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619 results on '"Akiyama, Masato"'

1. Population-specific putative causal variants shape quantitative traits

Author

Koyama, Satoshi, Liu, Xiaoxi, Koike, Yoshinao, Hikino, Keiko, Koido, Masaru, Li, Wei, Akaki, Kotaro, Tomizuka, Kohei, Ito, Shuji, Otomo, Nao, Suetsugu, Hiroyuki, Yoshino, Soichiro, Akiyama, Masato, Saito, Kohei, Ishikawa, Yuki, Benner, Christian, Natarajan, Pradeep, Ellinor, Patrick T., Mushiroda, Taisei, Horikoshi, Momoko, Ikeda, Masashi, Iwata, Nakao, Matsuda, Koichi, Niida, Shumpei, Ozaki, Kouichi, Momozawa, Yukihide, Ikegawa, Shiro, Takeuchi, Osamu, Ito, Kaoru, and Terao, Chikashi

Published
2024
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5. 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, Markus, Horn, Katrin, Pott, Janne, Wuttke, Matthias, Kühnapfel, Andreas, Nasr, M, Kirsten, Holger, Li, Yong, Hoppmann, Anselm, Gorski, Mathias, Ghasemi, Sahar, Li, Man, Tin, Adrienne, Chai, Jin-Fang, Cocca, Massimiliano, Wang, Judy, Nutile, Teresa, Akiyama, Masato, Åsvold, Bjørn, Bansal, Nisha, Biggs, Mary, Boutin, Thibaud, Brenner, Hermann, Brumpton, Ben, Burkhardt, Ralph, Cai, Jianwen, Campbell, Archie, Campbell, Harry, Chalmers, John, Chasman, Daniel, Chee, Miao, Chen, Xu, Cheng, Ching-Yu, Cifkova, Renata, Daviglus, Martha, Delgado, Graciela, Dittrich, Katalin, Edwards, Todd, Endlich, Karlhans, Michael Gaziano, J, Giri, Ayush, Giulianini, Franco, Gordon, Scott, Gudbjartsson, Daniel, Hallan, Stein, Hamet, Pavel, Hartman, Catharina, Hayward, Caroline, Heid, Iris, Hellwege, Jacklyn, Holleczek, Bernd, Holm, Hilma, Hutri-Kähönen, Nina, Hveem, Kristian, Isermann, Berend, Jonas, Jost, Joshi, Peter, Kamatani, Yoichiro, Kanai, Masahiro, Kastarinen, Mika, Khor, Chiea, Kiess, Wieland, Kleber, Marcus, Körner, Antje, Kovacs, Peter, Krajcoviechova, Alena, Kramer, Holly, Krämer, Bernhard, Kuokkanen, Mikko, Kähönen, Mika, Lange, Leslie, Lash, James, Lehtimäki, Terho, Li, Hengtong, Lin, Bridget, Liu, Jianjun, Loeffler, Markus, Lyytikäinen, Leo-Pekka, Magnusson, Patrik, Martin, Nicholas, Matsuda, Koichi, Milaneschi, Yuri, Mishra, Pashupati, Mononen, Nina, Montgomery, Grant, Mook-Kanamori, Dennis, Mychaleckyj, Josyf, März, Winfried, Nauck, Matthias, Nikus, Kjell, Nolte, Ilja, Noordam, Raymond, Okada, Yukinori, Olafsson, Isleifur, Oldehinkel, Albertine, Penninx, Brenda, Perola, Markus, Pirastu, Nicola, and Polasek, Ozren

Subjects
Humans, Male, Female, Androgens, Genome-Wide Association Study, Kidney, Chromosomes, Human, X, Response Elements, Polymorphism, Single Nucleotide, Genetic Predisposition to Disease, Tetraspanins
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.

Published
2024

6. Genome-wide meta-analysis identifies 22 loci for normal tension glaucoma with significant overlap with high tension glaucoma

Author

Diaz-Torres, Santiago, He, Weixiong, Yu, Regina, Khawaja, Anthony P., Hammond, Christopher J., Hysi, Pirro G., Pasquale, Louis R., Wu, Yeda, Kubo, Michiaki, Akiyama, Masato, Aung, Tin, Cheng, Ching-Yu, Khor, Chiea Chuen, Kraft, Peter, Kang, Jae H., Hewitt, Alex W., Mackey, David A., Craig, Jamie E., Wiggs, Janey L., Ong, Jue-Sheng, MacGregor, Stuart, and Gharahkhani, Puya

Published
2024
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9. Genetic diversity fuels gene discovery for tobacco and alcohol use

Author

Saunders, Gretchen RB, Wang, Xingyan, Chen, Fang, Jang, Seon-Kyeong, Liu, Mengzhen, Wang, Chen, Gao, Shuang, Jiang, Yu, Khunsriraksakul, Chachrit, Otto, Jacqueline M, Addison, Clifton, Akiyama, Masato, Albert, Christine M, Aliev, Fazil, Alonso, Alvaro, Arnett, Donna K, Ashley-Koch, Allison E, Ashrani, Aneel A, Barnes, Kathleen C, Barr, R Graham, Bartz, Traci M, Becker, Diane M, Bielak, Lawrence F, Benjamin, Emelia J, Bis, Joshua C, Bjornsdottir, Gyda, Blangero, John, Bleecker, Eugene R, Boardman, Jason D, Boerwinkle, Eric, Boomsma, Dorret I, Boorgula, Meher Preethi, Bowden, Donald W, Brody, Jennifer A, Cade, Brian E, Chasman, Daniel I, Chavan, Sameer, Chen, Yii-Der Ida, Chen, Zhengming, Cheng, Iona, Cho, Michael H, Choquet, Hélène, Cole, John W, Cornelis, Marilyn C, Cucca, Francesco, Curran, Joanne E, de Andrade, Mariza, Dick, Danielle M, Docherty, Anna R, Duggirala, Ravindranath, Eaton, Charles B, Ehringer, Marissa A, Esko, Tõnu, Faul, Jessica D, Fernandes Silva, Lilian, Fiorillo, Edoardo, Fornage, Myriam, Freedman, Barry I, Gabrielsen, Maiken E, Garrett, Melanie E, Gharib, Sina A, Gieger, Christian, Gillespie, Nathan, Glahn, David C, Gordon, Scott D, Gu, Charles C, Gu, Dongfeng, Gudbjartsson, Daniel F, Guo, Xiuqing, Haessler, Jeffrey, Hall, Michael E, Haller, Toomas, Harris, Kathleen Mullan, He, Jiang, Herd, Pamela, Hewitt, John K, Hickie, Ian, Hidalgo, Bertha, Hokanson, John E, Hopfer, Christian, Hottenga, JoukeJan, Hou, Lifang, Huang, Hongyan, Hung, Yi-Jen, Hunter, David J, Hveem, Kristian, Hwang, Shih-Jen, Hwu, Chii-Min, Iacono, William, Irvin, Marguerite R, Jee, Yon Ho, Johnson, Eric O, Joo, Yoonjung Y, Jorgenson, Eric, Justice, Anne E, Kamatani, Yoichiro, Kaplan, Robert C, Kaprio, Jaakko, Kardia, Sharon LR, and Keller, Matthew C

Subjects
Genetics, Alcoholism, Alcohol Use and Health, Prevention, Human Genome, Substance Misuse, Aetiology, 2.1 Biological and endogenous factors, Cancer, Good Health and Well Being, Humans, Genetic Predisposition to Disease, Genetic Variation, Genome-Wide Association Study, Multifactorial Inheritance, Risk Factors, Tobacco Use, Alcohol Drinking, Transcriptome, Sample Size, Genetic Loci, Internationality, Europe, 23andMe Research Team, Biobank Japan Project, General Science & Technology
Abstract

Tobacco and alcohol use are heritable behaviours associated with 15% and 5.3% of worldwide deaths, respectively, due largely to broad increased risk for disease and injury1-4. These substances are used across the globe, yet genome-wide association studies have focused largely on individuals of European ancestries5. Here we leveraged global genetic diversity across 3.4 million individuals from four major clines of global ancestry (approximately 21% non-European) to power the discovery and fine-mapping of genomic loci associated with tobacco and alcohol use, to inform function of these loci via ancestry-aware transcriptome-wide association studies, and to evaluate the genetic architecture and predictive power of polygenic risk within and across populations. We found that increases in sample size and genetic diversity improved locus identification and fine-mapping resolution, and that a large majority of the 3,823 associated variants (from 2,143 loci) showed consistent effect sizes across ancestry dimensions. However, polygenic risk scores developed in one ancestry performed poorly in others, highlighting the continued need to increase sample sizes of diverse ancestries to realize any potential benefit of polygenic prediction.

Published
2022

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

Author

Yengo, Loïc, Vedantam, Sailaja, Marouli, Eirini, Sidorenko, Julia, Bartell, Eric, Sakaue, Saori, Graff, Marielisa, Eliasen, Anders U, Jiang, Yunxuan, Raghavan, Sridharan, Miao, Jenkai, Arias, Joshua D, Graham, Sarah E, Mukamel, Ronen E, Spracklen, Cassandra N, Yin, Xianyong, Chen, Shyh-Huei, Ferreira, Teresa, Highland, Heather H, Ji, Yingjie, Karaderi, Tugce, Lin, Kuang, Lüll, Kreete, Malden, Deborah E, Medina-Gomez, Carolina, Machado, Moara, Moore, Amy, Rüeger, Sina, Sim, Xueling, Vrieze, Scott, Ahluwalia, Tarunveer S, Akiyama, Masato, Allison, Matthew A, Alvarez, Marcus, Andersen, Mette K, Ani, Alireza, Appadurai, Vivek, Arbeeva, Liubov, Bhaskar, Seema, Bielak, Lawrence F, Bollepalli, Sailalitha, Bonnycastle, Lori L, Bork-Jensen, Jette, Bradfield, Jonathan P, Bradford, Yuki, Braund, Peter S, Brody, Jennifer A, Burgdorf, Kristoffer S, Cade, Brian E, Cai, Hui, Cai, Qiuyin, Campbell, Archie, Cañadas-Garre, Marisa, Catamo, Eulalia, Chai, Jin-Fang, Chai, Xiaoran, Chang, Li-Ching, Chang, Yi-Cheng, Chen, Chien-Hsiun, Chesi, Alessandra, Choi, Seung Hoan, Chung, Ren-Hua, Cocca, Massimiliano, Concas, Maria Pina, Couture, Christian, Cuellar-Partida, Gabriel, Danning, Rebecca, Daw, E Warwick, Degenhard, Frauke, Delgado, Graciela E, Delitala, Alessandro, Demirkan, Ayse, Deng, Xuan, Devineni, Poornima, Dietl, Alexander, Dimitriou, Maria, Dimitrov, Latchezar, Dorajoo, Rajkumar, Ekici, Arif B, Engmann, Jorgen E, Fairhurst-Hunter, Zammy, Farmaki, Aliki-Eleni, Faul, Jessica D, Fernandez-Lopez, Juan-Carlos, Forer, Lukas, Francescatto, Margherita, Freitag-Wolf, Sandra, Fuchsberger, Christian, Galesloot, Tessel E, Gao, Yan, Gao, Zishan, Geller, Frank, Giannakopoulou, Olga, Giulianini, Franco, Gjesing, Anette P, Goel, Anuj, Gordon, Scott D, Gorski, Mathias, Grove, Jakob, and Guo, Xiuqing

