowski, Paolo Santonastaso, André Scherag, Ulrike Schmidt, Nicholas J. Schork, Alexandra Schosser, Jochen Seitz, Lenka Slachtova, P. Eline Slagboom, Margarita C.T. Slof-Op ‘t Landt, Agnieszka Slopien, Nicole Soranzo, Sandro Sorbi, Lorraine Southam, Vidar W. Steen, Laura M. Huckins, James I. Hudson, Hartmut Imgart, Hidetoshi Inoko, Vladimir Janout, Jennifer Jordan, Antonio Julià, Gursharan Kalsi, Deborah Kaminská, Jaakko Kaprio, Leila Karhunen, Andreas Karwautz, Martien J.H. Kas, Martin A. Kennedy, Anna Keski-Rahkonen, Kirsty Kiezebrink, Youl-Ri Kim, Katherine M. Kirk, Lars Klareskog, Gun Peggy S. Knudsen, Janne T. Larsen, Stephanie Le Hellard, Virpi M. Leppä, Paul Lichtenstein, Bochao Danae Lin, Astri Lundervold, Jurjen Luykx, Mario Maj, Katrin Mannik, Sara Marsal, Garret D. Stuber, Jin P. Szatkiewicz, Ioanna Tachmazidou, Elena Tenconi, Alfonso Tortorella, Federica Tozzi, Artemis Tsitsika, Marta Tyszkiewicz-Nwafor, Konstantinos Tziouvas, Annemarie A. van Elburg, Eric F. van Furth, Tracey D. Wade, Gudrun Wagner, Esther Walton, H. Erich Wichmann, Elisabeth Widen, Shuyang Yao, Eleftheria Zeggini, Stephanie Zerwas, Stephan Zipfel, Martin Jungkunz, Lydie Dietl, Cornelia E. Schwarze, Norbert Dahmen, Björn H. Schott, Arian Mobascher, Silvia Crivelli, Michelle F. Dennis, Phillip D. Harvey, Bruce W. Carter, Jennifer E. Huffman, Daniel Jacobson, Ravi Madduri, Maren K. Olsen, John Pestian, J. Michael Gaziano, Sumitra Muralidhar, Rachel Ramoni, Jean Beckham, Kyong-Mi Chang, Christopher J. O’Donnell, Philip S. Tsao, James Breeling, Grant Huang, J.P. Casas Romero, Jennifer Moser, Stacey B. Whitbourne, Jessica V. Brewer, Mihaela Aslan, Todd Connor, Dean P. Argyres, Brady Stephens, Mary T. Brophy, Donald E. Humphries, Luis E. Selva, Nhan Do, Shahpoor Shayan, Kelly Cho, Saiju Pyarajan, Elizabeth Hauser, Yan Sun, Hongyu Zhao, Peter Wilson, Rachel McArdle, Louis Dellitalia, Kristin Mattocks, John Harley, Clement J. Zablocki, Jeffrey Whittle, Frank Jacono, Salvador Gutierrez, Gretchen Gibson, Kimberly Hammer, Laurence Kaminsky, Gerardo Villareal, Scott Kinlay, Junzhe Xu, Mark Hamner, Roy Mathew, Sujata Bhushan, Pran Iruvanti, Michael Godschalk, Zuhair Ballas, Douglas Ivins, Stephen Mastorides, Jonathan Moorman, Saib Gappy, Jon Klein, Nora Ratcliffe, Hermes Florez, Olaoluwa Okusaga, Maureen Murdoch, Peruvemba Sriram, Shing Shing Yeh, Neeraj Tandon, Darshana Jhala, Samuel Aguayo, David Cohen, Satish Sharma, Suthat Liangpunsakul, Kris Ann Oursler, Mary Whooley, Sunil Ahuja, Joseph Constans, Paul Meyer, Jennifer Greco, Michael Rauchman, Richard Servatius, Melinda Gaddy, Agnes Wallbom, Timothy Morgan, Todd Stapley, Scott Sherman, George Ross, Philip Tsao, Patrick Strollo, Edward Boyko, Laurence Meyer, Samir Gupta, Mostaqul Huq, Joseph Fayad, Adriana Hung, Jack Lichy, Robin Hurley, Brooks Robey, Robert Striker, Dietl, Lydie, Schwarze, Cornelia E., Dahmen, Norbert, Schott, Björn H., Nöthen, Markus M., Ripke, Stephan, Mobascher, Arian, Rujescu, Dan, Lieb, Klaus, Roepke, Stefan, Schmahl, Christian, Bohus, Martin, Rietschel, Marcella, Crivelli, Silvia, Dennis, Michelle F., Harvey, Phillip D., Carter, Bruce W., Huffman, Jennifer E., Jacobson, Daniel, Madduri, Ravi, Olsen, Maren K., Pestian, John, Gaziano, J. Michael, Muralidhar, Sumitra, Ramoni, Rachel, Beckham, Jean, Chang, Kyong-Mi, O'Donnell, Christopher J., Tsao, Philip S., Breeling, James, Huang, Grant, Romero, J. P. Casas, Moser, Jennifer, Whitbourne, Stacey B., Brewer, Jessica V., Aslan, Mihaela, Connor, Todd, Argyres, Dean P., Stephens, Brady, Brophy, Mary T., Humphries, Donald E., Selva, Luis E., Do, Nhan, Shayan, Shahpoor, Cho, Kelly, Pyarajan, Saiju, Hauser, Elizabeth, Sun, Yan, Zhao, Hongyu, Wilson, Peter, McArdle, Rachel, Dellitalia, Louis, Mattocks, Kristin, Harley, John, Zablocki, Clement J., Whittle, Jeffrey, Jacono, Frank, Gutierrez, Salvador, Gibson, Gretchen, Hammer, Kimberly, Kaminsky, Laurence, Villareal, Gerardo, Kinlay, Scott, Xu, Junzhe, Hamner, Mark, Mathew, Roy, Bhushan, Sujata, Iruvanti, Pran, Godschalk, Michael, Ballas, Zuhair, Ivins, Douglas, Mastorides, Stephen, Moorman, Jonathan, Gappy, Saib, Klein, Jon, Ratcliffe, Nora, Florez, Hermes, Okusaga, Olaoluwa, Murdoch, Maureen, Sriram, Peruvemba, Yeh, Shing Shing, Tandon, Neeraj, Jhala, Darshana, Aguayo, Samuel, Cohen, David, Sharma, Satish, Liangpunsakul, Suthat, Oursler, Kris Ann, Whooley, Mary, Ahuja, Sunil, Constans, Joseph, Meyer, Paul, Greco, Jennifer, Rauchman, Michael, Servatius, Richard, Gaddy, Melinda, Wallbom, Agnes, Morgan, Timothy, Stapley, Todd, Sherman, Scott, Ross, George, Tsao, Philip, Strollo, Patrick, Boyko, Edward, Meyer, Laurence, Gupta, Samir, Huq, Mostaqul, Fayad, Joseph, Hung, Adriana, Lichy, Jack, Hurley, Robin, Robey, Brooks, Striker, Robert, Wray, Naomi R., Mattheisen, Manuel, Trzaskowski, Maciej, Byrne, Enda M., Abdellaoui, Abdel, Adams, Mark J., Agerbo, Esben, Air, Tracy M., Andlauer, Till F. M., Bacanu, Silviu-Alin, Bækvad-Hansen, Marie, Beekman, Aartjan T. F., Bigdeli, Tim B., Binder, Elisabeth B., Bryois, Julien, Buttenschøn, Henriette N., Bybjerg-Grauholm, Jonas, Cai, Na, Castelao, Enrique, Christensen, Jane Hvarregaard, Clarke, Toni-Kim, Coleman, Jonathan R. I., Colodro-Conde, Lucía, Couvy-Duchesne, Baptiste, Craddock, Nick, Crawford, Gregory E., Davies, Gail, Degenhardt, Franziska, Derks, Eske M., Direk, Nese, Dolan, Conor V., Dunn, Erin C., Eley, Thalia C., Escott-Price, Valentina, Hassan Kiadeh, Farnush Farhadi, Finucane, Hilary K., Foo, Jerome C., Forstner, Andreas J., Frank, Josef, Gaspar, Héléna A., Gill, Michael, Goes, Fernando S., Gordon, Scott D., Weinsheimer, Shantel Marie, Wellmann, Jürgen, Willemsen, Gonneke, Witt, Stephanie H., Wu, Yang, Xi, Hualin S., Yang, Jian, Zhang, Futao, Arolt, Volker, Baune, Bernhard T., Berger, Klaus, Boomsma, Dorret I., Cichon, Sven, Dannlowski, Udo, de Geus, E. J. C., DePaulo, J. Raymond, Domenici, Enrico, Domschke, Katharina, Esko, Tõnu, Grabe, Hans J., Hamilton, Steven P., Grove, Jakob, Hall, Lynsey S., Hansen, Christine Søholm, Hansen, Thomas F., Herms, Stefan, Hickie, Ian B., Hoffmann, Per, Homuth, Georg, Horn, Carsten, Hottenga, Jouke-Jan, Hougaard, David M., Howard, David M., Ising, Marcus, Jansen, Rick, Jones, Ian, Jones, Lisa A., Jorgenson, Eric, Knowles, James A., Kohane, Isaac S., Kraft, Julia, Kretzschmar, Warren W., Kutalik, Zoltán, Li, Yihan, Lind, Penelope A., MacIntyre, Donald J., MacKinnon, Dean F., Maier, Robert M., Maier, Wolfgang, Marchini, Jonathan, Mbarek, Hamdi, McGrath, Patrick, McGuffin, Peter, Medland, Sarah E., Mehta, Divya, Middeldorp, Christel M., Mihailov, Evelin, Milaneschi, Yuri, Milani, Lili, Mondimore, Francis M., Montgomery, Grant W., Mostafavi, Sara, Mullins, Niamh, Nauck, Matthias, Ng, Bernard, Nivard, Michel G., Nyholt, Dale R., O'Reilly, Paul F., Oskarsson, Hogni, Hayward, Caroline, Heath, Andrew C., Kendler, Kenneth S., Kloiber, Stefan, Lewis, Glyn, Li, Qingqin S., Lucae, Susanne, Madden, Pamela A. F., Magnusson, Patrik K., Martin, Nicholas G., McIntosh, Andrew M., Metspalu, Andres, Mors, Ole, Mortensen, Preben Bo, Müller-Myhsok, Bertram, Nordentoft, Merete, O'Donovan, Michael C., Paciga, Sara A., Pedersen, Nancy L., Owen, Michael J., Painter, Jodie N., Pedersen, Carsten Bøcker, Pedersen, Marianne Giørtz, Peterson, Roseann E., Peyrot, Wouter J., Pistis, Giorgio, Posthuma, Danielle, Quiroz, Jorge A., Qvist, Per, Rice, John P., Riley, Brien P., Rivera, Margarita, Mirza, Saira Saeed, Schoevers, Robert, Schulte, Eva C., Shen, Ling, Shi, Jianxin, Shyn, Stanley I., Sigurdsson, Engilbert, Sinnamon, Grant C. B., Smit, Johannes H., Smith, Daniel J., Stefansson, Hreinn, Steinberg, Stacy, Streit, Fabian, Strohmaier, Jana, Tansey, Katherine E., Teismann, Henning, Teumer, Alexander, Thompson, Wesley, Thomson, Pippa A., Thorgeirsson, Thorgeir E., Traylor, Matthew, Treutlein, Jens, Trubetskoy, Vassily, Uitterlinden, André G., Umbricht, Daniel, Van der Auwera, Sandra, van Hemert, Albert M., Viktorin, Alexander, Visscher, Peter M., Wang, Yunpeng, Webb, Bradley T., Penninx, Brenda W. J. 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F., Ehrlich, S., Escaramis, G., Espeseth, T., Estivill, X., Farmer, A., Favaro, A., Fischer, K., Floyd, J. A. B., Focker, M., Foretova, L., Forzan, M., Franklin, C. S., Gambaro, G., Giuranna, J., Giusti-Rodriquez, P., Gonidakis, F., Gordon, S., Mayora, M. G., Guillaume, S., Hanscombe, K. B., Hatzikotoulas, K., Hebebrand, J., Helder, S. G., Henders, A. K., Herpertz-Dahlmann, B., Herzog, W., Hinney, A., Horwood, L. J., Hubel, C., Petersen, L. V., Purves, K. L., Raevuori, A., Reichborn-Kjennerud, T., Ricca, V., Ripatti, S., Ritschel, F., Roberts, M., Rybakowski, F., Santonastaso, P., Scherag, A., Schmidt, U., Schork, N. J., Schosser, A., Seitz, J., Slachtova, L., Slagboom, P. E., Slof-Op 't Landt, M. C. T., Slopien, A., Soranzo, N., Sorbi, S., Southam, L., Steen, V. W., Huckins, L. M., Hudson, J. I., Imgart, H., Inoko, H., Janout, V., Jordan, J., Julia, A., Kalsi, G., Kaminska, D., Kaprio, J., Karhunen, L., Karwautz, A., Kas, M. J. H., Kennedy, M. A., Keski-Rahkonen, A., Kiezebrink, K., Kim, Y. -R., Kirk, K. M., Klareskog, L., Knudsen, G. P. S., Larsen, J. T., Le Hellard, S., Leppa, V. M., Lichtenstein, P., Lin, B. D., Lundervold, A., Luykx, J., Maj, M., Mannik, K., Marsal, S., Stuber, G. D., Szatkiewicz, J. P., Tachmazidou, I., Tenconi, E., Tortorella, A., Tozzi, F., Tsitsika, A., Tyszkiewicz-Nwafor, M., Tziouvas, K., van Elburg, A. A., van Furth, E. F., Wade, T. D., Wagner, G., Walton, E., Whiteman, D. C., Wichmann, H. E., Widen, E., Yao, S., Zeggini, E., Zerwas, S., Zipfel, S., Jungkunz, M., Dietl, L., Schwarze, C. E., Dahmen, N., Schott, B. H., Mobascher, A., Crivelli, S., Dennis, M. F., Harvey, P. D., Carter, B. W., Huffman, J. E., Jacobson, D., Madduri, R., Olsen, M. K., Pestian, J., Gaziano, J. M., Muralidhar, S., Ramoni, R., Beckham, J., Chang, K. -M., O'Donnell, C. J., Tsao, P. S., Breeling, J., Huang, G., Romero, J. P. C., Moser, J., Whitbourne, S. B., Brewer, J. V., Aslan, M., Connor, T., Argyres, D. 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Subjects: LD SCORE REGRESSION, Genome-wide association study, Suicide, Attempted, 3124 Neurology and psychiatry, 0302 clinical medicine, Risk Factors, Insomnia, Suicide attempt, GWAS, Suïcidi, Depression (differential diagnoses), Cause of death, Psychiatry, 0303 health sciences, Factors de risc en les malalties, Mental Disorders, Genetic Correlation, Genome-wide Association Study, Pleiotropy, Polygenicity, Suicide, Suicide Attempt, DEPRESSION, 3. Good health, Genetic correlation, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Depressive Disorder, Major, Mental illness, Cohort, SEX, medicine.symptom, Human, medicine.medical_specialty, Risk factors in diseases, BF, Locus (genetics), BEHAVIORS, Psykiatri, EVENTS, 03 medical and health sciences, SDG 3 - Good Health and Well-being, medicine, ddc:610, GENOME-WIDE ASSOCIATION, IDEATION, Socioeconomic status, METAANALYSIS, Biological Psychiatry, 030304 developmental biology, business.industry, Risk Factor, Genetic architecture, THOUGHTS, RC0321, business, Malalties mentals, 030217 neurology & neurosurgery
Abstract: Statistical analyses were carried out on the NL Genetic Cluster Computer (http://www.geneticcluster.org) hosted by SURFsara and the Mount Sinai high performance computing cluster (http://hpc.mssm.edu), which is supported by the Office of Research Infrastructure of the National Institutes of Health (Grant Nos. S10OD018522 and S10OD026880). This work was conducted in part using the resources of the Advanced Computing Center for Research and Education at Vanderbilt University, Nashville, TN. This work was funded by the National Institutes of Health (Grant Nos. R01MH116269 and R01MH121455 [to DMR]), NIGMS of the National Institutes of Health (Grant No. T32GM007347 [to JK]), and the Brain & Behavior Research Foundation (NARSAD Young Investigator Award No. 29551 [to NM])., BACKGROUND: Suicide is a leading cause of death worldwide, and nonfatal suicide attempts, which occur far more frequently, are a major source of disability and social and economic burden. Both have substantial genetic etiology, which is partially shared and partially distinct from that of related psychiatric disorders. METHODS: We conducted a genome-wide association study (GWAS) of 29,782 suicide attempt (SA) cases and 519,961 controls in the International Suicide Genetics Consortium (ISGC). The GWAS of SA was conditioned on psychiatric disorders using GWAS summary statistics via multitrait-based conditional and joint analysis, to remove genetic effects on SA mediated by psychiatric disorders. We investigated the shared and divergent genetic architectures of SA, psychiatric disorders, and other known risk factors. RESULTS: Two loci reached genome-wide significance for SA: the major histocompatibility complex and an intergenic locus on chromosome 7, the latter of which remained associated with SA after conditioning on psychiatric disorders and replicated in an independent cohort from the Million Veteran Program. This locus has been implicated in risk-taking behavior, smoking, and insomnia. SA showed strong genetic correlation with psychiatric disorders, particularly major depression, and also with smoking, pain, risk-taking behavior, sleep disturbances, lower educational attainment, reproductive traits, lower socioeconomic status, and poorer general health. After conditioning on psychiatric disorders, the genetic correlations between SA and psychiatric disorders decreased, whereas those with nonpsychiatric traits remained largely unchanged. CONCLUSIONS: Our results identify a risk locus that contributes more strongly to SA than other phenotypes and suggest a shared underlying biology between SA and known risk factors that is not mediated by psychiatric disorders., Office of Research Infrastructure of the National Institutes of Health S10OD018522 S10OD026880, United States Department of Health & Human Services, National Institutes of Health (NIH) - USA R01MH116269 R01MH121455, NIH National Institute of General Medical Sciences (NIGMS) T32GM007347 NARSAD 29551
Published: 2022

17. The power of genetic diversity in genome-wide association studies of lipids

Author: Graham, Sarah E, Clarke, Shoa L, Wu, Kuan-Han H, Kanoni, Stavroula, Zajac, Greg JM, Ramdas, Shweta, Surakka, Ida, Ntalla, Ioanna, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Hwang, Mi Yeong, Han, Sohee, Narita, Akira, Choudhury, Ananyo, Bentley, Amy R, Ekoru, Kenneth, Verma, Anurag, Trivedi, Bhavi, Martin, Hilary C, Hunt, Karen A, Hui, Qin, Klarin, Derek, Zhu, Xiang, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Ruotsalainen, Sanni E, Havulinna, Aki S, Veturi, Yogasudha, Feng, QiPing, Rosenthal, Elisabeth A, Lingren, Todd, Pacheco, Jennifer Allen, Pendergrass, Sarah A, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Hindy, George, Rasheed, Asif, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Mahajan, Anubha, Brown, Michael R, Zhang, Weihua, Yu, Ketian, Schmidt, Ellen M, Pandit, Anita, Gustafsson, Stefan, Yin, Xianyong, Luan, Jian’an, Zhao, Jing-Hua, Matsuda, Fumihiko, Jang, Hye-Mi, Yoon, Kyungheon, Medina-Gomez, Carolina, Pitsillides, Achilleas, Hottenga, Jouke Jan, Willemsen, Gonneke, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Yao, Jie, Manichaikul, Ani, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Sidore, Carlo, Fiorillo, Edoardo, McDaid, Aaron F, Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T, Thuesen, Betina H, Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Daw, E Warwick, Zmuda, Joseph M, Mitchell, Jonathan S, Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A, Feitosa, Mary F, Wojczynski, Mary K, Preuss, Michael, Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W, Engmann, Jorgen, Kember, Rachel L, Slieker, Roderick C, Lo, Ken Sin, Zilhao, Nuno R, Le, Phuong, Kleber, Marcus E, Delgado, Graciela E, Huo, Shaofeng, Ikeda, Daisuke D, Iha, Hiroyuki, Yang, Jian, Liu, Jun, Leonard, Hampton L, Marten, Jonathan, Schmidt, Börge, Arendt, Marina, Smyth, Laura J, Cañadas-Garre, Marisa, Wang, Chaolong, Nakatochi, Masahiro, Wong, Andrew, Hutri-Kähönen, Nina, Sim, Xueling, Xia, Rui, Huerta-Chagoya, Alicia, Fernandez-Lopez, Juan Carlos, Lyssenko, Valeriya, Ahmed, Meraj, Jackson, Anne U, Irvin, Marguerite R, Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul RHJ, Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A, Chai, Xiaoran, Prasad, Gauri, Lorés-Motta, Laura, Pauper, Marc, Long, Jirong, Li, Xiaohui, Theusch, Elizabeth, Takeuchi, Fumihiko, Spracklen, Cassandra N, Loukola, Anu, Bollepalli, Sailalitha, Warner, Sophie C, Wang, Ya Xing, Wei, Wen B., Nutile, Teresa, Ruggiero, Daniela, Sung, Yun Ju, Hung, Yi-Jen, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A, Gorski, Mathias, Brumat, Marco, Meidtner, Karina, Bielak, Lawrence F, Smith, Jennifer A, Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Xue, Chao, Zhang, Jifeng, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J, Pitkänen, Niina, Cade, Brian E, Lee, Jiwon, van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Zimmermann, Martina E, Lee, Jong Young, Choi, Hyeok Sun, Nethander, Maria, Freitag-Wolf, Sandra, Southam, Lorraine, Rayner, Nigel W, Wang, Carol A, Lin, Shih-Yi, Wang, Jun-Sing, Couture, Christian, Lyytikäinen, Leo-Pekka, Nikus, Kjell, Cuellar-Partida, Gabriel, Vestergaard, Henrik, Hildalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O, van Setten, Jessica, Li, Xiaoyin, Schwander, Karen, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D, Reiner, Alexander P, Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Highland, Heather M, Young, Kristin L, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C, Nadkarni, Girish N., Launer, Lenore J, Li, Huaixing, Nalls, Mike A, Raitakari, Olli T, Ichihara, Sahoko, Wild, Sarah H, Nelson, Christopher P, Campbell, Harry, Jäger, Susanne, Nabika, Toru, Al-Mulla, Fahd, Niinikoski, Harri, Braund, Peter S, Kolcic, Ivana, Kovacs, Peter, Giardoglou, Tota, Katsuya, Tomohiro, Bhatti, Konain Fatima, de Kleijn, Dominique, de Borst, Gert J., Kim, Eung Kweon, Adams, Hieab H.H., Ikram, M. Arfan, Zhu, Xiaofeng, Asselbergs, Folkert W, Kraaijeveld, Adriaan O, Beulens, Joline WJ, Shu, Xiao-Ou, Rallidis, Loukianos S, Pedersen, Oluf, Hansen, Torben, Mitchell, Paul, Hewitt, Alex W, Kähönen, Mika, Pérusse, Louis, Bouchard, Claude, Tönjes, Anke, Chen, Yii-Der Ida, Pennell, Craig E, Mori, Trevor A, Lieb, Wolfgang, Franke, Andre, Ohlsson, Claes, Mellström, Dan, Cho, Yoon Shin, Lee, Hyejin, Yuan, Jian-Min, Koh, Woon-Puay, Rhee, Sang Youl, Woo, Jeong-Taek, Heid, Iris M, Stark, Klaus J, Völzke, Henry, Homuth, Georg, Evans, Michele K, Zonderman, Alan B, Polasek, Ozren, Pasterkamp, Gerard, Hoefer, Imo E, Redline, Susan, Pahkala, Katja, Oldehinkel, Albertine J, Snieder, Harold, Biino, Ginevra, Schmidt, Reinhold, Schmidt, Helena, Chen, Y Eugene, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon LR, Kato, Norihiro, Schulze, Matthias B, Girotto, Giorgia, Jung, Bettina, Böger, Carsten A, Joshi, Peter K, Bennett, David A, De Jager, Philip L, Lu, Xiangfeng, Mamakou, Vasiliki, Brown, Morris, Caulfield, Mark J, Munroe, Patricia B, Guo, Xiuqing, Ciullo, Marina, Jonas, Jost B., Samani, Nilesh J, Chasman, Daniel I., Kaprio, Jaakko, Pajukanta, Päivi, Tusié-Luna, Teresa, Aguilar-Salinas, Carlos A, Adair, Linda S, Bechayda, Sonny Augustin, de Silva, H. Janaka, Wickremasinghe, Ananda R, Krauss, Ronald M, Wu, Jer-Yuarn, Zheng, Wei, den Hollander, Anneke I, Bharadwaj, Dwaipayan, Correa, Adolfo, Wilson, James G, Lind, Lars, Heng, Chew-Kiat, Nelson, Amanda E, Golightly, Yvonne M, Wilson, James F, Penninx, Brenda, Kim, Hyung-Lae, Attia, John, Scott, Rodney J, Rao, D C, Arnett, Donna K, Walker, Mark, Koistinen, Heikki A, Chandak, Giriraj R, Yajnik, Chittaranjan S, Mercader, Josep M, Tusie-Luna, Teresa, Aguilar-Salinas, Carlos, Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, E Shyong, van Dam, Rob M, Lehtimäki, Terho, Chaturvedi, Nish, Yokota, Mitsuhiro, Liu, Jianjun, Reilly, Dermot F, McKnight, Amy Jayne, Kee, Frank, Jöckel, Karl-Heinz, McCarthy, Mark I, Palmer, Colin NA, Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M, Lu, Fan, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Parra, Esteban J, Cruz, Miguel, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M t, Elders, Petra JM, Rader, Daniel J, Damrauer, Scott M, Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D, Loos, Ruth J.F., Province, Michael A, Psaty, Bruce M, Brandslund, Ivan, Pramstaller, Peter P, Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F.A., Kiemeney, Lambertus ALM, de Graaf, Jacqueline, Loeffler, Markus, Kronenberg, Florian, Gu, Dongfeng, Erdmann, Jeanette, Schunkert, Heribert, Franks, Paul W, Linneberg, Allan, Jukema, J. Wouter, Khera, Amit V, Männikkö, Minna, Jarvelin, Marjo-Riitta, Kutalik, Zoltan, Cucca, Francesco, Mook-Kanamori, Dennis O, van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P, Grarup, Niels, Sever, Peter, Poulter, Neil, Rotter, Jerome I, Dantoft, Thomas M, Karpe, Fredrik, Neville, Matt J, Timpson, Nicholas J, Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T, Pedersen, Nancy L, Magnusson, Patrik KE, Boomsma, Dorret I, de Geus, Eco JC, Cupples, L Adrienne, van Meurs, Joyce B.J., Ghanbari, Mohsen, Gordon-Larsen, Penny, Huang, Wei, Kim, Young Jin, Tabara, Yasuharu, Wareham, Nicholas J, Langenberg, Claudia, Zeggini, Eleftheria, Kuusisto, Johanna, Laakso, Markku, Ingelsson, Erik, Abecasis, Goncalo, Chambers, John C, Kooner, Jaspal S, de Vries, Paul S, Morrison, Alanna C, North, Kari E., Daviglus, Martha, Kraft, Peter, Martin, Nicholas G, Whitfield, John B, Abbas, Shahid, Saleheen, Danish, Walters, Robin G, Holmes, Michael V, Black, Corri, Smith, Blair H, Justice, Anne E, Baras, Aris, Buring, Julie E, Ridker, Paul M, Chasman, Daniel I, Kooperberg, Charles, Wei, Wei-Qi, Jarvik, Gail P, Namjou, Bahram, Hayes, M. Geoffrey, Ritchie, Marylyn D, Jousilahti, Pekka, Salomaa, Veikko, Hveem, Kristian, Åsvold, Bjørn Olav, Kubo, Michiaki, Kamatani, Yoichiro, Okada, Yukinori, Murakami, Yoshinori, Thorsteinsdottir, Unnur, Stefansson, Kari, Ho, Yuk-Lam, Lynch, Julie A, Rader, Daniel, Tsao, Phil S, Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J, Gaziano, John M, Wilson, Peter, Rotimi, Charles N, Hazelhurst, Scott, Ramsay, Michèle, Trembath, Richard C, van Heel, David A, Tamiya, Gen, Yamamoto, Masayuki, Kim, Bong-Jo, Mohlke, Karen L, Frayling, Timothy M, Hirschhorn, Joel N, Kathiresan, Sekar, Boehnke, Michael, Natarajan, Pradeep, Peloso, Gina M, Brown, Christopher D, Morris, Andrew P, Assimes, Themistocles L, Deloukas, Panos, Sun, Yan V, Willer, Cristen J, VA Million Veteran Program, Global Lipids Genetics Consortium, Internal Medicine, Epidemiology, Radiology & Nuclear