Subjects
Epidemiology, Biological Sciences, Health Sciences, Genetics, Human Genome, Humans, Body Height, Gene Frequency, Genome, Human, Genome-Wide Association Study, Haplotypes, Linkage Disequilibrium, Polymorphism, Single Nucleotide, Europe, Sample Size, Phenotype, Chromosome Mapping, 23andMe Research Team, VA Million Veteran Program, DiscovEHR, eMERGE, Lifelines Cohort Study, PRACTICAL Consortium, Understanding Society Scientific Group, General Science & Technology
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. Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals

Author

Matsuda, Koichi, Yamanashi, Yuji, Furukawa, Yoichi, Morisaki, Takayuki, Okada, Yukinori, Murakami, Yoshinori, Muto, Kaori, Nagai, Akiko, Nakamura, Yusuke, Obara, Wataru, Yamaji, Ken, Takahashi, Kazuhisa, Asai, Satoshi, Takahashi, Yasuo, Higashiue, Shinichi, Kobayashi, Shuzo, Yamaguchi, Hiroki, Nagata, Yasunobu, Wakita, Satoshi, Nito, Chikako, Iwasaki, Yu-Ki, Murayama, Shigeo, Yoshimori, Kozo, Miki, Yoshio, Obata, Daisuke, Higashiyama, Masahiko, Masumoto, Akihide, Koga, Yoshinobu, Koretsune, Yukihiro, Aihara, Makoto, Sakata, Rei, Kashiwagi, Kenji, Mabuchi, Fumihiko, Kawase, Kazuhide, Iwata, Takeshi, Tsujikawa, Motokazu, Nishiguchi, Koji M., Akiyama, Masato, Tamiya, Gen, Fujiwara, Kohta, Shiga, Yukihiro, Yokoyama, Yu, Hashimoto, Kazuki, Sato, Masataka, Sato, Kota, Narita, Akira, Hashimoto, Sawako, Ueda, Emi, Furuta, Yoshihiko, Hata, Jun, Miyake, Masahiro, Ikeda, Hanako O., Suda, Kenji, Numa, Shogo, Mori, Yuki, Morino, Kazuya, Murakami, Yusuke, Shimokawa, Sakurako, Nakamura, Shun, Yawata, Nobuyo, Fujisawa, Kimihiko, Yamana, Satoshi, Mori, Kenichiro, Ikeda, Yasuhiro, Miyata, Kazunori, Mori, Keisuke, Ogino, Ken, Koyanagi, Yoshito, Kamatani, Yoichiro, Ninomiya, Toshiharu, Sonoda, Koh-Hei, and Nakazawa, Toru

Published
2024
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13. A multi-layer functional genomic analysis to understand noncoding genetic variation in lipids

Author

Ramdas, Shweta, Judd, Jonathan, Graham, Sarah E, Kanoni, Stavroula, Wang, Yuxuan, Surakka, Ida, Wenz, Brandon, Clarke, Shoa L, Chesi, Alessandra, Wells, Andrew, Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W, Locke, Adam E, Marouli, Eirini, Zajac, Greg JM, Wu, Kuan-Han H, Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T, Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F, Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M, Rasheed, Humaira, Havulinna, Aki S, Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A, Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J, Narita, Akira, Takayama, Jun, Martin, Hilary C, Hunt, Karen A, Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E, Campbell, Archie, Lin, Kuang, Millwood, Iona Y, Rasheed, Asif, Hindy, George, Faul, Jessica D, Zhao, Wei, Weir, David R, Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, 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, Wood, Andrew R, Ji, Yingji, Gao, Zishan, Haworth, Simon, Mitchell, Ruth E, Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A, Yao, Jie, Manichaikul, Ani, Lee, Wen-Jane, Hsiung, Chao Agnes, Warren, Helen R, Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L, Goel, Anuj, and Sabater-Lleal, Maria

Subjects
Human Genome, Biotechnology, Genetics, 2.1 Biological and endogenous factors, Aetiology, Chromatin, Genome-Wide Association Study, Genomics, Humans, Lipids, Polymorphism, Single Nucleotide, Million Veterans Program, Global Lipids Genetics Consortium, complex traits, fine-mapping, functional genomics, lipid biology, post-GWAS, regulatory mechanism, variant prioritization, Biological Sciences, Medical and Health Sciences, Genetics & Heredity
Abstract

A major challenge of genome-wide association studies (GWASs) is to translate phenotypic associations into biological insights. Here, we integrate a large GWAS on blood lipids involving 1.6 million individuals from five ancestries with a wide array of functional genomic datasets to discover regulatory mechanisms underlying lipid associations. We first prioritize lipid-associated genes with expression quantitative trait locus (eQTL) colocalizations and then add chromatin interaction data to narrow the search for functional genes. Polygenic enrichment analysis across 697 annotations from a host of tissues and cell types confirms the central role of the liver in lipid levels and highlights the selective enrichment of adipose-specific chromatin marks in high-density lipoprotein cholesterol and triglycerides. Overlapping transcription factor (TF) binding sites with lipid-associated loci identifies TFs relevant in lipid biology. In addition, we present an integrative framework to prioritize causal variants at GWAS loci, producing a comprehensive list of candidate causal genes and variants with multiple layers of functional evidence. We highlight two of the prioritized genes, CREBRF and RRBP1, which show convergent evidence across functional datasets supporting their roles in lipid biology.

Published
2022

15. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation

Author

Mahajan, Anubha, Spracklen, Cassandra N, Zhang, Weihua, Ng, Maggie CY, Petty, Lauren E, Kitajima, Hidetoshi, Yu, Grace Z, Rüeger, Sina, Speidel, Leo, Kim, Young Jin, Horikoshi, Momoko, Mercader, Josep M, Taliun, Daniel, Moon, Sanghoon, Kwak, Soo-Heon, Robertson, Neil R, Rayner, Nigel W, Loh, Marie, Kim, Bong-Jo, Chiou, Joshua, Miguel-Escalada, Irene, della Briotta Parolo, Pietro, Lin, Kuang, Bragg, Fiona, Preuss, Michael H, Takeuchi, Fumihiko, Nano, Jana, Guo, Xiuqing, Lamri, Amel, Nakatochi, Masahiro, Scott, Robert A, Lee, Jung-Jin, Huerta-Chagoya, Alicia, Graff, Mariaelisa, Chai, Jin-Fang, Parra, Esteban J, Yao, Jie, Bielak, Lawrence F, Tabara, Yasuharu, Hai, Yang, Steinthorsdottir, Valgerdur, Cook, James P, Kals, Mart, Grarup, Niels, Schmidt, Ellen M, Pan, Ian, Sofer, Tamar, Wuttke, Matthias, Sarnowski, Chloe, Gieger, Christian, Nousome, Darryl, Trompet, Stella, Long, Jirong, Sun, Meng, Tong, Lin, Chen, Wei-Min, Ahmad, Meraj, Noordam, Raymond, Lim, Victor JY, Tam, Claudia HT, Joo, Yoonjung Yoonie, Chen, Chien-Hsiun, Raffield, Laura M, Lecoeur, Cécile, Prins, Bram Peter, Nicolas, Aude, Yanek, Lisa R, Chen, Guanjie, Jensen, Richard A, Tajuddin, Salman, Kabagambe, Edmond K, An, Ping, Xiang, Anny H, Choi, Hyeok Sun, Cade, Brian E, Tan, Jingyi, Flanagan, Jack, Abaitua, Fernando, Adair, Linda S, Adeyemo, Adebowale, Aguilar-Salinas, Carlos A, Akiyama, Masato, Anand, Sonia S, Bertoni, Alain, Bian, Zheng, Bork-Jensen, Jette, Brandslund, Ivan, Brody, Jennifer A, Brummett, Chad M, Buchanan, Thomas A, Canouil, Mickaël, Chan, Juliana CN, Chang, Li-Ching, Chee, Miao-Li, Chen, Ji, Chen, Shyh-Huei, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, and Cushman, Mary

Subjects
Genetics, Diabetes, Human Genome, Metabolic and endocrine, Diabetes Mellitus, Type 2, Ethnicity, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Polymorphism, Single Nucleotide, Risk Factors, FinnGen, eMERGE Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P 50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.

Published
2022

16. Large-scale multitrait genome-wide association analyses identify hundreds of glaucoma risk loci

Author

Han, Xikun, Gharahkhani, Puya, Hamel, Andrew R., Ong, Jue Sheng, Rentería, Miguel E., Mehta, Puja, Dong, Xianjun, Pasutto, Francesca, Hammond, Christopher, Young, Terri L., Hysi, Pirro, Lotery, Andrew J., Jorgenson, Eric, Choquet, Hélène, Hauser, Michael, Cooke Bailey, Jessica N., Nakazawa, Toru, Akiyama, Masato, Shiga, Yukihiro, Fuller, Zachary L., Wang, Xin, Hewitt, Alex W., Craig, Jamie E., Pasquale, Louis R., Mackey, David A., Wiggs, Janey L., Khawaja, Anthony P., Segrè, Ayellet V., and MacGregor, Stuart

Published
2023
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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, and Sattar, Naveed

Subjects
Heart Disease, Prevention, Human Genome, Genetics, Cardiovascular, 2.1 Biological and endogenous factors, Aetiology, Good Health and Well Being, Cardiovascular Diseases, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Linkage Disequilibrium, Multifactorial Inheritance, Polymorphism, Single Nucleotide, Population Groups, VA Million Veteran Program, Global Lipids Genetics Consortium*, General Science & Technology
Abstract

Increased blood lipid levels are heritable risk factors of cardiovascular disease with varied prevalence worldwide owing to different dietary patterns and medication use1. Despite advances in prevention and treatment, in particular through reducing low-density lipoprotein cholesterol levels2, heart disease remains the leading cause of death worldwide3. 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 GWAS4-23 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 patterns24. 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 medicine25, we anticipate that increased diversity of participants will lead to more accurate and equitable26 application of polygenic scores in clinical practice.

Published
2021

20. Genome-wide meta-analysis identifies 127 open-angle glaucoma loci with consistent effect across ancestries.

Author

Gharahkhani, Puya, Jorgenson, Eric, Hysi, Pirro, Khawaja, Anthony P, Pendergrass, Sarah, Han, Xikun, Ong, Jue Sheng, Hewitt, Alex W, Segrè, Ayellet V, Rouhana, John M, Hamel, Andrew R, Igo, Robert P, Choquet, Helene, Qassim, Ayub, Josyula, Navya S, Cooke Bailey, Jessica N, Bonnemaijer, Pieter WM, Iglesias, Adriana, Siggs, Owen M, Young, Terri L, Vitart, Veronique, Thiadens, Alberta AHJ, Karjalainen, Juha, Uebe, Steffen, Melles, Ronald B, Nair, K Saidas, Luben, Robert, Simcoe, Mark, Amersinghe, Nishani, Cree, Angela J, Hohn, Rene, Poplawski, Alicia, Chen, Li Jia, Rong, Shi-Song, Aung, Tin, Vithana, Eranga Nishanthie, NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, 23 and Me Research Team, Tamiya, Gen, Shiga, Yukihiro, Yamamoto, Masayuki, Nakazawa, Toru, Currant, Hannah, Birney, Ewan, Wang, Xin, Auton, Adam, Lupton, Michelle K, Martin, Nicholas G, Ashaye, Adeyinka, Olawoye, Olusola, Williams, Susan E, Akafo, Stephen, Ramsay, Michele, Hashimoto, Kazuki, Kamatani, Yoichiro, Akiyama, Masato, Momozawa, Yukihide, Foster, Paul J, Khaw, Peng T, Morgan, James E, Strouthidis, Nicholas G, Kraft, Peter, Kang, Jae H, Pang, Chi Pui, Pasutto, Francesca, Mitchell, Paul, Lotery, Andrew J, Palotie, Aarno, van Duijn, Cornelia, Haines, Jonathan L, Hammond, Chris, Pasquale, Louis R, Klaver, Caroline CW, Hauser, Michael, Khor, Chiea Chuen, Mackey, David A, Kubo, Michiaki, Cheng, Ching-Yu, Craig, Jamie E, MacGregor, Stuart, and Wiggs, Janey L

Subjects
NEIGHBORHOOD consortium, ANZRAG consortium, Biobank Japan project, FinnGen study, UK Biobank Eye and Vision Consortium, GIGA study group, and Me Research Team, Humans, Glaucoma, Open-Angle, Genetic Predisposition to Disease, Genotype, Polymorphism, Single Nucleotide, Asian Continental Ancestry Group, European Continental Ancestry Group, Genome-Wide Association Study, Genetic Loci, Glaucoma, Open-Angle, Polymorphism, Single Nucleotide
Abstract

Primary open-angle glaucoma (POAG), is a heritable common cause of blindness world-wide. To identify risk loci, we conduct a large multi-ethnic meta-analysis of genome-wide association studies on a total of 34,179 cases and 349,321 controls, identifying 44 previously unreported risk loci and confirming 83 loci that were previously known. The majority of loci have broadly consistent effects across European, Asian and African ancestries. Cross-ancestry data improve fine-mapping of causal variants for several loci. Integration of multiple lines of genetic evidence support the functional relevance of the identified POAG risk loci and highlight potential contributions of several genes to POAG pathogenesis, including SVEP1, RERE, VCAM1, ZNF638, CLIC5, SLC2A12, YAP1, MXRA5, and SMAD6. Several drug compounds targeting POAG risk genes may be potential glaucoma therapeutic candidates.

Published
2021

21. Cross-ancestry genome-wide analysis of atrial fibrillation unveils disease biology and enables cardioembolic risk prediction

Author

Miyazawa, Kazuo, Ito, Kaoru, Ito, Masamichi, Zou, Zhaonan, Kubota, Masayuki, Nomura, Seitaro, Matsunaga, Hiroshi, Koyama, Satoshi, Ieki, Hirotaka, Akiyama, Masato, Koike, Yoshinao, Kurosawa, Ryo, Yoshida, Hiroki, Ozaki, Kouichi, Onouchi, Yoshihiro, Takahashi, Atsushi, Matsuda, Koichi, Murakami, Yoshinori, Aburatani, Hiroyuki, Kubo, Michiaki, Momozawa, Yukihide, Terao, Chikashi, Oki, Shinya, Akazawa, Hiroshi, Kamatani, Yoichiro, and Komuro, Issei

Published
2023
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22. Genome-wide association study of intracranial aneurysms identifies 17 risk loci and genetic overlap with clinical risk factors

Author

Bakker, Mark K, van der Spek, Rick AA, van Rheenen, Wouter, Morel, Sandrine, Bourcier, Romain, Hostettler, Isabel C, Alg, Varinder S, van Eijk, Kristel R, Koido, Masaru, Akiyama, Masato, Terao, Chikashi, Matsuda, Koichi, Walters, Robin G, Lin, Kuang, Li, Liming, Millwood, Iona Y, Chen, Zhengming, Rouleau, Guy A, Zhou, Sirui, Rannikmäe, Kristiina, Sudlow, Cathie LM, Houlden, Henry, van den Berg, Leonard H, Dina, Christian, Naggara, Olivier, Gentric, Jean-Christophe, Shotar, Eimad, Eugène, François, Desal, Hubert, Winsvold, Bendik S, Børte, Sigrid, Johnsen, Marianne Bakke, Brumpton, Ben M, Sandvei, Marie Søfteland, Willer, Cristen J, Hveem, Kristian, Zwart, John-Anker, Verschuren, WM Monique, Friedrich, Christoph M, Hirsch, Sven, Schilling, Sabine, Dauvillier, Jérôme, Martin, Olivier, Jones, Gregory T, Bown, Matthew J, Ko, Nerissa U, Kim, Helen, Coleman, Jonathan RI, Breen, Gerome, Zaroff, Jonathan G, Klijn, Catharina JM, Malik, Rainer, Dichgans, Martin, Sargurupremraj, Muralidharan, Tatlisumak, Turgut, Amouyel, Philippe, Debette, Stéphanie, Rinkel, Gabriel JE, Worrall, Bradford B, Pera, Joanna, Slowik, Agnieszka, Gaál-Paavola, Emília I, Niemelä, Mika, Jääskeläinen, Juha E, von Und Zu Fraunberg, Mikael, Lindgren, Antti, Broderick, Joseph P, Werring, David J, Woo, Daniel, Redon, Richard, Bijlenga, Philippe, Kamatani, Yoichiro, Veldink, Jan H, and Ruigrok, Ynte M

Subjects
Genetics, Brain Disorders, Human Genome, Clinical Research, Prevention, Stroke, Neurosciences, Aetiology, 2.1 Biological and endogenous factors, Cardiovascular, Asian People, Blood Pressure, Case-Control Studies, Endothelial Cells, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Hypertension, Intracranial Aneurysm, Polymorphism, Single Nucleotide, Risk Factors, Smoking, Subarachnoid Hemorrhage, White People, HUNT All-In Stroke, China Kadoorie Biobank Collaborative Group, BioBank Japan Project Consortium, ICAN Study Group, CADISP Group, Genetics and Observational Subarachnoid Haemorrhage (GOSH) Study investigators, International Stroke Genetics Consortium, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Rupture of an intracranial aneurysm leads to subarachnoid hemorrhage, a severe type of stroke. To discover new risk loci and the genetic architecture of intracranial aneurysms, we performed a cross-ancestry, genome-wide association study in 10,754 cases and 306,882 controls of European and East Asian ancestry. We discovered 17 risk loci, 11 of which are new. We reveal a polygenic architecture and explain over half of the disease heritability. We show a high genetic correlation between ruptured and unruptured intracranial aneurysms. We also find a suggestive role for endothelial cells by using gene mapping and heritability enrichment. Drug-target enrichment shows pleiotropy between intracranial aneurysms and antiepileptic and sex hormone drugs, providing insights into intracranial aneurysm pathophysiology. Finally, genetic risks for smoking and high blood pressure, the two main clinical risk factors, play important roles in intracranial aneurysm risk, and drive most of the genetic correlation between intracranial aneurysms and other cerebrovascular traits.

Published
2020

23. Trans-ethnic and Ancestry-Specific Blood-Cell Genetics in 746,667 Individuals from 5 Global Populations

Author

Chen, Ming-Huei, Raffield, Laura M, Mousas, Abdou, Sakaue, Saori, Huffman, Jennifer E, Moscati, Arden, Trivedi, Bhavi, Jiang, Tao, Akbari, Parsa, Vuckovic, Dragana, Bao, Erik L, Zhong, Xue, Manansala, Regina, Laplante, Véronique, Chen, Minhui, Lo, Ken Sin, Qian, Huijun, Lareau, Caleb A, Beaudoin, Mélissa, Hunt, Karen A, Akiyama, Masato, Bartz, Traci M, Ben-Shlomo, Yoav, Beswick, Andrew, Bork-Jensen, Jette, Bottinger, Erwin P, Brody, Jennifer A, van Rooij, Frank JA, Chitrala, Kumaraswamynaidu, Cho, Kelly, Choquet, Hélène, Correa, Adolfo, Danesh, John, Di Angelantonio, Emanuele, Dimou, Niki, Ding, Jingzhong, Elliott, Paul, Esko, Tõnu, Evans, Michele K, Floyd, James S, Broer, Linda, Grarup, Niels, Guo, Michael H, Greinacher, Andreas, Haessler, Jeff, Hansen, Torben, Howson, Joanna MM, Huang, Qin Qin, Huang, Wei, Jorgenson, Eric, Kacprowski, Tim, Kähönen, Mika, Kamatani, Yoichiro, Kanai, Masahiro, Karthikeyan, Savita, Koskeridis, Fotis, Lange, Leslie A, Lehtimäki, Terho, Lerch, Markus M, Linneberg, Allan, Liu, Yongmei, Lyytikäinen, Leo-Pekka, Manichaikul, Ani, Martin, Hilary C, Matsuda, Koichi, Mohlke, Karen L, Mononen, Nina, Murakami, Yoshinori, Nadkarni, Girish N, Nauck, Matthias, Nikus, Kjell, Ouwehand, Willem H, Pankratz, Nathan, Pedersen, Oluf, Preuss, Michael, Psaty, Bruce M, Raitakari, Olli T, Roberts, David J, Rich, Stephen S, Rodriguez, Benjamin AT, Rosen, Jonathan D, Rotter, Jerome I, Schubert, Petra, Spracklen, Cassandra N, Surendran, Praveen, Tang, Hua, Tardif, Jean-Claude, Trembath, Richard C, Ghanbari, Mohsen, Völker, Uwe, Völzke, Henry, Watkins, Nicholas A, Zonderman, Alan B, Program, VA Million Veteran, Wilson, Peter WF, Li, Yun, Butterworth, Adam S, Gauchat, Jean-François, Chiang, Charleston WK, and Li, Bingshan