Medicine, Graham, S. E., Clarke, S. L., Wu, K. -H. H., Kanoni, S., Zajac, G. J. M., Ramdas, S., Surakka, I., Ntalla, I., Vedantam, S., Winkler, T. W., Locke, A. E., Marouli, E., Hwang, M. Y., Han, S., Narita, A., Choudhury, A., Bentley, A. R., Ekoru, K., Verma, A., Trivedi, B., Martin, H. C., Hunt, K. A., Hui, Q., Klarin, D., Zhu, X., Thorleifsson, G., Helgadottir, A., Gudbjartsson, D. F., Holm, H., Olafsson, I., Akiyama, M., Sakaue, S., Terao, C., Kanai, M., Zhou, W., Brumpton, B. M., Rasheed, H., Ruotsalainen, S. E., Havulinna, A. S., Veturi, Y., Feng, Q. P., Rosenthal, E. A., Lingren, T., Pacheco, J. A., Pendergrass, S. A., Haessler, J., Giulianini, F., Bradford, Y., Miller, J. E., Campbell, A., Lin, K., Millwood, I. Y., Hindy, G., Rasheed, A., Faul, J. D., Zhao, W., Weir, D. R., Turman, C., Huang, H., Graff, M., Mahajan, A., Brown, M. R., Zhang, W., Yu, K., Schmidt, E. M., Pandit, A., Gustafsson, S., Yin, X., Luan, J., Zhao, J. -H., Matsuda, F., Jang, H. -M., Yoon, K., Medina-Gomez, C., Pitsillides, A., Hottenga, J. J., Willemsen, G., Wood, A. R., Ji, Y., Gao, Z., Haworth, S., Mitchell, R. E., Chai, J. F., Aadahl, M., Yao, J., Manichaikul, A., Warren, H. R., Ramirez, J., Bork-Jensen, J., Karhus, L. L., Goel, A., Sabater-Lleal, M., Noordam, R., Sidore, C., Fiorillo, E., Mcdaid, A. F., Marques-Vidal, P., Wielscher, M., Trompet, S., Sattar, N., Mollehave, L. T., Thuesen, B. H., Munz, M., Zeng, L., Huang, J., Yang, B., Poveda, A., Kurbasic, A., Lamina, C., Forer, L., Scholz, M., Galesloot, T. E., Bradfield, J. P., Daw, E. W., Zmuda, J. M., Mitchell, J. S., Fuchsberger, C., Christensen, H., Brody, J. A., Feitosa, M. F., Wojczynski, M. K., Preuss, M., Mangino, M., Christofidou, P., Verweij, N., Benjamins, J. W., Engmann, J., Kember, R. L., Slieker, R. C., Lo, K. S., Zilhao, N. R., Le, P., Kleber, M. E., Delgado, G. E., Huo, S., Ikeda, D. D., Iha, H., Yang, J., Liu, J., Leonard, H. L., Marten, J., Schmidt, B., Arendt, M., Smyth, L. J., Canadas-Garre, M., Wang, C., Nakatochi, M., Wong, A., Hutri-Kahonen, N., Sim, X., Xia, R., Huerta-Chagoya, A., Fernandez-Lopez, J. C., Lyssenko, V., Ahmed, M., Jackson, A. U., Irvin, M. R., Oldmeadow, C., Kim, H. -N., Ryu, S., Timmers, P. R. H. J., Arbeeva, L., Dorajoo, R., Lange, L. A., Chai, X., Prasad, G., Lores-Motta, L., Pauper, M., Long, J., Li, X., Theusch, E., Takeuchi, F., Spracklen, C. N., Loukola, A., Bollepalli, S., Warner, S. C., Wang, Y. X., Wei, W. B., Nutile, T., Ruggiero, D., Sung, Y. J., Hung, Y. -J., Chen, S., Liu, F., Kentistou, K. A., Gorski, M., Brumat, M., Meidtner, K., Bielak, L. F., Smith, J. A., Hebbar, P., Farmaki, A. -E., Hofer, E., Lin, M., Xue, C., Zhang, J., Concas, M. P., Vaccargiu, S., van der Most, P. J., Pitkanen, N., Cade, B. E., Lee, J., van der Laan, S. W., Chitrala, K. N., Weiss, S., Zimmermann, M. E., Lee, J. Y., Choi, H. S., Nethander, M., Freitag-Wolf, S., Southam, L., Rayner, N. W., Wang, C. A., Lin, S. -Y., Wang, J. -S., Couture, C., Lyytikainen, L. -P., Nikus, K., Cuellar-Partida, G., Vestergaard, H., Hildalgo, B., Giannakopoulou, O., Cai, Q., Obura, M. O., van Setten, J., Schwander, K., Terzikhan, N., Shin, J. H., Jackson, R. D., Reiner, A. P., Martin, L. W., Chen, Z., Li, L., Highland, H. M., Young, K. L., Kawaguchi, T., Thiery, J., Bis, J. C., Nadkarni, G. N., Launer, L. J., Li, H., Nalls, M. A., Raitakari, O. T., Ichihara, S., Wild, S. H., Nelson, C. P., Campbell, H., Jager, S., Nabika, T., Al-Mulla, F., Niinikoski, H., Braund, P. S., Kolcic, I., Kovacs, P., Giardoglou, T., Katsuya, T., Bhatti, K. F., de Kleijn, D., de Borst, G. J., Kim, E. K., Adams, H. H. H., Ikram, M. A., Asselbergs, F. W., Kraaijeveld, A. O., Beulens, J. W. J., Shu, X. -O., Rallidis, L. S., Pedersen, O., Hansen, T., Mitchell, P., Hewitt, A. W., Kahonen, M., Perusse, L., Bouchard, C., Tonjes, A., Chen, Y. -D. I., Pennell, C. E., Mori, T. A., Lieb, W., Franke, A., Ohlsson, C., Mellstrom, D., Cho, Y. S., Lee, H., Yuan, J. -M., Koh, W. -P., Rhee, S. Y., Woo, J. -T., Heid, I. M., Stark, K. J., Volzke, H., Homuth, G., Evans, M. K., Zonderman, A. B., Polasek, O., Pasterkamp, G., Hoefer, I. E., Redline, S., Pahkala, K., Oldehinkel, A. J., Snieder, H., Biino, G., Schmidt, R., Schmidt, H., Chen, Y. E., Bandinelli, S., Dedoussis, G., Thanaraj, T. A., Kardia, S. L. R., Kato, N., Schulze, M. B., Girotto, G., Jung, B., Boger, C. A., Joshi, P. K., Bennett, D. A., De Jager, P. L., Lu, X., Mamakou, V., Brown, M., Caulfield, M. J., Munroe, P. B., Guo, X., Ciullo, M., Jonas, J. B., Samani, N. J., Kaprio, J., Pajukanta, P., Adair, L. S., Bechayda, S. A., de Silva, H. J., Wickremasinghe, A. R., Krauss, R. M., Wu, J. -Y., Zheng, W., den Hollander, A. I., Bharadwaj, D., Correa, A., Wilson, J. G., Lind, L., Heng, C. -K., Nelson, A. E., Golightly, Y. M., Wilson, J. F., Penninx, B., Kim, H. -L., Attia, J., Scott, R. J., Rao, D. C., Arnett, D. K., Walker, M., Koistinen, H. A., Chandak, G. R., Yajnik, C. S., Mercader, J. M., Tusie-Luna, T., Aguilar-Salinas, C. A., Villalpando, C. G., Orozco, L., Fornage, M., Tai, E. S., van Dam, R. M., Lehtimaki, T., Chaturvedi, N., Yokota, M., Reilly, D. F., Mcknight, A. J., Kee, F., Jockel, K. -H., Mccarthy, M. I., Palmer, C. N. A., Vitart, V., Hayward, C., Simonsick, E., van Duijn, C. M., Lu, F., Qu, J., Hishigaki, H., Lin, X., Marz, W., Parra, E. J., Cruz, M., Gudnason, V., Tardif, J. -C., Lettre, G., 't Hart, L. M., Elders, P. J. M., Damrauer, S. M., Kumari, M., Kivimaki, M., van der Harst, P., Spector, T. D., Loos, R. J. F., Province, M. A., Psaty, B. M., Brandslund, I., Pramstaller, P. P., Christensen, K., Ripatti, S., Widen, E., Hakonarson, H., Grant, S. F. A., Kiemeney, L. A. L. M., de Graaf, J., Loeffler, M., Kronenberg, F., Gu, D., Erdmann, J., Schunkert, H., Franks, P. W., Linneberg, A., Jukema, J. W., Khera, A. V., Mannikko, M., Jarvelin, M. -R., Kutalik, Z., Cucca, F., Mook-Kanamori, D. O., van Dijk, K. W., Watkins, H., Strachan, D. P., Grarup, N., Sever, P., Poulter, N., Rotter, J. I., Dantoft, T. M., Karpe, F., Neville, M. J., Timpson, N. J., Cheng, C. -Y., Wong, T. -Y., Khor, C. C., Sabanayagam, C., Peters, A., Gieger, C., Hattersley, A. T., Pedersen, N. L., Magnusson, P. K. E., Boomsma, D. I., de Geus, E. J. C., Cupples, L. A., van Meurs, J. B. J., Ghanbari, M., Gordon-Larsen, P., Huang, W., Kim, Y. J., Tabara, Y., Wareham, N. J., Langenberg, C., Zeggini, E., Kuusisto, J., Laakso, M., Ingelsson, E., Abecasis, G., Chambers, J. C., Kooner, J. S., de Vries, P. S., Morrison, A. C., North, K. E., Daviglus, M., Kraft, P., Martin, N. G., Whitfield, J. B., Abbas, S., Saleheen, D., Walters, R. G., Holmes, M. V., Black, C., Smith, B. H., Justice, A. E., Baras, A., Buring, J. E., Ridker, P. M., Chasman, D. I., Kooperberg, C., Wei, W. -Q., Jarvik, G. P., Namjou, B., Hayes, M. G., Ritchie, M. D., Jousilahti, P., Salomaa, V., Hveem, K., Asvold, B. O., Kubo, M., Kamatani, Y., Okada, Y., Murakami, Y., Thorsteinsdottir, U., Stefansson, K., Ho, Y. -L., Lynch, J. A., Rader, D. J., Tsao, P. S., Chang, K. -M., Cho, K., O'Donnell, C. J., Gaziano, J. M., Wilson, P., Rotimi, C. N., Hazelhurst, S., Ramsay, M., Trembath, R. C., van Heel, D. A., Tamiya, G., Yamamoto, M., Kim, B. -J., Mohlke, K. L., Frayling, T. M., Hirschhorn, J. N., Kathiresan, S., Boehnke, M., Natarajan, P., Peloso, G. M., Brown, C. D., Morris, A. P., Assimes, T. L., Deloukas, P., Sun, Y. V., Willer, C. J., Interdisciplinary Centre Psychopathology and Emotion regulation (ICPE), Life Course Epidemiology (LCE), Cardiovascular Centre (CVC), Biological Psychology, APH - Health Behaviors & Chronic Diseases, APH - Personalized Medicine, APH - Mental Health, APH - Methodology, AMS - Ageing & Vitality, and AMS - Sports
Subjects: blood lipid level, Multifactorial Inheritance, GWAS, blood lipid levels, cardiovascular disease, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], Medizin, LOCI, ANCESTRY, VARIANTS, Polymorphism, Single Nucleotide, Linkage Disequilibrium, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], Article, Population Groups, SDG 3 - Good Health and Well-being, Humans, Genetic Predisposition to Disease, METAANALYSIS, POLYMORPHISMS, RISK, Multidisciplinary, Cardiovascular Diseases, Genome-Wide Association Study, Cardiovascular Diseases/genetics, Genetic Predisposition to Disease/genetics, Genome-Wide Association Study/methods, Polymorphism, Single Nucleotide/genetics, CHOLESTEROL, Human Genetics, INDIVIDUALS, Urological cancers Radboud Institute for Health Sciences [Radboudumc 15], DISCOVERY, LOW-FREQUENCY, Delivery of Health Care
Abstract: Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use 1 . Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels 2 , heart disease remains the leading cause of death worldwide 3 . Genome-wideassociation studies (GWAS) of blood lipid levels have led to important biological and clinical insights, as well as new drug targets, for cardiovascular disease. However, most previous GWAS 4-23 have been conducted in European ancestry populations and may have missed genetic variants that contribute to lipid-level variation in other ancestry groups. These include differences in allele frequencies, effect sizes and linkage-disequilibrium patterns 24 . Here we conduct a multi-ancestry, genome-wide genetic discovery meta-analysis of lipid levels in approximately 1.65 million individuals, including 350,000 of non-European ancestries. We quantify the gain in studying non-European ancestries and provide evidence to support the expansion of recruitment of additional ancestries, even with relatively small sample sizes. We find that increasing diversity rather than studying additional individuals of European ancestry results in substantial improvements in fine-mapping functional variants and portability of polygenic prediction (evaluated in approximately 295,000 individuals from 7 ancestry groupings). Modest gains in the number of discovered loci and ancestry-specific variants were also achieved. As GWAS expand emphasis beyond the identification of genes and fundamental biology towards the use of genetic variants for preventive and precision medicine 25 , we anticipate that increased diversity of participants will lead to more accurate and equitable 26 application of polygenic scores in clinical practice.
Published: 2021

18. A0590 - Trans-ethnic genome-wide association study reveals new therapeutic targets for benign prostatic hyperplasia.

Author: Ng, M., Matsuda, K., Tanikawa, C., Terao, C., Kamatani, Y., Wei, W., Auton, A., Turney, B.W., Bryant, R.J., and Furniss, D.
Subjects: *BENIGN prostatic hyperplasia, *GENOME-wide association studies, *DRUG target
Published: 2022
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19. Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

Author: Akiyama M, Tamiya G, Fujiwara K, Shiga Y, Yokoyama Y, Hashimoto K, Sato M, Sato K, Narita A, Hashimoto S, Ueda E, Furuta Y, Hata J, Miyake M, Ikeda HO, Suda K, Numa S, Mori Y, Morino K, Murakami Y, Shimokawa S, Nakamura S, Yawata N, Fujisawa K, Yamana S, Mori K, Ikeda Y, Miyata K, Mori K, Ogino K, Koyanagi Y, Kamatani Y, Ninomiya T, Sonoda KH, and Nakazawa T
Subjects: Aged, Female, Humans, Male, Middle Aged, Cross-Sectional Studies, East Asian People genetics, Genome-Wide Association Study, Japan epidemiology, Polymorphism, Single Nucleotide, Risk Assessment methods, Risk Factors, ROC Curve, Visual Fields physiology, Genetic Predisposition to Disease, Glaucoma, Open-Angle genetics, Glaucoma, Open-Angle diagnosis, Intraocular Pressure physiology
Abstract: Purpose: To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals., Design: Cross-sectional analysis., Participants: Genetic risk scores (GRSs) were constructed based on a genome-wide association study (GWAS) of POAG in Japanese people. A total of 3625 Japanese individuals, including 1191 patients and 2434 controls (Japanese Tohoku), were used for the model selection. We also evaluated the discriminative accuracy of constructed GRSs in a dataset comprising 1034 patients and 1147 controls (the Japan Glaucoma Society Omics Group [JGS-OG] and the Genomic Research Committee of the Japanese Ophthalmological Society [GRC-JOS]) and 1900 participants from a population-based study (Hisayama Study)., Methods: We evaluated 2 types of GRSs: polygenic risk scores using the pruning and thresholding procedure and a GRS using variants associated with POAG in the GWAS of the International Glaucoma Genetics Consortium (IGGC). We selected the model with the highest areas under the receiver operating characteristic curve (AUC). In the population-based study, we evaluated the correlations between GRS and ocular measurements., Main Outcome Measure: Proportion of patients with POAG after stratification according to the GRS., Results: We found that a GRS using 98 variants, which showed genome-wide significance in the IGGC, showed the best discriminative accuracy (AUC, 0.65). In the Japanese Tohoku, the proportion of patients with POAG in the top 10% individuals was significantly higher than that in the lowest 10% (odds ratio [OR], 6.15; 95% confidence interval [CI], 4.35-8.71). In the JGS-OG and GRC-JOS, we confirmed similar impact of POAG GRS (AUC, 0.64; OR [top vs. bottom decile], 5.81; 95% CI, 3.79-9.01). In the population-based study, POAG prevalence was significantly higher in the top 20% individuals of the GRS compared with the bottom 20% (9.2% vs. 5.0%). However, the discriminative accuracy was low (AUC, 0.56). The POAG GRS was correlated positively with intraocular pressure (r = 0.08: P = 4.0 × 10 -4 ) and vertical cup-to-disc ratio (r = 0.11; P = 4.0 × 10 -6 )., Conclusions: The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance., Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article., (Copyright © 2024 American Academy of Ophthalmology. Published by Elsevier Inc. All rights reserved.)
Published: 2024
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20. Genomic variants associated with age at diagnosis of childhood-onset type 1 diabetes.

Author: Bougnères P, Le Fur S, Kamatani Y, Mai TN, Belot MP, Perge K, Shao X, Lathrop M, and Valleron AJ
Subjects: Humans, Child, Male, Female, Adolescent, Child, Preschool, Genotype, Genome-Wide Association Study, Infant, Diabetes Mellitus, Type 1 genetics, Diabetes Mellitus, Type 1 diagnosis, Diabetes Mellitus, Type 1 epidemiology, Polymorphism, Single Nucleotide, Age of Onset, Genetic Predisposition to Disease
Abstract: Age at diagnosis (AAD) of Type 1 diabetes (T1D) is determined by the age at onset of the autoimmune attack and by the rate of beta cell destruction that follows. Twin studies found that T1D AAD is strongly influenced by genetics, notably in young children. In young UK, Finnish, Sardinian patients AAD-associated genomic variants were previously identified, which may vary across populations and with time. In 1956 children of European ancestry born in mainland France in 1980-2008 who declared T1D before 15 years, we tested 94 T1D-associated SNPs for their association with AAD using nonparametric Kruskal-Wallis test. While high-risk HLA genotypes were not found to be associated with AAD, fourteen SNPs located in 12 non-HLA loci showed a strong association (2.9 × 10 -12 < P < 1.4 × 10 -3 after FDR correction). Four of these loci have been associated with AAD in previous cohorts (GSDMB, IL2, TNFAIP3, IL1), supporting a partially shared genetic influence on AAD of T1D in the studied European populations. In contrast, the association of 8 new loci CLEC16A, TYK2, ERBB3, CCR7, FCRL3, DNAH2, FGF3/4, and HPSE2 with AAD is novel. The 12 protein-coding genes located within these loci are involved in major immune pathways or in predisposition to other autoimmune diseases, which suggests a prominent role for these genes in the early immune mechanisms of beta cell destruction., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
Published: 2024
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21. Identification of epistatic SNP combinations in rheumatoid arthritis using LAMPLINK and Japanese cohorts.

Author: Shibata M, Terada A, Kawaguchi T, Kamatani Y, Okada D, Nagashima K, Ohmura K, Matsuda F, Kawaguchi S, Sese J, and Yamada R
Subjects: Female, Humans, Male, Middle Aged, Cohort Studies, East Asian People genetics, Haplotypes, Japan epidemiology, Arthritis, Rheumatoid genetics, Epistasis, Genetic, Genetic Predisposition to Disease, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Abstract: Genome-wide association studies have enabled the identification of important genetic factors in many trait studies. However, only a fraction of the heritability can be explained by known genetic factors, even in the most common diseases. Genetic loci combinations, or epistatic contributions expressed by combinations of single nucleotide polymorphisms (SNPs), have been argued to be one of the critical factors explaining some of the missing heritability, especially in oligogenic/polygenic diseases. Rheumatoid arthritis (RA) is a complex disease with more than 100 reported SNP associations, as well as various HLA haplotypes and amino acids; however, many associations between RA and inter-chromosomal SNP combinations are unknown. To discover novel associations of epistatic interactions with high odds ratios in RA, we applied the LAMPLINK method, a systematic enumerative procedure for identifying high-order SNP combinations, to a Japanese RA cohort (discovery cohort; 4024 patients with RA and 7731 controls). We validated the identified associations in a different Japanese cohort (validation cohort; 810 RA patients and 6303 controls). In this study, we identified 90 significant genetic associations in the discovery cohort. Among these, 74 (82.2%) associations were replicated in the validation cohort, and eight combinations were inter-chromosomal, all of which comprised rs7765379 or rs35265698 located in the HLA region. These two SNPs exhibited strong correlations with valine at amino acid position 11 in HLA-DRB1 (HLA-DRB1-11-Val). Finally, we discovered that rs9624 showed an association with RA through an epistatic interaction with HLA-DRB1-11-Val. Overall, LAMPLINK showed high reliability for identifying epistatic genetic contributions hidden in complex traits., (© 2024. The Author(s), under exclusive licence to The Japan Society of Human Genetics.)
Published: 2024
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22. Artificial intelligence in medical genomics.

Author: Kamatani Y and Kaname T
Subjects: Humans, Artificial Intelligence, Genomics methods
Published: 2024
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23. Increased somatic mosaicism in autosomal and X chromosomes for suicide death.

Author: Otsuka I, Uchiyama S, Shirai T, Liu X, Takahashi M, Kamatani Y, Terao C, and Hishimoto A
Abstract: Mosaic chromosomal alterations (mCAs) are classified as mosaic deletions (loss), copy-neutral loss of heterozygosity (CN-LOH), and duplications (gain), attracting special attention as biological aging-related acquired genetic alterations. While these mCAs have been linked with aging and various diseases, no study has investigated their association with suicide risk which is associated with abnormal biological aging. Here, we examined the association between suicide deaths and mCAs, including mosaic loss of the X (mLOX) and Y chromosomes, by leveraging blood-derived single nucleotide polymorphism-array data. The first (410 suicide decedents and 88,870 controls) and the second (363 suicide decedents and 88,870 controls) cohorts were analyzed and integrated using meta-analyses (773 suicide decedents and 177,740 controls). Total mCAs in autosomal chromosomes were significantly increased in suicide (p = 1.28 × 10 -6 , odds ratio [OR] = 1.78), mostly driven by loss (p = 4.05 × 10 -9 , OR = 2.70) and gain (p = 1.08 × 10 -3 , OR = 2.23). mLOX were significantly increased in female suicide (p = 2.66 × 10 -21 , OR = 4.00). The directions of effects of all mCAs in autosomal and sex chromosomes on suicide were the same in the first and second sets. Subgroup analyses suggest that our findings were mostly driven by suicide itself, and not confounded by comorbid psychiatric disorders or physical diseases, smoking status, sample location, or postmortem sample status. In conclusion, we provide the first evidence for aberrant mCAs in somatic autosomal and X chromosomes in suicide, which may contribute to an improved understanding of the genomic pathophysiology underlying suicide., (© 2024. The Author(s).)
Published: 2024
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24. Publisher Correction: Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Author: Kentistou KA, Kaisinger LR, Stankovic S, Vaudel M, Mendes de Oliveira E, Messina A, Walters RG, Liu X, Busch AS, Helgason H, Thompson DJ, Santoni F, Petricek KM, Zouaghi Y, Huang-Doran I, Gudbjartsson DF, Bratland E, Lin K, Gardner EJ, Zhao Y, Jia RY, Terao C, Riggan MJ, Bolla MK, Yazdanpanah M, Yazdanpanah N, Bradfield JP, Broer L, Campbell A, Chasman DI, Cousminer DL, Franceschini N, Franke LH, Girotto G, He C, Järvelin MR, Joshi PK, Kamatani Y, Karlsson R, Luan J, Lunetta KL, Mägi R, Mangino M, Medland SE, Meisinger C, Noordam R, Nutile T, Concas MP, Polašek O, Porcu E, Ring SM, Sala C, Smith AV, Tanaka T, van der Most PJ, Vitart V, Wang CA, Willemsen G, Zygmunt M, Ahearn TU, Andrulis IL, Anton-Culver H, Antoniou AC, Auer PL, Barnes CLK, Beckmann MW, Berrington de Gonzalez A, Bogdanova NV, Bojesen SE, Brenner H, Buring JE, Canzian F, Chang-Claude J, Couch FJ, Cox A, Crisponi L, Czene K, Daly MB, Demerath EW, Dennis J, Devilee P, De Vivo I, Dörk T, Dunning AM, Dwek M, Eriksson JG, Fasching PA, Fernandez-Rhodes L, Ferreli L, Fletcher O, Gago-Dominguez M, García-Closas M, García-Sáenz JA, González-Neira A, Grallert H, Guénel P, Haiman CA, Hall P, Hamann U, Hakonarson H, Hart RJ, Hickey M, Hooning MJ, Hoppe R, Hopper JL, Hottenga JJ, Hu FB, Huebner H, Hunter DJ, Jernström H, John EM, Karasik D, Khusnutdinova EK, Kristensen VN, Lacey JV, Lambrechts D, Launer LJ, Lind PA, Lindblom A, Magnusson PKE, Mannermaa A, McCarthy MI, Meitinger T, Menni C, Michailidou K, Millwood IY, Milne RL, Montgomery GW, Nevanlinna H, Nolte IM, Nyholt DR, Obi N, O'Brien KM, Offit K, Oldehinkel AJ, Ostrowski SR, Palotie A, Pedersen OB, Peters A, Pianigiani G, Plaseska-Karanfilska D, Pouta A, Pozarickij A, Radice P, Rennert G, Rosendaal FR, Ruggiero D, Saloustros E, Sandler DP, Schipf S, Schmidt CO, Schmidt MK, Small K, Spedicati B, Stampfer M, Stone J, Tamimi RM, Teras LR, Tikkanen E, Turman C, Vachon CM, Wang Q, Winqvist R, Wolk A, Zemel BS, Zheng W, van Dijk KW, Alizadeh BZ, Bandinelli S, Boerwinkle E, Boomsma DI, Ciullo M, Chenevix-Trench G, Cucca F, Esko T, Gieger C, Grant SFA, Gudnason V, Hayward C, Kolčić I, Kraft P, Lawlor DA, Martin NG, Nøhr EA, Pedersen NL, Pennell CE, Ridker PM, Robino A, Snieder H, Sovio U, Spector TD, Stöckl D, Sudlow C, Timpson NJ, Toniolo D, Uitterlinden A, Ulivi S, Völzke H, Wareham NJ, Widen E, Wilson JF, Pharoah PDP, Li L, Easton DF, Njølstad PR, Sulem P, Murabito JM, Murray A, Manousaki D, Juul A, Erikstrup C, Stefansson K, Horikoshi M, Chen Z, Farooqi IS, Pitteloud N, Johansson S, Day FR, Perry JRB, and Ong KK
Published: 2024
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25. RNF213 Variants, Vasospastic Angina, and Risk of Fatal Myocardial Infarction.

Author: Hikino K, Koyama S, Ito K, Koike Y, Koido M, Matsumura T, Kurosawa R, Tomizuka K, Ito S, Liu X, Ishikawa Y, Momozawa Y, Morisaki T, Kamatani Y, Mushiroda T, and Terao C
Subjects: Humans, Male, Female, Aged, Case-Control Studies, Middle Aged, Japan epidemiology, Coronary Vasospasm genetics, Genetic Predisposition to Disease, Angina Pectoris, Variant genetics, Risk Factors, Genome-Wide Association Study, Myocardial Infarction genetics, Myocardial Infarction epidemiology, Polymorphism, Single Nucleotide, Ubiquitin-Protein Ligases genetics, Adenosine Triphosphatases genetics
Abstract: Importance: Vasospastic angina (VSA) is vasospasm of the coronary artery and is particularly prevalent in East Asian populations. However, the specific genetic architecture for VSA at genome-wide levels is not fully understood., Objective: To identify genetic factors associated with VSA., Design, Setting, and Participants: This was a case-control genome-wide association study of VSA. Data from Biobank Japan (BBJ; enrolled patients from 2002-2008 and 2013-2018) were used, and controls without coronary artery disease (CAD) were enrolled. Patients from the BBJ were genotyped using arrays or a set of arrays. Patients recruited between 2002 and 2005 were classified within the first dataset, and those recruited between 2006 and 2008 were classified within the second dataset. To replicate the genome-wide association study in the first and second datasets, VSA cases and control samples from the latest patients in the BBJ recruited between 2013 and 2018 were analyzed in a third dataset., Exposures: Single-nucleotide variants associated with VSA., Main Outcomes and Measures: Cases with VSA and controls without CAD., Results: A total of 5720 cases (mean [SD] age, 67 [10] years; 3672 male [64.2%]) and 153 864 controls (mean [SD] age, 62 [15] years; 77 362 male [50.3%]) in 3 datasets were included in this study. The variants at the RNF213 locus showed the strongest association with VSA across the 3 datasets (odds ratio [OR], 2.34; 95% CI, 1.99-2.74; P = 4.4 × 10-25). Additionally, rs112735431, an Asian-specific rare deleterious variant (p.Arg4810Lys) experimentally shown to be associated with reduced angiogenesis and a well-known causal risk for Moyamoya disease was the most promising candidate for a causal variant explaining the association. The effect size of rs112735431 on VSA was distinct from that of other CADs. Furthermore, homozygous carriers of rs112735431 showed an association with VSA characterized by a large effect estimate (OR, 18.34; 95% CI, 5.15-65.22; P = 7.0 × 10-6), deviating from the additive model (OR, 4.35; 95% CI, 1.18-16.05; P = .03). Stratified analyses revealed that rs112735431 exhibited a stronger association in males (χ21 = 7.24; P = .007) and a younger age group (OR, 3.06; 95% CI, 2.24-4.19), corresponding to the epidemiologic features of VSA. In the registry, carriers without CAD of the risk allele rs112735431 had a strikingly high mortality rate due to acute myocardial infarction during the follow-up period (hazard ratio, 2.71; 95% CI, 1.57-4.65; P = 3.3 × 10-4). As previously reported, a possible overlap between VSA and Moyamoya disease was not found., Conclusions and Relevance: Results of this study suggest that vascular cell dysfunction mediated by variants in the RNF213 locus may promote coronary vasospasm, and the presence of the risk allele could serve as a predictive factor for the prognosis.
Published: 2024
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26. Causal relevance of different blood pressure traits on risk of cardiovascular diseases: GWAS and Mendelian randomisation in 100,000 Chinese adults.