Subjects
Genetics, Good Health and Well Being, Asian People, Genome-Wide Association Study, HEK293 Cells, Humans, Interleukin-7, Mutation, Missense, Phenotype, Polymorphism, Single Nucleotide, White People, VA Million Veteran Program, interleukin-7, genetic architecture, fine-mapping, selective sweeps, polygenic trait score, phenome-wide association study, Biological Sciences, Medical and Health Sciences, Developmental Biology
Abstract

Most loci identified by GWASs have been found in populations of European ancestry (EUR). In trans-ethnic meta-analyses for 15 hematological traits in 746,667 participants, including 184,535 non-EUR individuals, we identified 5,552 trait-variant associations at p < 5 × 10-9, including 71 novel associations not found in EUR populations. We also identified 28 additional novel variants in ancestry-specific, non-EUR meta-analyses, including an IL7 missense variant in South Asians associated with lymphocyte count in vivo and IL-7 secretion levels in vitro. Fine-mapping prioritized variants annotated as functional and generated 95% credible sets that were 30% smaller when using the trans-ethnic as opposed to the EUR-only results. We explored the clinical significance and predictive value of trans-ethnic variants in multiple populations and compared genetic architecture and the effect of natural selection on these blood phenotypes between populations. Altogether, our results for hematological traits highlight the value of a more global representation of populations in genetic studies.

Published
2020

24. Identification of type 2 diabetes loci in 433,540 East Asian individuals

Author

Spracklen, Cassandra N, Horikoshi, Momoko, Kim, Young Jin, Lin, Kuang, Bragg, Fiona, Moon, Sanghoon, Suzuki, Ken, Tam, Claudia HT, Tabara, Yasuharu, Kwak, Soo-Heon, Takeuchi, Fumihiko, Long, Jirong, Lim, Victor JY, Chai, Jin-Fang, Chen, Chien-Hsiun, Nakatochi, Masahiro, Yao, Jie, Choi, Hyeok Sun, Iyengar, Apoorva K, Perrin, Hannah J, Brotman, Sarah M, van de Bunt, Martijn, Gloyn, Anna L, Below, Jennifer E, Boehnke, Michael, Bowden, Donald W, Chambers, John C, Mahajan, Anubha, McCarthy, Mark I, Ng, Maggie CY, Petty, Lauren E, Zhang, Weihua, Morris, Andrew P, Adair, Linda S, Akiyama, Masato, Bian, Zheng, Chan, Juliana CN, Chang, Li-Ching, Chee, Miao-Li, Chen, Yii-Der Ida, Chen, Yuan-Tsong, Chen, Zhengming, Chuang, Lee-Ming, Du, Shufa, Gordon-Larsen, Penny, Gross, Myron, Guo, Xiuqing, Guo, Yu, Han, Sohee, Howard, Annie-Green, Huang, Wei, Hung, Yi-Jen, Hwang, Mi Yeong, Hwu, Chii-Min, Ichihara, Sahoko, Isono, Masato, Jang, Hye-Mi, Jiang, Guozhi, Jonas, Jost B, Kamatani, Yoichiro, Katsuya, Tomohiro, Kawaguchi, Takahisa, Khor, Chiea-Chuen, Kohara, Katsuhiko, Lee, Myung-Shik, Lee, Nanette R, Li, Liming, Liu, Jianjun, Luk, Andrea O, Lv, Jun, Okada, Yukinori, Pereira, Mark A, Sabanayagam, Charumathi, Shi, Jinxiu, Shin, Dong Mun, So, Wing Yee, Takahashi, Atsushi, Tomlinson, Brian, Tsai, Fuu-Jen, van Dam, Rob M, Xiang, Yong-Bing, Yamamoto, Ken, Yamauchi, Toshimasa, Yoon, Kyungheon, Yu, Canqing, Yuan, Jian-Min, Zhang, Liang, Zheng, Wei, Igase, Michiya, Cho, Yoon Shin, Rotter, Jerome I, Wang, Ya-Xing, Sheu, Wayne HH, Yokota, Mitsuhiro, Wu, Jer-Yuarn, Cheng, Ching-Yu, Wong, Tien-Yin, Shu, Xiao-Ou, Kato, Norihiro, and Park, Kyong-Soo

Subjects
Human Genome, Diabetes, Biotechnology, Genetics, Aetiology, 2.1 Biological and endogenous factors, Metabolic and endocrine, Aldehyde Dehydrogenase, Mitochondrial, Alleles, Ankyrins, Asian People, Body Mass Index, Case-Control Studies, Diabetes Mellitus, Type 2, Europe, Eye Proteins, Asia, Eastern, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Homeodomain Proteins, Humans, Male, Nerve Tissue Proteins, RNA, Messenger, Transcription Factors, Transcription, Genetic, General Science & Technology
Abstract

Meta-analyses of genome-wide association studies (GWAS) have identified more than 240 loci that are associated with type 2 diabetes (T2D)1,2; however, most of these loci have been identified in analyses of individuals with European ancestry. Here, to examine T2D risk in East Asian individuals, we carried out a meta-analysis of GWAS data from 77,418 individuals with T2D and 356,122 healthy control individuals. In the main analysis, we identified 301 distinct association signals at 183 loci, and across T2D association models with and without consideration of body mass index and sex, we identified 61 loci that are newly implicated in predisposition to T2D. Common variants associated with T2D in both East Asian and European populations exhibited strongly correlated effect sizes. Previously undescribed associations include signals in or near GDAP1, PTF1A, SIX3, ALDH2, a microRNA cluster, and genes that affect the differentiation of muscle and adipose cells3. At another locus, expression quantitative trait loci at two overlapping T2D signals affect two genes-NKX6-3 and ANK1-in different tissues4-6. Association studies in diverse populations identify additional loci and elucidate disease-associated genes, biology, and pathways.

Published
2020

25. CKD, Brain Atrophy, and White Matter Lesion Volume: The Japan Prospective Studies Collaboration for Aging and Dementia

Author

Ninomiya, Toshiharu, Hata, Jun, Shibata, Mao, Honda, Takanori, Ohara, Tomoyuki, Akiyama, Masato, Nakaji, Shigeyuki, Murashita, Koichi, Mikami, Tatsuya, Jung, Songee, Misawa, Mina, Maeda, Tetsuya, Ishizuka, Naoki, Akasaka, Hiroshi, Terayama, Yasuo, Yonezawa, Hisashi, Takahashi, Junko, Ono, Kenjiro, Noguchi-Shinohara, Moeko, Komatsu, Junji, Shibata, Shutaro, Yuki-Nozaki, Sohshi, Mimura, Masaru, Bun, Shogyoku, Niimura, Hidehito, Shikimoto, Ryo, Kida, Hisashi, Nakashima, Kenji, Fukada, Yasuyo, Kowa, Hisanori, Nakano, Toshiya, Wada, Kenji, Kishi, Masafumi, Ozaki, Tomoki, Tachibana, Ayumi, Yoshino, Yuta, Shu-ichi Ueno, Jun-ichi Iga, Takebayashi, Minoru, Ishikawa, Tomohisa, Yuki, Seiji, Koyama, Asuka, Kajitani, Naoto, Hashimoto, Mamoru, Ikeda, Manabu, Kokubo, Yoshihiro, Uchida, Kazuhiro, Esaki, Midori, Taki, Yasuyuki, Tatewaki, Yasuko, Thyreau, Benjamin, Yonemoto, Koji, Yoshida, Hisako, Muto, Kaori, Inoue, Yusuke, Ri, Izen, Momozawa, Yukihide, Terao, Chikashi, Kubo, Michiaki, Kiyohara, Yutaka, Maki, Kenji, Hirabayashi, Naoki, Sakata, Satoko, Furuta, Yoshihiko, Yamasaki, Keisuke, Kitazono, Takanari, and Iga, Jun-ichi

Published
2023
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28. Associations of autozygosity with a broad range of human phenotypes.