Author: Pozarickij A, Gan W, Lin K, Clarke R, Fairhurst-Hunter Z, Koido M, Kanai M, Okada Y, Kamatani Y, Bennett D, Du H, Chen Y, Yang L, Avery D, Guo Y, Yu M, Yu C, Schmidt Valle D, Lv J, Chen J, Peto R, Collins R, Li L, Chen Z, Millwood IY, and Walters RG
Subjects: Adult, Aged, Female, Humans, Male, Middle Aged, China epidemiology, Genetic Predisposition to Disease, Genome-Wide Association Study, Hypertension genetics, Hypertension epidemiology, Mendelian Randomization Analysis, Polymorphism, Single Nucleotide, Risk Factors, Blood Pressure genetics, Cardiovascular Diseases genetics, Cardiovascular Diseases epidemiology, East Asian People genetics
Abstract: Elevated blood pressure (BP) is major risk factor for cardiovascular diseases (CVD). Genome-wide association studies (GWAS) conducted predominantly in populations of European ancestry have identified >2,000 BP-associated loci, but other ancestries have been less well-studied. We conducted GWAS of systolic, diastolic, pulse, and mean arterial BP in 100,453 Chinese adults. We identified 128 non-overlapping loci associated with one or more BP traits, including 74 newly-reported associations. Despite strong genetic correlations between populations, we identified appreciably higher heritability and larger variant effect sizes in Chinese compared with European or Japanese ancestry populations. Using instruments derived from these GWAS, multivariable Mendelian randomisation demonstrated that BP traits contribute differently to the causal associations of BP with CVD. In particular, only pulse pressure was independently causally associated with carotid plaque. These findings reinforce the need for studies in diverse populations to understand the genetic determinants of BP traits and their roles in disease risk., (© 2024. The Author(s).)
Published: 2024
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27. Proteogenomics in cerebrospinal fluid and plasma reveals new biological fingerprint of cerebral small vessel disease.

Author: Debette S, Caro I, Western D, Namba S, Sun N, Kawaguchi S, He Y, Fujita M, Roshchupkin G, D'Aoust T, Duperron MG, Sargurupremraj M, Tsuchida A, Koido M, Ahmadi M, Yang C, Timsina J, Ibanez L, Matsuda K, Suzuki Y, Oda Y, Kanai A, Jandaghi P, Munter HM, Auld D, Astafeva I, Puerta R, Rotter J, Psaty B, Bis J, Longstreth W, Couffinhal T, Garcia-Gonzalez P, Pytel V, Marquié M, Cano A, Boada M, Joliot M, Lathrop M, Le Grand Q, Launer L, Wardlaw J, Heiman M, Ruiz A, Matthews P, Seshadri S, Fornage M, Adams H, Mishra A, Trégouët DA, Okada Y, Kellis M, De Jager P, Tzourio C, Kamatani Y, Matsuda F, and Cruchaga C
Abstract: Cerebral small vessel disease (cSVD) is a leading cause of stroke and dementia with no specific mechanism-based treatment. We used Mendelian randomization to combine a unique cerebrospinal fluid (CSF) and plasma pQTL resource with the latest European-ancestry GWAS of MRI-markers of cSVD (white matter hyperintensities, perivascular spaces). We describe a new biological fingerprint of 49 protein-cSVD associations, predominantly in the CSF. We implemented a multipronged follow-up, across fluids, platforms, and ancestries (Europeans and East-Asian), including testing associations of direct plasma protein measurements with MRI-cSVD. We highlight 16 proteins robustly associated in both CSF and plasma, with 24/4 proteins identified in CSF/plasma only. cSVD-proteins were enriched in extracellular matrix and immune response pathways, and in genes enriched in microglia and specific microglial states (integration with single-nucleus RNA sequencing). Immune-related proteins were associated with MRI-cSVD already at age twenty. Half of cSVD-proteins were associated with stroke, dementia, or both, and seven cSVD-proteins are targets for known drugs (used for other indications in directions compatible with beneficial therapeutic effects. This first cSVD proteogenomic signature opens new avenues for biomarker and therapeutic developments., Competing Interests: Competing interests C.C. has received research support from GSK and EISAI and is a member of the advisory board of Circular Genomics and owns stocks in this company. CC is part of the scientific advisory board for ADmit. B.P. serves on the Steering Committee of the Yale Open Data Project funded by Johnson & Johnson. P.M.M. has received an honourarium as Chair of the UKRI Medical Research Council Neuroscience and Mental Health Board until March 2024. He acknowledges consultancy fees from, Biogen, Sudo. Nimbus and GSK. He has received speakers’ honoraria from Sanofi and Redburn, and has received research or educational funds from Biogen, Merck, Bristol Meyers Squibb and Nimbus. J.W declares no commercial COI; various academic research grants and is CI for LACunar Intervention Trials. The authors declared no potential conflicts of interest with respect to research, authorship, and/or publication of this article. The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
Published: 2024
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28. Understanding the genetic complexity of puberty timing across the allele frequency spectrum.

Author: Kentistou KA, Kaisinger LR, Stankovic S, Vaudel M, Mendes de Oliveira E, Messina A, Walters RG, Liu X, Busch AS, Helgason H, Thompson DJ, Santoni F, Petricek KM, Zouaghi Y, Huang-Doran I, Gudbjartsson DF, Bratland E, Lin K, Gardner EJ, Zhao Y, Jia RY, Terao C, Riggan MJ, Bolla MK, Yazdanpanah M, Yazdanpanah N, Bradfield JP, Broer L, Campbell A, Chasman DI, Cousminer DL, Franceschini N, Franke LH, Girotto G, He C, Järvelin MR, Joshi PK, Kamatani Y, Karlsson R, Luan J, Lunetta KL, Mägi R, Mangino M, Medland SE, Meisinger C, Noordam R, Nutile T, Concas MP, Polašek O, Porcu E, Ring SM, Sala C, Smith AV, Tanaka T, van der Most PJ, Vitart V, Wang CA, Willemsen G, Zygmunt M, Ahearn TU, Andrulis IL, Anton-Culver H, Antoniou AC, Auer PL, Barnes CLK, Beckmann MW, Berrington de Gonzalez A, Bogdanova NV, Bojesen SE, Brenner H, Buring JE, Canzian F, Chang-Claude J, Couch FJ, Cox A, Crisponi L, Czene K, Daly MB, Demerath EW, Dennis J, Devilee P, De Vivo I, Dörk T, Dunning AM, Dwek M, Eriksson JG, Fasching PA, Fernandez-Rhodes L, Ferreli L, Fletcher O, Gago-Dominguez M, García-Closas M, García-Sáenz JA, González-Neira A, Grallert H, Guénel P, Haiman CA, Hall P, Hamann U, Hakonarson H, Hart RJ, Hickey M, Hooning MJ, Hoppe R, Hopper JL, Hottenga JJ, Hu FB, Huebner H, Hunter DJ, Jernström H, John EM, Karasik D, Khusnutdinova EK, Kristensen VN, Lacey JV, Lambrechts D, Launer LJ, Lind PA, Lindblom A, Magnusson PKE, Mannermaa A, McCarthy MI, Meitinger T, Menni C, Michailidou K, Millwood IY, Milne RL, Montgomery GW, Nevanlinna H, Nolte IM, Nyholt DR, Obi N, O'Brien KM, Offit K, Oldehinkel AJ, Ostrowski SR, Palotie A, Pedersen OB, Peters A, Pianigiani G, Plaseska-Karanfilska D, Pouta A, Pozarickij A, Radice P, Rennert G, Rosendaal FR, Ruggiero D, Saloustros E, Sandler DP, Schipf S, Schmidt CO, Schmidt MK, Small K, Spedicati B, Stampfer M, Stone J, Tamimi RM, Teras LR, Tikkanen E, Turman C, Vachon CM, Wang Q, Winqvist R, Wolk A, Zemel BS, Zheng W, van Dijk KW, Alizadeh BZ, Bandinelli S, Boerwinkle E, Boomsma DI, Ciullo M, Chenevix-Trench G, Cucca F, Esko T, Gieger C, Grant SFA, Gudnason V, Hayward C, Kolčić I, Kraft P, Lawlor DA, Martin NG, Nøhr EA, Pedersen NL, Pennell CE, Ridker PM, Robino A, Snieder H, Sovio U, Spector TD, Stöckl D, Sudlow C, Timpson NJ, Toniolo D, Uitterlinden A, Ulivi S, Völzke H, Wareham NJ, Widen E, Wilson JF, Pharoah PDP, Li L, Easton DF, Njølstad PR, Sulem P, Murabito JM, Murray A, Manousaki D, Juul A, Erikstrup C, Stefansson K, Horikoshi M, Chen Z, Farooqi IS, Pitteloud N, Johansson S, Day FR, Perry JRB, and Ong KK
Subjects: Humans, Female, Animals, Multifactorial Inheritance genetics, Mice, Genome-Wide Association Study, Adolescent, Puberty, Precocious genetics, Polymorphism, Single Nucleotide, Receptors, G-Protein-Coupled genetics, Puberty, Delayed genetics, Child, Menarche genetics, Puberty genetics, Gene Frequency
Abstract: Pubertal timing varies considerably and is associated with later health outcomes. We performed multi-ancestry genetic analyses on ~800,000 women, identifying 1,080 signals for age at menarche. Collectively, these explained 11% of trait variance in an independent sample. Women at the top and bottom 1% of polygenic risk exhibited ~11 and ~14-fold higher risks of delayed and precocious puberty, respectively. We identified several genes harboring rare loss-of-function variants in ~200,000 women, including variants in ZNF483, which abolished the impact of polygenic risk. Variant-to-gene mapping approaches and mouse gonadotropin-releasing hormone neuron RNA sequencing implicated 665 genes, including an uncharacterized G-protein-coupled receptor, GPR83, which amplified the signaling of MC3R, a key nutritional sensor. Shared signals with menopause timing at genes involved in DNA damage response suggest that the ovarian reserve might signal centrally to trigger puberty. We also highlight body size-dependent and independent mechanisms that potentially link reproductive timing to later life disease., (© 2024. The Author(s).)
Published: 2024
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29. Genome-Wide Association Study with Three Control Cohorts of Japanese Patients with Esotropia and Exotropia of Comitant Strabismus and Idiopathic Superior Oblique Muscle Palsy.

Author: Matsuo T, Hamasaki I, Kamatani Y, Kawaguchi T, Yamaguchi I, Matsuda F, Saito A, Nakazono K, and Kamitsuji S
Subjects: Humans, Case-Control Studies, Cohort Studies, East Asian People genetics, Genetic Predisposition to Disease, Genotype, Japan, Esotropia genetics, Exotropia genetics, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Abstract: Esotropia and exotropia in the entity of comitant strabismus are multifactorial diseases with both genetic and environmental backgrounds. Idiopathic superior oblique muscle palsy, as the predominant entity of non-comitant (paralytic) strabismus, also has a genetic background, as evidenced by varying degrees of muscle hypoplasia. A genome-wide association study (GWAS) was conducted of 711 Japanese patients with esotropia (n= 253), exotropia (n = 356), and idiopathic superior oblique muscle palsy (n = 102). The genotypes of single nucleotide polymorphisms (SNPs) were determined by Infinium Asian Screening Array. Three control cohorts from the Japanese population were used: two cohorts from BioBank Japan (BBJ) and the Nagahama Cohort. BBJ (180K) was genotyped by a different array, Illumina Infinium OmniExpressExome or HumanOmniExpress, while BBJ (ASA) and the Nagahama Cohort were genotyped by the same Asian array. After quality control of SNPs and individuals, common SNPs between the case cohort and the control cohort were chosen in the condition of genotyping by different arrays, while all SNPs genotyped by the same array were used for SNP imputation. The SNPs imputed with R-square values ≥ 0.3 were used to compare the case cohort of each entity or the combined entity with the control cohort. In comparison with BBJ (180K), the esotropia group and the exotropia group showed CDCA7 and HLA-F , respectively, as candidate genes at a significant level of p < 5 × 10 -8 , while the idiopathic superior oblique muscle palsy group showed DAB1 as a candidate gene which is involved in neuronal migration. DAB1 was also detected as a candidate in comparison with BBJ (ASA) and the Nagahama Cohort at a weak level of significance of p < 1 × 10 -6 . In comparison with BBJ (180K), RARB (retinoic acid receptor-β) was detected as a candidate at a significant level of p < 5 × 10 -8 in the combined group of esotropia, exotropia, and idiopathic superior oblique muscle palsy. In conclusion, a series of GWASs with three different control cohorts would be an effective method with which to search for candidate genes for multifactorial diseases such as strabismus.
Published: 2024
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30. Protocol for genome-wide association study of human blood metabolites.