Author

Clark, David W, Okada, Yukinori, Moore, Kristjan HS, Mason, Dan, Pirastu, Nicola, Gandin, Ilaria, Mattsson, Hannele, Barnes, Catriona LK, Lin, Kuang, Zhao, Jing Hua, Deelen, Patrick, Rohde, Rebecca, Schurmann, Claudia, Guo, Xiuqing, Giulianini, Franco, Zhang, Weihua, Medina-Gomez, Carolina, Karlsson, Robert, Bao, Yanchun, Bartz, Traci M, Baumbach, Clemens, Biino, Ginevra, Bixley, Matthew J, Brumat, Marco, Chai, Jin-Fang, Corre, Tanguy, Cousminer, Diana L, Dekker, Annelot M, Eccles, David A, van Eijk, Kristel R, Fuchsberger, Christian, Gao, He, Germain, Marine, Gordon, Scott D, de Haan, Hugoline G, Harris, Sarah E, Hofer, Edith, Huerta-Chagoya, Alicia, Igartua, Catherine, Jansen, Iris E, Jia, Yucheng, Kacprowski, Tim, Karlsson, Torgny, Kleber, Marcus E, Li, Shengchao Alfred, Li-Gao, Ruifang, Mahajan, Anubha, Matsuda, Koichi, Meidtner, Karina, Meng, Weihua, Montasser, May E, van der Most, Peter J, Munz, Matthias, Nutile, Teresa, Palviainen, Teemu, Prasad, Gauri, Prasad, Rashmi B, Priyanka, Tallapragada Divya Sri, Rizzi, Federica, Salvi, Erika, Sapkota, Bishwa R, Shriner, Daniel, Skotte, Line, Smart, Melissa C, Smith, Albert Vernon, van der Spek, Ashley, Spracklen, Cassandra N, Strawbridge, Rona J, Tajuddin, Salman M, Trompet, Stella, Turman, Constance, Verweij, Niek, Viberti, Clara, Wang, Lihua, Warren, Helen R, Wootton, Robyn E, Yanek, Lisa R, Yao, Jie, Yousri, Noha A, Zhao, Wei, Adeyemo, Adebowale A, Afaq, Saima, Aguilar-Salinas, Carlos Alberto, Akiyama, Masato, Albert, Matthew L, Allison, Matthew A, Alver, Maris, Aung, Tin, Azizi, Fereidoun, Bentley, Amy R, Boeing, Heiner, Boerwinkle, Eric, Borja, Judith B, de Borst, Gert J, Bottinger, Erwin P, Broer, Linda, Campbell, Harry, Chanock, Stephen, Chee, Miao-Li, and Chen, Guanjie

Subjects
Humans, Body Size, Risk-Taking, Cognition, Health Status, Consanguinity, Fertility, Haplotypes, Homozygote, Alleles, Inbreeding Depression
Abstract

In many species, the offspring of related parents suffer reduced reproductive success, a phenomenon known as inbreeding depression. In humans, the importance of this effect has remained unclear, partly because reproduction between close relatives is both rare and frequently associated with confounding social factors. Here, using genomic inbreeding coefficients (FROH) for >1.4 million individuals, we show that FROH is significantly associated (p

Published
2019

29. Discerning asthma endotypes through comorbidity mapping

Author

Jia, Gengjie, Zhong, Xue, Im, Hae Kyung, Schoettler, Nathan, Pividori, Milton, Hogarth, D. Kyle, Sperling, Anne I., White, Steven R., Naureckas, Edward T., Lyttle, Christopher S., Terao, Chikashi, Kamatani, Yoichiro, Akiyama, Masato, Matsuda, Koichi, Kubo, Michiaki, Cox, Nancy J., Ober, Carole, Rzhetsky, Andrey, and Solway, Julian

Published
2022
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30. Differential and shared genetic effects on kidney function between diabetic and non-diabetic individuals

Author

Winkler, Thomas W., Rasheed, Humaira, Teumer, Alexander, Gorski, Mathias, Rowan, Bryce X., Stanzick, Kira J., Thomas, Laurent F., Tin, Adrienne, Hoppmann, Anselm, Chu, Audrey Y., Tayo, Bamidele, Thio, Chris H. L., Cusi, Daniele, Chai, Jin-Fang, Sieber, Karsten B., Horn, Katrin, Li, Man, Scholz, Markus, Cocca, Massimiliano, Wuttke, Matthias, van der Most, Peter J., Yang, Qiong, Ghasemi, Sahar, Nutile, Teresa, Li, Yong, Pontali, Giulia, Günther, Felix, Dehghan, Abbas, Correa, Adolfo, Parsa, Afshin, Feresin, Agnese, de Vries, Aiko P. J., Zonderman, Alan B., Smith, Albert V., Oldehinkel, Albertine J., De Grandi, Alessandro, Rosenkranz, Alexander R., Franke, Andre, Teren, Andrej, Metspalu, Andres, Hicks, Andrew A., Morris, Andrew P., Tönjes, Anke, Morgan, Anna, Podgornaia, Anna I., Peters, Annette, Körner, Antje, Mahajan, Anubha, Campbell, Archie, Freedman, Barry I., Spedicati, Beatrice, Ponte, Belen, Schöttker, Ben, Brumpton, Ben, Banas, Bernhard, Krämer, Bernhard K., Jung, Bettina, Åsvold, Bjørn Olav, Smith, Blair H., Ning, Boting, Penninx, Brenda W. J. H., Vanderwerff, Brett R., Psaty, Bruce M., Kammerer, Candace M., Langefeld, Carl D., Hayward, Caroline, Spracklen, Cassandra N., Robinson-Cohen, Cassianne, Hartman, Catharina A., Lindgren, Cecilia M., Wang, Chaolong, Sabanayagam, Charumathi, Heng, Chew-Kiat, Lanzani, Chiara, Khor, Chiea-Chuen, Cheng, Ching-Yu, Fuchsberger, Christian, Gieger, Christian, Shaffer, Christian M., Schulz, Christina-Alexandra, Willer, Cristen J., Chasman, Daniel I., Gudbjartsson, Daniel F., Ruggiero, Daniela, Toniolo, Daniela, Czamara, Darina, Porteous, David J., Waterworth, Dawn M., Mascalzoni, Deborah, Mook-Kanamori, Dennis O., Reilly, Dermot F., Daw, E. Warwick, Hofer, Edith, Boerwinkle, Eric, Salvi, Erika, Bottinger, Erwin P., Tai, E-Shyong, Catamo, Eulalia, Rizzi, Federica, Guo, Feng, Rivadeneira, Fernando, Guilianini, Franco, Sveinbjornsson, Gardar, Ehret, Georg, Waeber, Gerard, Biino, Ginevra, Girotto, Giorgia, Pistis, Giorgio, Nadkarni, Girish N., Delgado, Graciela E., Montgomery, Grant W., Snieder, Harold, Campbell, Harry, White, Harvey D., Gao, He, Stringham, Heather M., Schmidt, Helena, Li, Hengtong, Brenner, Hermann, Holm, Hilma, Kirsten, Holgen, Kramer, Holly, Rudan, Igor, Nolte, Ilja M., Tzoulaki, Ioanna, Olafsson, Isleifur, Martins, Jade, Cook, James P., Wilson, James F., Halbritter, Jan, Felix, Janine F., Divers, Jasmin, Kooner, Jaspal S., Lee, Jeannette Jen-Mai, O’Connell, Jeffrey, Rotter, Jerome I., Liu, Jianjun, Xu, Jie, Thiery, Joachim, Ärnlöv, Johan, Kuusisto, Johanna, Jakobsdottir, Johanna, Tremblay, Johanne, Chambers, John C., Whitfield, John B., Gaziano, John M., Marten, Jonathan, Coresh, Josef, Jonas, Jost B., Mychaleckyj, Josyf C., Christensen, Kaare, Eckardt, Kai-Uwe, Mohlke, Karen L., Endlich, Karlhans, Dittrich, Katalin, Ryan, Kathleen A., Rice, Kenneth M., Taylor, Kent D., Ho, Kevin, Nikus, Kjell, Matsuda, Koichi, Strauch, Konstantin, Miliku, Kozeta, Hveem, Kristian, Lind, Lars, Wallentin, Lars, Yerges-Armstrong, Laura M., Raffield, Laura M., Phillips, Lawrence S., Launer, Lenore J., Lyytikäinen, Leo-Pekka, Lange, Leslie A., Citterio, Lorena, Klaric, Lucija, Ikram, M. Arfan, Ising, Marcus, Kleber, Marcus E., Francescatto, Margherita, Concas, Maria Pina, Ciullo, Marina, Piratsu, Mario, Orho-Melander, Marju, Laakso, Markku, Loeffler, Markus, Perola, Markus, de Borst, Martin H., Gögele, Martin, Bianca, Martina La, Lukas, Mary Ann, Feitosa, Mary F., Biggs, Mary L., Wojczynski, Mary K., Kavousi, Maryam, Kanai, Masahiro, Akiyama, Masato, Yasuda, Masayuki, Nauck, Matthias, Waldenberger, Melanie, Chee, Miao-Li, Chee, Miao-Ling, Boehnke, Michael, Preuss, Michael H., Stumvoll, Michael, Province, Michael A., Evans, Michele K., O’Donoghue, Michelle L., Kubo, Michiaki, Kähönen, Mika, Kastarinen, Mika, Nalls, Mike A., Kuokkanen, Mikko, Ghanbari, Mohsen, Bochud, Murielle, Josyula, Navya Shilpa, Martin, Nicholas G., Tan, Nicholas Y. Q., Palmer, Nicholette D., Pirastu, Nicola, Schupf, Nicole, Verweij, Niek, Hutri-Kähönen, Nina, Mononen, Nina, Bansal, Nisha, Devuyst, Olivier, Melander, Olle, Raitakari, Olli T., Polasek, Ozren, Manunta, Paolo, Gasparini, Paolo, Mishra, Pashupati P., Sulem, Patrick, Magnusson, Patrik K. E., Elliott, Paul, Ridker, Paul M., Hamet, Pavel, Svensson, Per O., Joshi, Peter K., Kovacs, Peter, Pramstaller, Peter P., Rossing, Peter, Vollenweider, Peter, van der Harst, Pim, Dorajoo, Rajkumar, Sim, Ralene Z. H., Burkhardt, Ralph, Tao, Ran, Noordam, Raymond, Mägi, Reedik, Schmidt, Reinhold, de Mutsert, Renée, Rueedi, Rico, van Dam, Rob M., Carroll, Robert J., Gansevoort, Ron T., Loos, Ruth J. F., Felicita, Sala Cinzia, Sedaghat, Sanaz, Padmanabhan, Sandosh, Freitag-Wolf, Sandra, Pendergrass, Sarah A., Graham, Sarah E., Gordon, Scott D., Hwang, Shih-Jen, Kerr, Shona M., Vaccargiu, Simona, Patil, Snehal B., Hallan, Stein, Bakker, Stephan J. L., Lim, Su-Chi, Lucae, Susanne, Vogelezang, Suzanne, Bergmann, Sven, Corre, Tanguy, Ahluwalia, Tarunveer S., Lehtimäki, Terho, Boutin, Thibaud S., Meitinger, Thomas, Wong, Tien-Yin, Bergler, Tobias, Rabelink, Ton J., Esko, Tõnu, Haller, Toomas, Thorsteinsdottir, Unnur, Völker, Uwe, Foo, Valencia Hui Xian, Salomaa, Veikko, Vitart, Veronique, Giedraitis, Vilmantas, Gudnason, Vilmundur, Jaddoe, Vincent W. V., Huang, Wei, Zhang, Weihua, Wei, Wen Bin, Kiess, Wieland, März, Winfried, Koenig, Wolfgang, Lieb, Wolfgang, Gao, Xin, Sim, Xueling, Wang, Ya Xing, Friedlander, Yechiel, Tham, Yih-Chung, Kamatani, Yoichiro, Okada, Yukinori, Milaneschi, Yuri, Yu, Zhi, Stark, Klaus J., Stefansson, Kari, Böger, Carsten A., Hung, Adriana M., Kronenberg, Florian, Köttgen, Anna, Pattaro, Cristian, and Heid, Iris M.

Published
2022
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31. Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis

Author

Kanoni, Stavroula, Graham, Sarah E., Wang, Yuxuan, Surakka, Ida, Ramdas, Shweta, Zhu, Xiang, Clarke, Shoa L., Bhatti, Konain Fatima, Vedantam, Sailaja, Winkler, Thomas W., Locke, Adam E., Marouli, Eirini, Zajac, Greg J. M., Wu, Kuan-Han H., Ntalla, Ioanna, Hui, Qin, Klarin, Derek, Hilliard, Austin T., Wang, Zeyuan, Xue, Chao, Thorleifsson, Gudmar, Helgadottir, Anna, Gudbjartsson, Daniel F., Holm, Hilma, Olafsson, Isleifur, Hwang, Mi Yeong, Han, Sohee, Akiyama, Masato, Sakaue, Saori, Terao, Chikashi, Kanai, Masahiro, Zhou, Wei, Brumpton, Ben M., Rasheed, Humaira, Havulinna, Aki S., Veturi, Yogasudha, Pacheco, Jennifer Allen, Rosenthal, Elisabeth A., Lingren, Todd, Feng, QiPing, Kullo, Iftikhar J., Narita, Akira, Takayama, Jun, Martin, Hilary C., Hunt, Karen A., Trivedi, Bhavi, Haessler, Jeffrey, Giulianini, Franco, Bradford, Yuki, Miller, Jason E., Campbell, Archie, Lin, Kuang, Millwood, Iona Y., Rasheed, Asif, Hindy, George, Faul, Jessica D., Zhao, Wei, Weir, David R., Turman, Constance, Huang, Hongyan, Graff, Mariaelisa, Choudhury, Ananyo, Sengupta, Dhriti, 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, Wood, Andrew R., Ji, Yingji, Gao, Zishan, Haworth, Simon, Yousri, Noha A., Mitchell, Ruth E., Chai, Jin Fang, Aadahl, Mette, Bjerregaard, Anne A., Yao, Jie, Manichaikul, Ani, Hwu, Chii-Min, Hung, Yi-Jen, Warren, Helen R., Ramirez, Julia, Bork-Jensen, Jette, Kårhus, Line L., Goel, Anuj, Sabater-Lleal, Maria, Noordam, Raymond, Mauro, Pala, Matteo, Floris, McDaid, Aaron F., Marques-Vidal, Pedro, Wielscher, Matthias, Trompet, Stella, Sattar, Naveed, Møllehave, Line T., Munz, Matthias, Zeng, Lingyao, Huang, Jianfeng, Yang, Bin, Poveda, Alaitz, Kurbasic, Azra, Lamina, Claudia, Forer, Lukas, Scholz, Markus, Galesloot, Tessel E., Bradfield, Jonathan P., Ruotsalainen, Sanni E., Daw, EWarwick, Zmuda, Joseph M., Mitchell, Jonathan S., Fuchsberger, Christian, Christensen, Henry, Brody, Jennifer A., Vazquez-Moreno, Miguel, Feitosa, Mary F., Wojczynski, Mary K., Wang, Zhe, Preuss, Michael H., Mangino, Massimo, Christofidou, Paraskevi, Verweij, Niek, Benjamins, Jan W., Engmann, Jorgen, Tsao, Noah L., Verma, Anurag, 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, Demirkan, Ayşe, Leonard, Hampton L., Marten, Jonathan, Frank, Mirjam, Schmidt, Börge, 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, Nongmaithem, Suraj S., Bayyana, Swati, Stringham, Heather M., Irvin, Marguerite R., Oldmeadow, Christopher, Kim, Han-Na, Ryu, Seungho, Timmers, Paul R. H. J., Arbeeva, Liubov, Dorajoo, Rajkumar, Lange, Leslie A., 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, Chen, Shufeng, Liu, Fangchao, Yang, Jingyun, Kentistou, Katherine A., Banas, Bernhard, Nardone, Giuseppe Giovanni, Meidtner, Karina, Bielak, Lawrence F., Smith, Jennifer A., Hebbar, Prashantha, Farmaki, Aliki-Eleni, Hofer, Edith, Lin, Maoxuan, Concas, Maria Pina, Vaccargiu, Simona, van der Most, Peter J., Pitkänen, Niina, Cade, Brian E., van der Laan, Sander W., Chitrala, Kumaraswamy Naidu, Weiss, Stefan, Bentley, Amy R., Doumatey, Ayo P., Adeyemo, Adebowale A., Lee, Jong Young, Petersen, Eva R. B., Nielsen, Aneta A., 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, Hidalgo, Bertha, Giannakopoulou, Olga, Cai, Qiuyin, Obura, Morgan O., van Setten, Jessica, Li, Xiaoyin, Liang, Jingjing, Tang, Hua, Terzikhan, Natalie, Shin, Jae Hun, Jackson, Rebecca D., Reiner, Alexander P., Martin, Lisa Warsinger, Chen, Zhengming, Li, Liming, Kawaguchi, Takahisa, Thiery, Joachim, Bis, Joshua C., 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, 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 W. J., 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., Zimmermann, Martina E., 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, Bandinelli, Stefania, Dedoussis, George, Thanaraj, Thangavel Alphonse, Kardia, Sharon L. R., Peyser, Patricia A., Kato, Norihiro, Schulze, Matthias B., Girotto, Giorgia, Böger, Carsten A., Jung, Bettina, 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., 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, Hollander, Anneke Iden, 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., Hunt, Steven C., Walker, Mark, Koistinen, Heikki A., Chandak, Giriraj R., Mercader, Josep M., Costanzo, Maria C., Jang, Dongkeun, Burtt, Noël P., Villalpando, Clicerio Gonzalez, Orozco, Lorena, Fornage, Myriam, Tai, EShyong, 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 N. A., Vitart, Veronique, Hayward, Caroline, Simonsick, Eleanor, van Duijn, Cornelia M., Jin, Zi-Bing, Qu, Jia, Hishigaki, Haretsugu, Lin, Xu, März, Winfried, Gudnason, Vilmundur, Tardif, Jean-Claude, Lettre, Guillaume, Hart, Leen M.‘t, Elders, Petra J. M., Damrauer, Scott M., Kumari, Meena, Kivimaki, Mika, van der Harst, Pim, Spector, Tim D., Loos, Ruth J. F., Province, Michael A., Parra, Esteban J., Cruz, Miguel, Psaty, Bruce M., Brandslund, Ivan, Pramstaller, Peter P., Rotimi, Charles N., Christensen, Kaare, Ripatti, Samuli, Widén, Elisabeth, Hakonarson, Hakon, Grant, Struan F. A., Kiemeney, Lambertus A. L. M., 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, Francesco, Cucca, Mook-Kanamori, Dennis O., van Dijk, Ko Willems, Watkins, Hugh, Strachan, David P., Grarup, Niels, Sever, Peter, Poulter, Neil, Chuang, Lee-Ming, Rotter, Jerome I., Dantoft, Thomas M., Karpe, Fredrik, Neville, Matt J., Timpson, Nicholas J., Cheng, Ching-Yu, Wong, Tien-Yin, Khor, Chiea Chuen, Li, Hengtong, Sabanayagam, Charumathi, Peters, Annette, Gieger, Christian, Hattersley, Andrew T., Pedersen, Nancy L., Magnusson, Patrik K. E., Boomsma, Dorret I., Willemsen, Allegonda H. M., Cupples, LAdrienne, 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., Hazelhurst, Scott, Ramsay, Michèle, 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., Baras, Aris, Justice, Anne E., Buring, Julie E., Ridker, Paul M., Chasman, Daniel I., Kooperberg, Charles, Tamiya, Gen, Yamamoto, Masayuki, van Heel, David A., Trembath, Richard C., 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, Kim, Bong-Jo, Thorsteinsdottir, Unnur, Stefansson, Kari, Zhang, Jifeng, Chen, YEugene, Ho, Yuk-Lam, Lynch, Julie A., Rader, Daniel J., Tsao, Philip S., Chang, Kyong-Mi, Cho, Kelly, O’Donnell, Christopher J., Gaziano, John M., Wilson, Peter W. F., Frayling, Timothy M., Hirschhorn, Joel N., Kathiresan, Sekar, Mohlke, Karen L., Sun, Yan V., Morris, Andrew P., Boehnke, Michael, Brown, Christopher D., Natarajan, Pradeep, Deloukas, Panos, Willer, Cristen J., Assimes, Themistocles L., and Peloso, Gina M.

Published
2022
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33. Genetic Risk Stratification of Primary Open-Angle Glaucoma in Japanese Individuals.