Author: Iwasaki T, Kamatani Y, Sonomura K, Kawaguchi S, and Matsuda F
Subjects: Humans, Metabolomics methods, Polymorphism, Single Nucleotide genetics, Genome-Wide Association Study methods, Quantitative Trait Loci genetics, Metabolome genetics
Abstract: Genetic variations influence the levels of blood metabolites. We present analytical pipelines for assessing genetic influences on human blood metabolites. We describe steps for the normalization of metabolome data, genome-wide association studies, and the identification of metabolite quantitative trait loci (mQTLs). We then detail procedures for functional enrichment analysis of mQTLs. This protocol could be applicable to other quantitative traits, such as clinical measurements or proteome data. For complete details on the use and execution of this protocol, please refer to Iwasaki et al. 1 ., Competing Interests: Declaration of interests K.S. is an employee of Shimadzu Corporation (Kyoto, Japan). S.K. and F.M. are board members of GenoConcierge Kyoto Inc. (Kyoto, Japan)., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2024
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31. Recurrent stroke prediction by applying a stroke polygenic risk score in the Japanese population.

Author: Kojima N, Koido M, He Y, Shimmori Y, Hachiya T, Japan B, Debette S, and Kamatani Y
Abstract: Background: Recently, various polygenic risk score (PRS)-based methods were developed to improve stroke prediction. However, current PRSs (including cross-ancestry PRS) poorly predict recurrent stroke. Here, we aimed to determine whether the best PRS for Japanese individuals can also predict stroke recurrence in this population by extensively comparing the methods and maximizing the predictive performance for stroke onset., Methods: We used data from the BioBank Japan (BBJ) 1 st cohort (n=179,938) to derive and optimize the PRSs using a 10-fold cross-validation. We integrated the optimized PRSs for multiple traits, such as vascular risk factors and stroke subtypes to generate a single PRS using the meta-scoring approach (metaGRS). We used an independent BBJ 2 nd cohort (n=41,929) as a test sample to evaluate the association of the metaGRS with stroke and recurrent stroke., Results: We analyzed recurrent stroke cases (n=174) and non-recurrent stroke controls (n=1,153) among subjects within the BBJ 2 nd cohort. After adjusting for known risk factors, metaGRS was associated with stroke recurrence (adjusted OR per SD 1.18 [95% CI: 1.00-1.39, p=0.044]), although no significant correlation was observed with the published PRSs. We administered three distinct tests to consider the potential index event bias; however, the outcomes derived from these examinations did not provide any significant indication of the influence of index event bias. The high metaGRS group without a history of hypertension had a higher risk of stroke recurrence than that of the low metaGRS group (adjusted OR 2.24 [95% CI: 1.07-4.66, p=0.032]). However, this association was weak in the hypertension group (adjusted OR 1.21 [95% CI: 0.69-2.13, p=0.50])., Conclusions: The metaGRS developed in a Japanese cohort predicted stroke recurrence in an independent cohort of patients. In particular, it predicted an increased risk of recurrence among stroke patients without hypertension. These findings provide clues for additional genetic risk stratification and help in developing personalized strategies for stroke recurrence prevention.
Published: 2024
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32. Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease.

Author: Malik R, Beaufort N, Li J, Tanaka K, Georgakis MK, He Y, Koido M, Terao C, Japan B, Anderson CD, Kamatani Y, Zand R, and Dichgans M
Subjects: Humans, Female, Male, Middle Aged, Japan epidemiology, Risk Assessment, Aged, Risk Factors, Polymorphism, Single Nucleotide, Phenotype, United Kingdom epidemiology, Loss of Function Mutation, High-Temperature Requirement A Serine Peptidase 1 genetics, Ischemic Stroke genetics, Ischemic Stroke blood, Ischemic Stroke epidemiology, Coronary Artery Disease genetics, Coronary Artery Disease blood, Coronary Artery Disease epidemiology, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract: Genetic variants in HTRA1 are associated with stroke risk. However, the mechanisms mediating this remain largely unknown, as does the full spectrum of phenotypes associated with genetic variation in HTRA1. Here we show that rare HTRA1 variants are linked to ischemic stroke in the UK Biobank and BioBank Japan. Integrating data from biochemical experiments, we next show that variants causing loss of protease function associated with ischemic stroke, coronary artery disease and skeletal traits in the UK Biobank and MyCode cohorts. Moreover, a common variant modulating circulating HTRA1 mRNA and protein levels enhances the risk of ischemic stroke and coronary artery disease while lowering the risk of migraine and macular dystrophy in genome-wide association study, UK Biobank, MyCode and BioBank Japan data. We found no interaction between proxied HTRA1 activity and levels. Our findings demonstrate the role of HTRA1 for cardiovascular diseases and identify two mechanisms as potential targets for therapeutic interventions., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)
Published: 2024
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33. Poor accuracy and sustainability of the first-step FIB4 EASL pathway for stratifying steatotic liver disease risk in the general population.

Author: De Vincentis A, Tavaglione F, Namba S, Kanai M, Okada Y, Kamatani Y, Maurotti S, Pedone C, Antonelli Incalzi R, Valenti L, Romeo S, and Vespasiani-Gentilucci U
Subjects: Adult, Aged, Female, Humans, Male, Middle Aged, Elasticity Imaging Techniques, Japan, Liver Cirrhosis, Non-alcoholic Fatty Liver Disease, Nutrition Surveys, Risk Assessment methods, Risk Factors, Sensitivity and Specificity, United States, Fatty Liver diagnostic imaging, Mass Screening methods
Abstract: Background and Aims: The European Association for the Study of the Liver introduced a clinical pathway (EASL CP) for screening significant/advanced fibrosis in people at risk of steatotic liver disease (SLD). We assessed the performance of the first-step FIB4 EASL CP in the general population across different SLD risk groups (MASLD, Met-ALD and ALD) and various age classes., Methods: We analysed a total of 3372 individuals at risk of SLD from the 2017-2018 National Health and Nutrition Examination Survey (NHANES17-18), projected to 152.3 million U.S. adults, 300,329 from the UK Biobank (UKBB) and 57,644 from the Biobank Japan (BBJ). We assessed liver stiffness measurement (LSM) ≥8 kPa and liver-related events occurring within 3 and 10 years (3/10 year-LREs) as outcomes. We defined MASLD, MetALD, and ALD according to recent international recommendations., Results: FIB4 sensitivity for LSM ≥ 8 kPa was low (27.7%), but it ranged approximately 80%-90% for 3-year LREs. Using FIB4, 22%-57% of subjects across the three cohorts were identified as candidates for vibration-controlled transient elastography (VCTE), which was mostly avoidable (positive predictive value of FIB4 ≥ 1.3 for LSM ≥ 8 kPa ranging 9.5%-13% across different SLD categories). Sensitivity for LSM ≥ 8 kPa and LREs increased with increasing alcohol intake (ALD>MetALD>MASLD) and age classes. For individuals aged ≥65 years, using the recommended age-adjusted FIB4 cut-off (≥2) substantially reduced sensitivity for LSM ≥ 8 kPa and LREs., Conclusions: The first-step FIB4 EASL CP is poorly accurate and feasible for individuals at risk of SLD in the general population. It is crucial to enhance the screening strategy with a first-step approach able to reduce unnecessary VCTEs and optimise their yield., (© 2024 John Wiley & Sons Ltd.)
Published: 2024
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34. Body mass index stratification optimizes polygenic prediction of type 2 diabetes in cross-biobank analyses.

Author: Ojima T, Namba S, Suzuki K, Yamamoto K, Sonehara K, Narita A, Kamatani Y, Tamiya G, Yamamoto M, Yamauchi T, Kadowaki T, and Okada Y
Subjects: Humans, Female, Male, Biological Specimen Banks, Middle Aged, Japan, Risk Factors, Aged, Polymorphism, Single Nucleotide, United Kingdom, Diabetes Mellitus, Type 2 genetics, Multifactorial Inheritance genetics, Body Mass Index, Genetic Predisposition to Disease, Genome-Wide Association Study
Abstract: Type 2 diabetes (T2D) shows heterogeneous body mass index (BMI) sensitivity. Here, we performed stratification based on BMI to optimize predictions for BMI-related diseases. We obtained BMI-stratified datasets using data from more than 195,000 individuals (n T2D = 55,284) from BioBank Japan (BBJ) and UK Biobank. T2D heritability in the low-BMI group was greater than that in the high-BMI group. Polygenic predictions of T2D toward low-BMI targets had pseudo-R 2 values that were more than 22% higher than BMI-unstratified targets. Polygenic risk scores (PRSs) from low-BMI discovery outperformed PRSs from high BMI, while PRSs from BMI-unstratified discovery performed best. Pathway-specific PRSs demonstrated the biological contributions of pathogenic pathways. Low-BMI T2D cases showed higher rates of neuropathy and retinopathy. Combining BMI stratification and a method integrating cross-population effects, T2D predictions showed greater than 37% improvements over unstratified-matched-population prediction. We replicated findings in the Tohoku Medical Megabank (n = 26,000) and the second BBJ cohort (n = 33,096). Our findings suggest that target stratification based on existing traits can improve the polygenic prediction of heterogeneous diseases., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2024
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35. Genetic variants for head size share genes and pathways with cancer.

Author: Knol MJ, Poot RA, Evans TE, Satizabal CL, Mishra A, Sargurupremraj M, van der Auwera S, Duperron MG, Jian X, Hostettler IC, van Dam-Nolen DHK, Lamballais S, Pawlak MA, Lewis CE, Carrion-Castillo A, van Erp TGM, Reinbold CS, Shin J, Scholz M, Håberg AK, Kämpe A, Li GHY, Avinun R, Atkins JR, Hsu FC, Amod AR, Lam M, Tsuchida A, Teunissen MWA, Aygün N, Patel Y, Liang D, Beiser AS, Beyer F, Bis JC, Bos D, Bryan RN, Bülow R, Caspers S, Catheline G, Cecil CAM, Dalvie S, Dartigues JF, DeCarli C, Enlund-Cerullo M, Ford JM, Franke B, Freedman BI, Friedrich N, Green MJ, Haworth S, Helmer C, Hoffmann P, Homuth G, Ikram MK, Jack CR Jr, Jahanshad N, Jockwitz C, Kamatani Y, Knodt AR, Li S, Lim K, Longstreth WT, Macciardi F, Mäkitie O, Mazoyer B, Medland SE, Miyamoto S, Moebus S, Mosley TH, Muetzel R, Mühleisen TW, Nagata M, Nakahara S, Palmer ND, Pausova Z, Preda A, Quidé Y, Reay WR, Roshchupkin GV, Schmidt R, Schreiner PJ, Setoh K, Shapland CY, Sidney S, St Pourcain B, Stein JL, Tabara Y, Teumer A, Uhlmann A, van der Lugt A, Vernooij MW, Werring DJ, Windham BG, Witte AV, Wittfeld K, Yang Q, Yoshida K, Brunner HG, Le Grand Q, Sim K, Stein DJ, Bowden DW, Cairns MJ, Hariri AR, Cheung CL, Andersson S, Villringer A, Paus T, Cichon S, Calhoun VD, Crivello F, Launer LJ, White T, Koudstaal PJ, Houlden H, Fornage M, Matsuda F, Grabe HJ, Ikram MA, Debette S, Thompson PM, Seshadri S, and Adams HHH
Subjects: Humans, Female, Male, Polymorphism, Single Nucleotide genetics, Genetic Variation, Organ Size genetics, Signal Transduction genetics, Adult, Genetic Predisposition to Disease, Genome-Wide Association Study, Head anatomy & histology, Neoplasms genetics, Neoplasms pathology
Abstract: The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread effects. Gene set enrichment is observed for various cancers and the p53, Wnt, and ErbB signaling pathways. Genes harboring lead variants are enriched for macrocephaly syndrome genes (37-fold) and high-fidelity cancer genes (9-fold), which is not seen for human height variants. Head size variants are also near genes preferentially expressed in intermediate progenitor cells, neural cells linked to evolutionary brain expansion. Our results indicate that genes regulating early brain and cranial growth incline to neoplasia later in life, irrespective of height. This warrants investigation of clinical implications of the link between head size and cancer., Competing Interests: Declaration of interests H.H. and I.C.H. received funding from Alzheimer’s Research UK and the Dunhill Medical Trust Foundation. M.A.P. reported receiving grants and personal and travel fees from Roche, Novartis, Merck, and Biogen outside the submitted work. M. Scholz receives funding from Pfizer Inc. for a project not related to this research. C.D. serves as a consultant of Novartis Pharmaceuticals. B.F. has received educational speaking fees from Medice. N.J. and P.M.T. are MPIs of a research grant from Biogen Inc. for work unrelated to the contents of this manuscript. D.J.W. received funding from the Stroke Foundation/British Heart Foundation. D.J.S. has received consultancy honoraria from Discovery Vitality, Johnson & Johnson, Kanna, L’Oreal, Lundbeck, Orion, Sanofi, Servier, Takeda, and Vistagen. H.H. received funding from MRC, Wellcome Trust, and NIHR UCLH BRC. H.J.G. has received travel grants and speaker’s honoraria from Fresenius Medical Care, Neuraxpharm, and Janssen Cilag as well as research funding from Fresenius Medical Care., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)
Published: 2024
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36. Decoding triancestral origins, archaic introgression, and natural selection in the Japanese population by whole-genome sequencing.

Author: Liu X, Koyama S, Tomizuka K, Takata S, Ishikawa Y, Ito S, Kosugi S, Suzuki K, Hikino K, Koido M, Koike Y, Horikoshi M, Gakuhari T, Ikegawa S, Matsuda K, Momozawa Y, Ito K, Kamatani Y, and Terao C
Subjects: Humans, Japan, Selection, Genetic, Whole Genome Sequencing, Exome, Diabetes Mellitus, Type 2
Abstract: We generated Japanese Encyclopedia of Whole-Genome/Exome Sequencing Library (JEWEL), a high-depth whole-genome sequencing dataset comprising 3256 individuals from across Japan. Analysis of JEWEL revealed genetic characteristics of the Japanese population that were not discernible using microarray data. First, rare variant-based analysis revealed an unprecedented fine-scale genetic structure. Together with population genetics analysis, the present-day Japanese can be decomposed into three ancestral components. Second, we identified unreported loss-of-function (LoF) variants and observed that for specific genes, LoF variants appeared to be restricted to a more limited set of transcripts than would be expected by chance, with PTPRD as a notable example. Third, we identified 44 archaic segments linked to complex traits, including a Denisovan-derived segment at NKX6-1 associated with type 2 diabetes. Most of these segments are specific to East Asians. Fourth, we identified candidate genetic loci under recent natural selection. Overall, our work provided insights into genetic characteristics of the Japanese population.
Published: 2024
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37. Identification of telomere maintenance gene variations related to lung adenocarcinoma risk by genome-wide association and whole genome sequencing analyses.

Author: Shiraishi K, Takahashi A, Momozawa Y, Daigo Y, Kaneko S, Kawaguchi T, Kunitoh H, Matsumoto S, Horinouchi H, Goto A, Honda T, Shimizu K, Torasawa M, Takayanagi D, Saito M, Saito A, Ohe Y, Watanabe SI, Goto K, Tsuboi M, Tsuchihara K, Takata S, Aoi T, Takano A, Kobayashi M, Miyagi Y, Tanaka K, Suzuki H, Maeda D, Yamaura T, Matsuda M, Shimada Y, Mizuno T, Sakamoto H, Yoshida T, Goto Y, Yoshida T, Yamaji T, Sonobe M, Toyooka S, Yoneda K, Masago K, Tanaka F, Hara M, Fuse N, Nishizuka SS, Motoi N, Sawada N, Nishida Y, Kumada K, Takeuchi K, Tanno K, Yatabe Y, Sunami K, Hishida T, Miyazaki Y, Ito H, Amemiya M, Totsuka H, Nakayama H, Yokose T, Ishigaki K, Nagashima T, Ohtaki Y, Imai K, Takasawa K, Minamiya Y, Kobayashi K, Okubo K, Wakai K, Shimizu A, Yamamoto M, Iwasaki M, Matsuda K, Inazawa J, Shiraishi Y, Nishikawa H, Murakami Y, Kubo M, Matsuda F, Kamatani Y, Hamamoto R, Matsuo K, and Kohno T
Subjects: Humans, Genome-Wide Association Study, Whole Genome Sequencing, Telomere genetics, Telomere pathology, Adenocarcinoma of Lung genetics, Lung Neoplasms genetics, Lung Neoplasms pathology
Published: 2024
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38. A large-scale microRNA transcriptome-wide association study identifies two susceptibility microRNAs, miR-1307-5p and miR-192-3p, for colorectal cancer risk.

Author: Chen Z, Lin W, Cai Q, Kweon SS, Shu XO, Tanikawa C, Jia WH, Wang Y, Su X, Yuan Y, Wen W, Kim J, Shin A, Jee SH, Matsuo K, Kim DH, Wang N, Ping J, Shin MH, Ren Z, Oh JH, Oze I, Ahn YO, Jung KJ, Gao YT, Pan ZZ, Kamatani Y, Han W, Long J, Matsuda K, Zheng W, and Guo X
Subjects: Humans, Cell Proliferation, Gene Expression Regulation, Neoplastic genetics, Genome-Wide Association Study, HCT116 Cells, Transcriptome genetics, Colorectal Neoplasms genetics, Colorectal Neoplasms metabolism, MicroRNAs genetics, MicroRNAs metabolism
Abstract: Transcriptome-wide association studies (TWAS) have identified many putative susceptibility genes for colorectal cancer (CRC) risk. However, susceptibility miRNAs, critical dysregulators of gene expression, remain unexplored. We genotyped DNA samples from 313 CRC East Asian patients and performed small RNA sequencing in their normal colon tissues distant from tumors to build genetic models for predicting miRNA expression. We applied these models and data from genome-wide association studies (GWAS) including 23 942 cases and 217 267 controls of East Asian ancestry to investigate associations of predicted miRNA expression with CRC risk. Perturbation experiments separately by promoting and inhibiting miRNAs expressions and further in vitro assays in both SW480 and HCT116 cells were conducted. At a Bonferroni-corrected threshold of P < 4.5 × 10-4, we identified two putative susceptibility miRNAs, miR-1307-5p and miR-192-3p, located in regions more than 500 kb away from any GWAS-identified risk variants in CRC. We observed that a high predicted expression of miR-1307-5p was associated with increased CRC risk, while a low predicted expression of miR-192-3p was associated with increased CRC risk. Our experimental results further provide strong evidence of their susceptible roles by showing that miR-1307-5p and miR-192-3p play a regulatory role, respectively, in promoting and inhibiting CRC cell proliferation, migration, and invasion, which was consistently observed in both SW480 and HCT116 cells. Our study provides additional insights into the biological mechanisms underlying CRC development., (© The Author(s) 2023. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.)
Published: 2024
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39. X-chromosome and kidney function: evidence from a multi-trait genetic analysis of 908,697 individuals reveals sex-specific and sex-differential findings in genes regulated by androgen response elements.

Author: Scholz M, Horn K, Pott J, Wuttke M, Kühnapfel A, Nasr MK, Kirsten H, Li Y, Hoppmann A, Gorski M, Ghasemi S, Li M, Tin A, Chai JF, Cocca M, Wang J, Nutile T, Akiyama M, Åsvold BO, Bansal N, Biggs ML, Boutin T, Brenner H, Brumpton B, Burkhardt R, Cai J, Campbell A, Campbell H, Chalmers J, Chasman DI, Chee ML, Chee ML, Chen X, Cheng CY, Cifkova R, Daviglus M, Delgado G, Dittrich K, Edwards TL, Endlich K, Michael Gaziano J, Giri A, Giulianini F, Gordon SD, Gudbjartsson DF, Hallan S, Hamet P, Hartman CA, Hayward C, Heid IM, Hellwege JN, Holleczek B, Holm H, Hutri-Kähönen N, Hveem K, Isermann B, Jonas JB, Joshi PK, Kamatani Y, Kanai M, Kastarinen M, Khor CC, Kiess W, Kleber ME, Körner A, Kovacs P, Krajcoviechova A, Kramer H, Krämer BK, Kuokkanen M, Kähönen M, Lange LA, Lash JP, Lehtimäki T, Li H, Lin BM, Liu J, Loeffler M, Lyytikäinen LP, Magnusson PKE, Martin NG, Matsuda K, Milaneschi Y, Mishra PP, Mononen N, Montgomery GW, Mook-Kanamori DO, Mychaleckyj JC, März W, Nauck M, Nikus K, Nolte IM, Noordam R, Okada Y, Olafsson I, Oldehinkel AJ, Penninx BWJH, Perola M, Pirastu N, Polasek O, Porteous DJ, Poulain T, Psaty BM, Rabelink TJ, Raffield LM, Raitakari OT, Rasheed H, Reilly DF, Rice KM, Richmond A, Ridker PM, Rotter JI, Rudan I, Sabanayagam C, Salomaa V, Schneiderman N, Schöttker B, Sims M, Snieder H, Stark KJ, Stefansson K, Stocker H, Stumvoll M, Sulem P, Sveinbjornsson G, Svensson PO, Tai ES, Taylor KD, Tayo BO, Teren A, Tham YC, Thiery J, Thio CHL, Thomas LF, Tremblay J, Tönjes A, van der Most PJ, Vitart V, Völker U, Wang YX, Wang C, Wei WB, Whitfield JB, Wild SH, Wilson JF, Winkler TW, Wong TY, Woodward M, Sim X, Chu AY, Feitosa MF, Thorsteinsdottir U, Hung AM, Teumer A, Franceschini N, Parsa A, Köttgen A, Schlosser P, and Pattaro C
Subjects: Humans, Male, Female, Kidney, Chromosomes, Human, X genetics, Response Elements, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Tetraspanins genetics, Androgens genetics, Genome-Wide Association Study
Abstract: X-chromosomal genetic variants are understudied but can yield valuable insights into sexually dimorphic human traits and diseases. We performed a sex-stratified cross-ancestry X-chromosome-wide association meta-analysis of seven kidney-related traits (n = 908,697), identifying 23 loci genome-wide significantly associated with two of the traits: 7 for uric acid and 16 for estimated glomerular filtration rate (eGFR), including four novel eGFR loci containing the functionally plausible prioritized genes ACSL4, CLDN2, TSPAN6 and the female-specific DRP2. Further, we identified five novel sex-interactions, comprising male-specific effects at FAM9B and AR/EDA2R, and three sex-differential findings with larger genetic effect sizes in males at DCAF12L1 and MST4 and larger effect sizes in females at HPRT1. All prioritized genes in loci showing significant sex-interactions were located next to androgen response elements (ARE). Five ARE genes showed sex-differential expressions. This study contributes new insights into sex-dimorphisms of kidney traits along with new prioritized gene targets for further molecular research., (© 2024. The Author(s).)
Published: 2024
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40. East Asian-specific and cross-ancestry genome-wide meta-analyses provide mechanistic insights into peptic ulcer disease.

Author: He Y, Koido M, Sutoh Y, Shi M, Otsuka-Yamasaki Y, Munter HM, Morisaki T, Nagai A, Murakami Y, Tanikawa C, Hachiya T, Matsuda K, Shimizu A, and Kamatani Y
Subjects: Humans, East Asian People, Genome-Wide Association Study, Peptic Ulcer genetics, Peptic Ulcer complications, Stomach Ulcer etiology, Duodenal Ulcer genetics, Duodenal Ulcer complications, Duodenal Ulcer diagnosis
Abstract: Peptic ulcer disease (PUD) refers to acid-induced injury of the digestive tract, occurring mainly in the stomach (gastric ulcer (GU)) or duodenum (duodenal ulcer (DU)). In the present study, we conducted a large-scale, cross-ancestry meta-analysis of PUD combining genome-wide association studies with Japanese and European studies (52,032 cases and 905,344 controls), and discovered 25 new loci highly concordant across ancestries. An examination of GU and DU genetic architecture demonstrated that GUs shared the same risk loci as DUs, although with smaller genetic effect sizes and higher polygenicity than DUs, indicating higher heterogeneity of GUs. Helicobacter pylori (HP)-stratified analysis found an HP-related host genetic locus. Integrative analyses using bulk and single-cell transcriptome profiles highlighted the genetic factors of PUD being enriched in the highly expressed genes in stomach tissues, especially in somatostatin-producing D cells. Our results provide genetic evidence that gastrointestinal cell differentiations and hormone regulations are critical in PUD etiology., (© 2023. The Author(s).)
Published: 2023
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41. Genetic risk score of cerebral infarction in atrial fibrillation genome-wide association study.

Author: Ebana Y, Liu L, Ihara K, Abe K, Terao C, Kamatani Y, Sasano T, and Furukawa T
Subjects: Adult, Humans, Genome-Wide Association Study, Risk Assessment, Risk Factors, Cerebral Infarction epidemiology, Cerebral Infarction genetics, Cerebral Infarction complications, Predictive Value of Tests, Atrial Fibrillation complications, Atrial Fibrillation epidemiology, Atrial Fibrillation genetics, Stroke epidemiology, Stroke genetics, Stroke complications
Abstract: Introduction: Stroke is a leading cause of death and the primary cause of adult-acquired disability. Patients with cardiogenic embolic stroke also have higher mortality and recurrence rates than patients with other stroke subtypes. Atrial fibrillation (AF) is a major risk factor for cerebral infarction (CI). The large-scale study identified 32 loci in the MEGASTROKE study. However, few studies have attempted to identify novel stroke risk variants in patients with a history of AF. Our overall aim was to identify novel CI risk variants in AF cases and explore whether their associations with the CI risk were affected by the CHADS2 and CHA2DS2-VASc scores., Methods: We performed association study with CI using 8181 AF cases in previous genome-wide association study (GWAS) and imputation data without controls. We classified AF cases into those with or without past history of CI, and the genetic associations with the CI risk were examined., Results: GWAS identified eight associated loci. The generated genetic risk score (GRS) for the eight loci was significantly associated with CI in patients with AF (1.46 × 10 -8 ). We estimated bivariate logistic regression model which contained GRS and CHADS2 score (GRS: p-Value = 7.41 × 10 -9 , CHADS2 score: p-Value <2.0 × 10 -16 ) or CHA2DS2-VASc scores (GRS: p-Value = 2.52 × 10 -10 , CHA2DS2-VASc score: p-Value <2.0 × 10 -16 )., Conclusion: We identified eight genetic variants that were potentially associated with the risk of CI of AF cases and the significant GRS, whose associations were independent of the CHADS2 or CHA2DS2-VASc score., (© 2023 Stichting European Society for Clinical Investigation Journal Foundation. Published by John Wiley & Sons Ltd.)
Published: 2023
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42. Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants.

Author: Wang A, Shen J, Rodriguez AA, Saunders EJ, Chen F, Janivara R, Darst BF, Sheng X, Xu Y, Chou AJ, Benlloch S, Dadaev T, Brook MN, Plym A, Sahimi A, Hoffman TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Laisk T, Figuerêdo J, Muir K, Ito S, Liu X, Uchio Y, Kubo M, Kamatani Y, Lophatananon A, Wan P, Andrews C, Lori A, Choudhury PP, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokolorczyk D, Lubinski J, Rentsch CT, Cho K, Mcmahon BH, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder A, Stroomberg HV, Batra J, Chambers S, Horvath L, Clements JA, Tilly W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordstrom T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein S, Cook MB, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM Jr, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Koutros S, Beane Freeman LE, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Butler EN, Mohler JL, Taylor JA, Kogevinas M, Dierssen-Sotos T, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Pilie P, Yu Y, Bohlender RJ, Gu J, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Brenner H, Chen X, Holleczek B, Schöttker B, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas CM, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Abraham A, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen J, Petrovics G, Casey G, Wang Y, Tettey Y, Lachance J, Tang W, Biritwum RB, Adjei AA, Tay E, Truelove A, Niwa S, Yamoah K, Govindasami K, Chokkalingam AP, Keaton JM, Hellwege JN, Clark PE, Jalloh M, Gueye SM, Niang L, Ogunbiyi O, Shittu O, Amodu O, Adebiyi AO, Aisuodionoe-Shadrach OI, Ajibola HO, Jamda MA, Oluwole OP, Nwegbu M, Adusei B, Mante S, Darkwa-Abrahams A, Diop H, Gundell SM, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Kachuri L, Varma R, McKean-Cowdin R, Torres M, Preuss MH, Loos RJF, Zawistowski M, Zöllner S, Lu Z, Van Den Eeden SK, Easton DF, Ambs S, Edwards TL, Mägi R, Rebbeck TR, Fritsche L, Chanock SJ, Berndt SI, Wiklund F, Nakagawa H, Witte JS, Gaziano JM, Justice AC, Mancuso N, Terao C, Eeles RA, Kote-Jarai Z, Madduri RK, Conti DV, and Haiman CA
Subjects: Humans, Male, Black People genetics, Genome-Wide Association Study, Hispanic or Latino genetics, Polymorphism, Single Nucleotide, Risk Factors, White People genetics, Asian People genetics, Genetic Predisposition to Disease, Prostatic Neoplasms genetics
Abstract: The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2023
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43. Genotype imputation accuracy and the quality metrics of the minor ancestry in multi-ancestry reference panels.