Author

Akiyama, Masato, Tamiya, Gen, Fujiwara, Kohta, Shiga, Yukihiro, Yokoyama, Yu, Hashimoto, Kazuki, Sato, Masataka, Sato, Kota, Narita, Akira, Hashimoto, Sawako, Ueda, Emi, Furuta, Yoshihiko, Hata, Jun, Miyake, Masahiro, Ikeda, Hanako O., Suda, Kenji, Numa, Shogo, Mori, Yuki, Morino, Kazuya, and Murakami, Yusuke

Subjects
*GENETIC risk score, *JAPANESE people, *RECEIVER operating characteristic curves, *OPEN-angle glaucoma, *GENOME-wide association studies
Abstract

To assess the impact of genetic risk estimation for primary open-angle glaucoma (POAG) in Japanese individuals. Cross-sectional analysis. 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). 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. Proportion of patients with POAG after stratification according to the GRS. 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). The GRS showed moderate discriminative accuracy for POAG in the Japanese population. However, risk stratification in the general population showed relatively weak discriminative performance. Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. [ABSTRACT FROM AUTHOR]

Published
2024
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35. Genetic Risk Score for Intracranial Aneurysms: Prediction of Subarachnoid Hemorrhage and Role in Clinical Heterogeneity

Author

Bakker, Mark K., Kanning, Jos P., Abraham, Gad, Martinsen, Amy E., Winsvold, Bendik S., Zwart, John-Anker, Bourcier, Romain, Sawada, Tomonobu, Koido, Masaru, Kamatani, Yoichiro, Morel, Sandrine, Amouyel, Philippe, Debette, Stéphanie, Bijlenga, Philippe, Berrandou, Takiy, Ganesh, Santhi K., Bouatia-Naji, Nabila, Jones, Gregory, Bown, Matthew, Rinkel, Gabriel J.E., Veldink, Jan H., Ruigrok, Ynte M., Hege Aamodt, Anne, Heidi Skogholt, Anne, Brumpton, Ben M, Willer, Cristen J, Sandset, Else C, Kristoffersen, Espen S, Ellekjær, Hanne, Heuch, Ingrid, Nielsen, Jonas B, Hagen, Knut, Hveem, Kristian, Fritsche, Lars G, Thomas, Laurent F, Pedersen, Linda M, Gabrielsen, Maiken E, Holmen, Oddgeir L, Børte, Sigrid, Zhou, Wei, Abboud, Shérine, Pandolfo, Massimo, Thijs, Vincent, Leys, Didier, Bodenant, Marie, Louillet, Fabien, Touzé, Emmanuel, Mas, Jean-Louis, Samson, Yves, Leder, Sara, Léger, Anne, Deltour, Sandrine, Crozier, Sophie, Méresse, Isabelle, Canaple, Sandrine, Godefroy, Olivier, Giroud, Maurice, Béjot, Yannick, Decavel, Pierre, Medeiros, Elizabeth, Montiel, Paola, Moulin, Thierry, Vuillier, Fabrice, Dallongeville, Jean, Metso, Antti J, Metso, Tiina, Tatlisumak, Turgut, Grond-Ginsbach, Caspar, Lichy, Christoph, Kloss, Manja, Werner, Inge, Arnold, Marie-Luise, Dos Santos, Michael, Grau, Armin, Dichgans, Martin, Thomas-Feles, Constanze, Weber, Ralf, Brandt, Tobias, Pezzini, Alessandro, De Giuli, Valeria, Caria, Filomena, Poli, Loris, Padovani, Alessandro, Bersano, Anna, Lanfranconi, Silvia, Beretta, Simone, Ferrarese, Carlo, Giacolone, Giacomo, Paolucci, Stefano, Lyrer, Philippe, Engelter, Stefan, Fluri, Felix, Hatz, Florian, Gisler, Dominique, Bonati, Leo, Gensicke, Henrik, Amort, Margareth, Markus, Hugh, Majersik, Jennifer, Worrall, Bradford, Southerland, Andrew, Cole, John, Kittner, Steven, Evangelou, Evangelos, Warren, Helen R, Gao, He, Ntritsos, Georgios, Dimou, Niki, Esko, Tonu, Mägi, Reedik, Milani, Lili, Almgren, Peter, Boutin, Thibaud, Ding, Jun, Giulianini, Franco, Holliday, Elizabeth G, Jackson, Anne U, Li-Gao, Ruifang, Lin, Wei-Yu, Luan, Jian’an, Mangino, Massimo, Oldmeadow, Christopher, Peter Prins, Bram, Qian, Yong, Sargurupremraj, Muralidharan, Shah, Nabi, Surendran, Praveen, Thériault, Sébastien, Verweij, Niek, Willems, Sara M, Zhao, Jing-Hua, Connell, John, de Mutsert, Renée, Doney, Alex SF, Farrall, Martin, Menni, Cristina, Morris, Andrew D, Noordam, Raymond, Paré, Guillaume, Poulter, Neil R, Shields, Denis C, Stanton, Alice, Thom, Simon, Abecasis, Gonçalo, Amin, Najaf, Arking, Dan E, Ayers, Kristin L, Barbieri, Caterina M, Batini, Chiara, Bis, Joshua C, Blake, Tineka, Bochud, Murielle, Boehnke, Michael, Boerwinkle, Eric, Boomsma, Dorret I, Bottinger, Erwin P, Braund, Peter S, Brumat, Marco, Campbell, Archie, Campbell, Harry, Chakravarti, Aravinda, Chambers, John C, Chauhan, Ganesh, Ciullo, Marina, Cocca, Massimiliano, Collins, Francis, Cordell, Heather J, Davies, Gail, de Borst, Martin H, de Geus, Eco J, Deary, Ian J, Deelen, Joris, Del Greco M, Fabiola, Yusuf Demirkale, Cumhur, Dörr, Marcus, Ehret, Georg B, Elosua, Roberto, Enroth, Stefan, Mesut Erzurumluoglu, A, Ferreira, Teresa, Frånberg, Mattias, Franco, Oscar H, Gandin, Ilaria, Gasparini, Paolo, Giedraitis, Vilmantas, Gieger, Christian, Girotto, Giorgia, Goel, Anuj, Gow, Alan J, Gudnason, Vilmundur, Guo, Xiuqing, Gyllensten, Ulf, Hamsten, Anders, Harris, Tamara B, Harris, Sarah E, Hartman, Catharina A, Havulinna, Aki S, Hicks, Andrew A, Hofer, Edith, Hofman, Albert, Hottenga, Jouke-Jan, Huffman, Jennifer E, Hwang, Shih-Jen, Ingelsson, Erik, James, Alan, Jansen, Rick, Jarvelin, Marjo-Riitta, Joehanes, Roby, Johansson, Åsa, Johnson, Andrew D, Joshi, Peter K, Jousilahti, Pekka, Wouter Jukema, J, Jula, Antti, Kähönen, Mika, Kathiresan, Sekar, Keavney, Bernard D, Khaw, Kay-Tee, Knekt, Paul, Knight, Joanne, Kolcic, Ivana, Kooner, Jaspal S, Koskinen, Seppo, Kristiansson, Kati, Kutalik, Zoltan, Laan, Maris, Larson, Marty, Launer, Lenore J, Lehne, Benjamin, Lehtimäki, Terho, Liewald, David CM, Lin, Li, Lind, Lars, Lindgren, Cecilia M, Liu, YongMei, Loos, Ruth JF, Lopez, Lorna M, Lu, Yingchang, Lyytikäinen, Leo-Pekka, Mahajan, Anubha, Mamasoula, Chrysovalanto, Marrugat, Jaume, Marten, Jonathan, Milaneschi, Yuri, Morgan, Anna, Morris, Andrew P, Morrison, Alanna C, Munson, Peter J, Nalls, Mike A, Nandakumar, Priyanka, Nelson, Christopher P, Niiranen, Teemu, Nolte, Ilja M, Nutile, Teresa, Oldehinkel, Albertine J, Oostra, Ben A, O’Reilly, Paul F, Org, Elin, Padmanabhan, Sandosh, Palmas, Walter, Palotie, Aarno, Pattie, Alison, WJH Penninx, Brenda, Perola, Markus, Peters, Annette, Polasek, Ozren, Pramstaller, Peter P, Tri Nguyen, Quang, Raitakari, Olli T, Rettig, Rainer, Rice, Kenneth, Ridker, Paul M, Ried, Janina S, Riese, Harriëtte, Ripatti, Samuli, Robino, Antonietta, Rose, Lynda M, Rotter, Jerome I, Rudan, Igor, Ruggiero, Daniela, Saba, Yasaman, Sala, Cinzia F, Salomaa, Veikko, Samani, Nilesh J, Sarin, Antti-Pekka, Schmidt, Reinhold, Schmidt, Helena, Shrine, Nick, Siscovick, David, Smith, Albert V, Snieder, Harold, Sõber, Siim, Sorice, Rossella, Starr, John M, Stott, David J, Strachan, David P, Strawbridge, Rona J, Sundström, Johan, Swertz, Morris A, Taylor, Kent D, Teumer, Alexander, Tobin, Martin D, Tomaszewski, Maciej, Toniolo, Daniela, Traglia, Michela, Trompet, Stella, Tuomilehto, Jaakko, Tzourio, Christophe, Uitterlinden, André G, Vaez, Ahmad, van der Most, Peter J, van Duijn, Cornelia M, Verwoert, Germaine C, Vitart, Veronique, Völker, Uwe, Vollenweider, Peter, Vuckovic, Dragana, Watkins, Hugh, Wild, Sarah H, Willemsen, Gonneke, Wilson, James F, Wright, Alan F, Yao, Jie, Zemunik, Tatijana, Zhang, Weihua, Attia, John R, Butterworth, Adam S, Chasman, Daniel I, Conen, David, Cucca, Francesco, Danesh, John, Hayward, Caroline, Howson, Joanna MM, Laakso, Markku, Lakatta, Edward G, Langenberg, Claudia, Melander, Olle, Mook-Kanamori, Dennis O, Palmer, Colin NA, Risch, Lorenz, Scott, Robert A, Scott, Rodney J, Sever, Peter, Spector, Tim D, van der Harst, Pim, Wareham, Nicholas J, Zeggini, Eleftheria, Levy, Daniel, Munroe, Patricia B, Newton-Cheh, Christopher, Brown, Morris J, Metspalu, Andres, Psaty, Bruce M., Wain, Louise V, Elliott, Paul, Caulfield, Mark J, Gormley, Padhraig, Anttila, Verneri, Palta, Priit, Esko, Tonu, Pers, Tune H, Farh, Kai-How, Cuenca-Leon, Ester, Muona, Mikko, Furlotte, Nicholas A, Kurth, Tobias, Ingason, Andres, McMahon, George, Ligthart, Lannie, Terwindt, Gisela M, Kallela, Mikko, Freilinger, Tobias M, Ran, Caroline, Gordon, Scott G, Stam, Anine H, Steinberg, Stacy, Borck, Guntram, Koiranen, Markku, Quaye, Lydia, Adams, Hieab H H, Lehtimäki, Terho, Sarin, Antti-Pekka, Wedenoja, Juho, Hinds, David A, Buring, Julie E, Schürks, Markus, Ridker, Paul M, Gudlaug Hrafnsdottir, Maria, Stefansson, Hreinn, Ring, Susan M, Hottenga, Jouke-Jan, Penninx, Brenda W J H, Färkkilä, Markus, Artto, Ville, Kaunisto, Mari, Vepsäläinen, Salli, Malik, Rainer, Heath, Andrew C, Madden, Pamela A F, Martin, Nicholas G, Montgomery, Grant W, Kurki, Mitja I, Kals, Mart, Mägi, Reedik, Pärn, Kalle, Hämäläinen, Eija, Huang, Hailiang, Byrnes, Andrea E, Franke, Lude, Huang, Jie, Stergiakouli, Evie, Lee, Phil H, Sandor, Cynthia, Webber, Caleb, Cader, Zameel, Muller-Myhsok, Bertram, Schreiber, Stefan, Meitinger, Thomas, Eriksson, Johan G, Salomaa, Veikko, Heikkilä, Kauko, Loehrer, Elizabeth, Uitterlinden, Andre G, Hofman, Albert, van Duijn, Cornelia M, Cherkas, Lynn, Pedersen, Linda M, Stubhaug, Audun, Nielsen, Christopher S, Männikkö, Minna, Mihailov, Evelin, Milani, Lili, Göbel, Hartmut, Esserlind, Ann-Louise, Francke Christensen, Anne, Folkmann Hansen, Thomas, Werge, Thomas, Kaprio, Jaakko, Aromaa, Arpo J, Raitakari, Olli, Arfan Ikram, M, Spector, Tim, Järvelin, Marjo-Riitta, Metspalu, Andres, Kubisch, Christian, Strachan, David P, Ferrari, Michel D, Belin, Andrea C, Dichgans, Martin, Wessman, Maija, van den Maagdenberg, Arn M J M, Boomsma, Dorret I, Davey Smith, George, Stefansson, Kari, Eriksson, Nicholas, Daly, Mark J, Neale, Benjamin M, Olesen, Jes, Chasman, Daniel I, Nyholt, Dale R, Palotie, Aarno, Akiyama, Masato, Alg, Varinder S., Børte, Sigrid, Broderick, Joseph P., Brumpton, Ben M., Dauvillier, Jérôme, Desal, Hubert, Dina, Christian, Friedrich, Christoph M., Gaál-Paavola, Emília I., Gentric, Jean-Christophe, Hirsch, Sven, Hostettler, Isabel C., Houlden, Henry, Hveem, Kristian, Jääskeläinen, Juha E., Johnsen, Marianne Bakke, Li, Liming, Lin, Kuang, Lindgren, Antti, Martin, Olivier, Matsuda, Koichi, Millwood, Iona Y., Naggara, Olivier, Niemelä, Mika, Pera, Joanna, Redon, Richard, Rouleau, Guy A., Sandvei, Marie Søfteland, Schilling, Sabine, Shotar, Eimad, Slowik, Agnieszka, Terao, Chikashi, Verschuren, W. M. Monique, Walters, Robin G., Werring, David J., Willer, Cristen J., Woo, Daniel, Worrall, Bradford B., and Zhou, Sirui