Author: Shi M, Tanikawa C, Munter HM, Akiyama M, Koyama S, Tomizuka K, Matsuda K, Lathrop GM, Terao C, Koido M, and Kamatani Y
Subjects: Humans, Gene Frequency, Genotype, Genome-Wide Association Study, Polymorphism, Single Nucleotide
Abstract: Large-scale imputation reference panels are currently available and have contributed to efficient genome-wide association studies through genotype imputation. However, whether large-size multi-ancestry or small-size population-specific reference panels are the optimal choices for under-represented populations continues to be debated. We imputed genotypes of East Asian (180k Japanese) subjects using the Trans-Omics for Precision Medicine reference panel and found that the standard imputation quality metric (Rsq) overestimated dosage r2 (squared correlation between imputed dosage and true genotype) particularly in marginal-quality bins. Variance component analysis of Rsq revealed that the increased imputed-genotype certainty (dosages closer to 0, 1 or 2) caused upward bias, indicating some systemic bias in the imputation. Through systematic simulations using different template switching rates (θ value) in the hidden Markov model, we revealed that the lower θ value increased the imputed-genotype certainty and Rsq; however, dosage r2 was insensitive to the θ value, thereby causing a deviation. In simulated reference panels with different sizes and ancestral diversities, the θ value estimates from Minimac decreased with the size of a single ancestry and increased with the ancestral diversity. Thus, Rsq could be deviated from dosage r2 for a subpopulation in the multi-ancestry panel, and the deviation represents different imputed-dosage distributions. Finally, despite the impact of the θ value, distant ancestries in the reference panel contributed only a few additional variants passing a predefined Rsq threshold. We conclude that the θ value substantially impacts the imputed dosage and the imputation quality metric value., (© The Author(s) 2024. Published by Oxford University Press.)
Published: 2023
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44. Genetically proxied HTRA1 protease activity and circulating levels independently predict risk of ischemic stroke and coronary artery disease.

Author: Dichgans M, Malik R, Beaufort N, Tanaka K, Georgakis M, He Y, Koido M, Terao C, Anderson C, and Kamatani Y
Abstract: HTRA1 has emerged as a major risk gene for stroke and cerebral small vessel disease with both rare and common variants contributing to disease risk. However, the precise mechanisms mediating this risk remain largely unknown as does the full spectrum of phenotypes associated with genetic variation in HTRA1 in the general population. Using a family-history informed approach, we first show that rare variants in HTRA1 are linked to ischemic stroke in 425,338 European individuals from the UK Biobank with replication in 143,149 individuals from the Biobank Japan. Integrating data from biochemical experiments on 76 mutations occurring in the UK Biobank, we next show that rare variants causing loss of protease function in vitro associate with ischemic stroke, coronary artery disease, and skeletal traits. In addition, a common causal variant (rs2672592) modulating circulating HTRA1 mRNA and protein levels enhances the risk of ischemic stroke, small vessel stroke, and coronary artery disease while lowering the risk of migraine and age-related macular dystrophy in GWAS and UK Biobank data from > 2,000,000 individuals. There was no evidence of an interaction between genetically proxied HTRA1 activity and levels. Our findings demonstrate a central role of HTRA1 for human disease including stroke and coronary artery disease and identify two independent mechanisms that might qualify as targets for future therapeutic interventions., Competing Interests: COMPETING INTERESTS C.D.A. has received sponsored research support from Bayer AG, and has consulted for ApoPharma, unrelated to the content of this manuscript. All other authors declare no competing interests.
Published: 2023
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45. Boosting the power of genome-wide association studies within and across ancestries by using polygenic scores.

Author: Campos AI, Namba S, Lin SC, Nam K, Sidorenko J, Wang H, Kamatani Y, Wang LH, Lee S, Lin YF, Feng YA, Okada Y, Visscher PM, and Yengo L
Subjects: Humans, Phenotype, Polymorphism, Single Nucleotide, Genome-Wide Association Study methods, Multifactorial Inheritance, East Asian People genetics
Abstract: Genome-wide association studies (GWASs) have been mostly conducted in populations of European ancestry, which currently limits the transferability of their findings to other populations. Here, we show, through theory, simulations and applications to real data, that adjustment of GWAS analyses for polygenic scores (PGSs) increases the statistical power for discovery across all ancestries. We applied this method to analyze seven traits available in three large biobanks with participants of East Asian ancestry (n = 340,000 in total) and report 139 additional associations across traits. We also present a two-stage meta-analysis strategy whereby, in contributing cohorts, a PGS-adjusted GWAS is rerun using PGSs derived from a first round of a standard meta-analysis. On average, across traits, this approach yields a 1.26-fold increase in the number of detected associations (range 1.07- to 1.76-fold increase). Altogether, our study demonstrates the value of using PGSs to increase the power of GWASs in underrepresented populations and promotes such an analytical strategy for future GWAS meta-analyses., (© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.)
Published: 2023
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46. Androgen receptor binding sites enabling genetic prediction of mortality due to prostate cancer in cancer-free subjects.

Author: Ito S, Liu X, Ishikawa Y, Conti DD, Otomo N, Kote-Jarai Z, Suetsugu H, Eeles RA, Koike Y, Hikino K, Yoshino S, Tomizuka K, Horikoshi M, Ito K, Uchio Y, Momozawa Y, Kubo M, Kamatani Y, Matsuda K, Haiman CA, Ikegawa S, Nakagawa H, and Terao C
Subjects: Humans, Male, Androgens, Binding Sites genetics, Multifactorial Inheritance, Receptors, Androgen genetics, Neoplasms, Second Primary, Prostatic Neoplasms genetics
Abstract: Prostate cancer (PrCa) is the second most common cancer worldwide in males. While strongly warranted, the prediction of mortality risk due to PrCa, especially before its development, is challenging. Here, we address this issue by maximizing the statistical power of genetic data with multi-ancestry meta-analysis and focusing on binding sites of the androgen receptor (AR), which has a critical role in PrCa. Taking advantage of large Japanese samples ever, a multi-ancestry meta-analysis comprising more than 300,000 subjects in total identifies 9 unreported loci including ZFHX3, a tumor suppressor gene, and successfully narrows down the statistically finemapped variants compared to European-only studies, and these variants strongly enrich in AR binding sites. A polygenic risk scores (PRS) analysis restricting to statistically finemapped variants in AR binding sites shows among cancer-free subjects, individuals with a PRS in the top 10% have a strongly higher risk of the future death of PrCa (HR: 5.57, P = 4.2 × 10 -10 ). Our findings demonstrate the potential utility of leveraging large-scale genetic data and advanced analytical methods in predicting the mortality of PrCa., (© 2023. Springer Nature Limited.)
Published: 2023
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47. Hyperfructosemia in sleep disordered breathing: metabolome analysis of Nagahama study.

Author: Nakatsuka Y, Murase K, Sonomura K, Tabara Y, Nagasaki T, Hamada S, Matsumoto T, Minami T, Kanai O, Takeyama H, Sunadome H, Takahashi N, Nakamoto I, Tanizawa K, Handa T, Sato TA, Komenami N, Wakamura T, Morita S, Takeuchi O, Nakayama T, Hirai T, Kamatani Y, Matsuda F, and Chin K
Subjects: Humans, Continuous Positive Airway Pressure, Multivariate Analysis, Metabolome, Sleep Apnea Syndromes therapy, Sleep Apnea, Obstructive complications
Abstract: Sleep disordered breathing (SDB), mainly obstructive sleep apnea (OSA), constitutes a major health problem due to the large number of patients. Intermittent hypoxia caused by SDB induces alterations in metabolic function. Nevertheless, metabolites characteristic for SDB are largely unknown. In this study, we performed gas chromatography-mass spectrometry-based targeted metabolome analysis using data from The Nagahama Study (n = 6373). SDB-related metabolites were defined based on their variable importance score in orthogonal partial least squares discriminant analysis and fold changes in normalized peak-intensity levels between moderate-severe SDB patients and participants without SDB. We identified 20 metabolites as SDB-related, and interestingly, these metabolites were frequently included in pathways related to fructose. Multivariate analysis revealed that moderate-severe SDB was a significant factor for increased plasma fructose levels (β = 0.210, P = 0.006, generalized linear model) even after the adjustment of confounding factors. We further investigated changes in plasma fructose levels after continuous positive airway pressure (CPAP) treatment using samples from patients with OSA (n = 60) diagnosed by polysomnography at Kyoto University Hospital, and found that patients with marked hypoxemia exhibited prominent hyperfructosemia and their plasma fructose levels lowered after CPAP treatment. These data suggest that hyperfructosemia is the abnormality characteristic to SDB, which can be reduced by CPAP treatment., (© 2023. Springer Nature Limited.)
Published: 2023
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48. Genome-wide Association Studies Categorized by Class of Antihypertensive Drugs Reveal Complex Pathogenesis of Hypertension with Drug Resistance.

Author: Yamazaki K, Terao C, Takahashi A, Kamatani Y, Matsuda K, Asai S, and Takahashi Y
Subjects: Humans, Genome-Wide Association Study, Calcium Channel Blockers therapeutic use, Blood Pressure, Drug Resistance, Antihypertensive Agents therapeutic use, Antihypertensive Agents pharmacology, Hypertension drug therapy, Hypertension genetics
Abstract: Resistant hypertension is defined as uncontrolled blood pressure (BP) despite the use of three or more antihypertensive drugs of different classes. Although genetic factors may greatly contribute to hypertension with resistance to multiple drug classes, more than for general hypertension, its pathogenesis remains unknown. To reveal the genetic background of resistant hypertension, we categorized 32,239 patients whose data were obtained from the BioBank Japan Project, by prescription of 7 classes of antihypertensive drugs and performed genome-wide association studies (GWAS). Our GWAS identified four loci with significant association (P < 5 × 10 -8 ): rs6445583 in CACNA1D and rs12308051 in the intergenic region on chromosome 12 for angiotensin II receptor blockers, rs35497065 in FOXA3 for calcium channel blockers, and rs11066280 in HECTD4 for αβ-blockers. Because these loci are known to be susceptibility loci for hypertension and/or BP, our results indicate that resistant hypertension is caused by a combination of excessive BP and drug resistance to each antihypertensive pharmacological class. Furthermore, to investigate the genetic difference between BP traits and the treatment effectiveness of antihypertensive drugs, we performed gene-set analysis and calculated the genetic correlation continuously. Most of the genetic factors were in common between BP traits and antihypertensive effectiveness, but it seems that the genetic architecture of the drug response to antihypertensive treatment is more complicated than BP traits. This corresponds to the well-known mosaic theory of hypertension. Our findings reveal the complex pathogenesis of hypertension with resistance to multiple classes of antihypertensive drugs., (© 2023 The Authors. Clinical Pharmacology & Therapeutics © 2023 American Society for Clinical Pharmacology and Therapeutics.)
Published: 2023
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49. Genetic insights into ossification of the posterior longitudinal ligament of the spine.

Author: Koike Y, Takahata M, Nakajima M, Otomo N, Suetsugu H, Liu X, Endo T, Imagama S, Kobayashi K, Kaito T, Kato S, Kawaguchi Y, Kanayama M, Sakai H, Tsuji T, Miyamoto T, Inose H, Yoshii T, Kashii M, Nakashima H, Ando K, Taniguchi Y, Takeuchi K, Ito S, Tomizuka K, Hikino K, Iwasaki Y, Kamatani Y, Maeda S, Nakajima H, Mori K, Seichi A, Fujibayashi S, Kanchiku T, Watanabe K, Tanaka T, Kida K, Kobayashi S, Takahashi M, Yamada K, Takuwa H, Lu HF, Niida S, Ozaki K, Momozawa Y, Yamazaki M, Okawa A, Matsumoto M, Iwasaki N, Terao C, and Ikegawa S
Subjects: Animals, Mice, Osteogenesis, Genome-Wide Association Study, Spine pathology, Diabetes Mellitus, Type 2 pathology, Ossification of Posterior Longitudinal Ligament genetics, Ossification of Posterior Longitudinal Ligament pathology
Abstract: Ossification of the posterior longitudinal ligament of the spine (OPLL) is an intractable disease leading to severe neurological deficits. Its etiology and pathogenesis are primarily unknown. The relationship between OPLL and comorbidities, especially type 2 diabetes (T2D) and high body mass index (BMI), has been the focus of attention; however, no trait has been proven to have a causal relationship. We conducted a meta-analysis of genome-wide association studies (GWASs) using 22,016 Japanese individuals and identified 14 significant loci, 8 of which were previously unreported. We then conducted a gene-based association analysis and a transcriptome-wide Mendelian randomization approach and identified three candidate genes for each. Partitioning heritability enrichment analyses observed significant enrichment of the polygenic signals in the active enhancers of the connective/bone cell group, especially H3K27ac in chondrogenic differentiation cells, as well as the immune/hematopoietic cell group. Single-cell RNA sequencing of Achilles tendon cells from a mouse Achilles tendon ossification model confirmed the expression of genes in GWAS and post-GWAS analyses in mesenchymal and immune cells. Genetic correlations with 96 complex traits showed positive correlations with T2D and BMI and a negative correlation with cerebral aneurysm. Mendelian randomization analysis demonstrated a significant causal effect of increased BMI and high bone mineral density on OPLL. We evaluated the clinical images in detail and classified OPLL into cervical, thoracic, and the other types. GWAS subanalyses identified subtype-specific signals. A polygenic risk score for BMI demonstrated that the effect of BMI was particularly strong in thoracic OPLL. Our study provides genetic insight into the etiology and pathogenesis of OPLL and is expected to serve as a basis for future treatment development., Competing Interests: YK, MT, MN, NO, HS, XL, TE, SI, KK, TK, SK, MK, HS, TT, TM, HI, TY, MK, HN, KA, YT, KT, SI, KT, KH, YI, YK, SM, HN, KM, AS, SF, TK, KW, TT, KK, SK, MT, KY, HT, HL, SN, KO, YM, AO, MM, NI, CT, SI No competing interests declared, YK Consulting fees from Medacta International, MY representatives of Japanese Organization of the Study for Ossification of Spinal Ligament, (© 2023, Koike, Takahata, Nakajima et al.)
Published: 2023
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50. Author Correction: The high-dimensional space of human diseases built from diagnosis records and mapped to genetic loci.

Author: Jia G, Li Y, Zhong X, Wang K, Pividori M, Alomairy R, Esposito A, Ltaief H, Terao C, Akiyama M, Matsuda K, Keyes DE, Im HK, Gojobori T, Kamatani Y, Kubo M, Cox NJ, Evans J, Gao X, and Rzhetsky A
Published: 2023
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