Published
2023
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38. Mendelian randomization analysis does not support causal associations of birth weight with hypertension risk and blood pressure in adulthood

Author

Zheng, Yan, Huang, Tao, Wang, Tiange, Mei, Zhendong, Sun, Zhonghan, Zhang, Tao, Ellervik, Christina, Chai, Jin-Fang, Sim, Xueling, van Dam, Rob M., Tai, E-Shyong, Koh, Woon-Puay, Dorajoo, Rajkumar, Saw, Seang-Mei, Sabanayagam, Charumathi, Wong, Tien Yin, Gupta, Preeti, Rossing, Peter, Ahluwalia, Tarunveer S., Vinding, Rebecca K., Bisgaard, Hans, Bønnelykke, Klaus, Wang, Yujie, Graff, Mariaelisa, Voortman, Trudy, van Rooij, Frank J. A., Hofman, Albert, van Heemst, Diana, Noordam, Raymond, Estampador, Angela C., Varga, Tibor V., Enzenbach, Cornelia, Scholz, Markus, Thiery, Joachim, Burkhardt, Ralph, Orho-Melander, Marju, Schulz, Christina-Alexandra, Ericson, Ulrika, Sonestedt, Emily, Kubo, Michiaki, Akiyama, Masato, Zhou, Ang, Kilpeläinen, Tuomas O., Hansen, Torben, Kleber, Marcus E., Delgado, Graciela, McCarthy, Mark, Lemaitre, Rozenn N., Felix, Janine F., Jaddoe, Vincent W. V., Wu, Ying, Mohlke, Karen L., Lehtimäki, Terho, Wang, Carol A., Pennell, Craig E., Schunkert, Heribert, Kessler, Thorsten, Zeng, Lingyao, Willenborg, Christina, Peters, Annette, Lieb, Wolfgang, Grote, Veit, Rzehak, Peter, Koletzko, Berthold, Erdmann, Jeanette, Munz, Matthias, Wu, Tangchun, He, Meian, Yu, Caizheng, Lecoeur, Cécile, Froguel, Philippe, Corella, Dolores, Moreno, Luis A., Lai, Chao-Qiang, Pitkänen, Niina, Boreham, Colin A., Ridker, Paul M., Rosendaal, Frits R., de Mutsert, Renée, Power, Chris, Paternoster, Lavinia, Sørensen, Thorkild I. A., Tjønneland, Anne, Overvad, Kim, Djousse, Luc, Rivadeneira, Fernando, Lee, Nanette R., Raitakari, Olli T., Kähönen, Mika, Viikari, Jorma, Langhendries, Jean-Paul, Escribano, Joaquin, Verduci, Elvira, Dedoussis, George, König, Inke, Balkau, Beverley, Coltell, Oscar, Dallongeville, Jean, Meirhaeghe, Aline, Amouyel, Philippe, Gottrand, Frédéric, Pahkala, Katja, Niinikoski, Harri, Hyppönen, Elina, März, Winfried, Mackey, David A., Gruszfeld, Dariusz, Tucker, Katherine L., Fumeron, Frédéric, Estruch, Ramon, Ordovas, Jose M., Arnett, Donna K., Mook-Kanamori, Dennis O., Mozaffarian, Dariush, Psaty, Bruce M., North, Kari E., Chasman, Daniel I., and Qi, Lu

Published
2020

40. Regional differences in genes and variants causing retinitis pigmentosa in Japan

Author

Koyanagi, Yoshito, Akiyama, Masato, Nishiguchi, Koji M, Momozawa, Yukihide, Kamatani, Yoichiro, Takata, Sadaaki, Inai, Chihiro, Iwasaki, Yusuke, Kumano, Mikako, Murakami, Yusuke, Komori, Shiori, Gao, Dan, Kurata, Kentaro, Hosono, Katsuhiro, Ueno, Shinji, Hotta, Yoshihiro, Murakami, Akira, Terasaki, Hiroko, Wada, Yuko, Nakazawa, Toru, Ishibashi, Tatsuro, Ikeda, Yasuhiro, Kubo, Michiaki, and Sonoda, Koh-Hei

Published
2021
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42. Deep learning model for extensive smartphone-based diagnosis and triage of cataracts and multiple corneal diseases

Author

Ueno, Yuta, primary, Oda, Masahiro, additional, Yamaguchi, Takefumi, additional, Fukuoka, Hideki, additional, Nejima, Ryohei, additional, Kitaguchi, Yoshiyuki, additional, Miyake, Masahiro, additional, Akiyama, Masato, additional, Miyata, Kazunori, additional, Kashiwagi, Kenji, additional, Maeda, Naoyuki, additional, Shimazaki, Jun, additional, Noma, Hisashi, additional, Mori, Kensaku, additional, and Oshika, Tetsuro, additional

Published
2024
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48. A hypomorphic variant in EYS detected by genome-wide association study contributes toward retinitis pigmentosa

Author

Nishiguchi, Koji M., Miya, Fuyuki, Mori, Yuka, Fujita, Kosuke, Akiyama, Masato, Kamatani, Takashi, Koyanagi, Yoshito, Sato, Kota, Takigawa, Toru, Ueno, Shinji, Tsugita, Misato, Kunikata, Hiroshi, Cisarova, Katarina, Nishino, Jo, Murakami, Akira, Abe, Toshiaki, Momozawa, Yukihide, Terasaki, Hiroko, Wada, Yuko, Sonoda, Koh-Hei, Rivolta, Carlo, Tsunoda, Tatsuhiko, Tsujikawa, Motokazu, Ikeda, Yasuhiro, and Nakazawa, Toru

Published
2021
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50. Trans-biobank analysis with 676,000 individuals elucidates the association of polygenic risk scores of complex traits with human lifespan

Author

Sakaue, Saori, Kanai, Masahiro, Karjalainen, Juha, Akiyama, Masato, Kurki, Mitja, Matoba, Nana, and Takahashi, Atsushi

Subjects
Genetic susceptibility -- Analysis -- Health aspects, Multifactorial traits -- Health aspects -- Analysis, Biological sciences, Health
Abstract

While polygenic risk scores (PRSs) are poised to be translated into clinical practice through prediction of inborn health risks.sup.1, a strategy to utilize genetics to prioritize modifiable risk factors driving heath outcome is warranted.sup.2. To this end, we investigated the association of the genetic susceptibility to complex traits with human lifespan in collaboration with three worldwide biobanks (n.sub.total = 675,898; BioBank Japan (n = 179,066), UK Biobank (n = 361,194) and FinnGen (n = 135,638)). In contrast to observational studies, in which discerning the cause-and-effect can be difficult, PRSs could help to identify the driver biomarkers affecting human lifespan. A high systolic blood pressure PRS was trans-ethnically associated with a shorter lifespan (hazard ratio = 1.03[1.02-1.04], P.sub.meta = 3.9 × 10.sup.-13) and parental lifespan (hazard ratio = 1.06[1.06-1.07], P = 2.0 × 10.sup.-86). The obesity PRS showed distinct effects on lifespan in Japanese and European individuals (P.sub.heterogeneity = 9.5 × 10.sup.-8 for BMI). The causal effect of blood pressure and obesity on lifespan was further supported by Mendelian randomization studies. Beyond genotype-phenotype associations, our trans-biobank study offers a new value of PRSs in prioritization of risk factors that could be potential targets of medical treatment to improve population health. Cross-biobank analysis reveals that polygenic risk scores (PRS) for hypertension and obesity are associated with shorter lifespan, serving as a proof-of-principle that PRS could pinpoint causal risk factors that affect long-term health outcomes., Author(s): Saori Sakaue [sup.1] [sup.2] [sup.3] , Masahiro Kanai [sup.1] [sup.2] [sup.4] [sup.5] [sup.6] [sup.7] [sup.8] , Juha Karjalainen [sup.4] [sup.5] [sup.6] [sup.8] , Masato Akiyama [sup.1] [sup.9] , Mitja [...]

Published
2020
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