Genetic Predisposition to Ischemic Stroke: A Polygenic Risk Score

被引:60
作者
Hachiya, Tsuyoshi [1 ,2 ]
Kamatani, Yoichiro [8 ]
Takahashi, Atsushi [8 ,10 ]
Hata, Jun [11 ,12 ,13 ]
Furukawa, Ryohei [1 ]
Shiwa, Yuh [1 ,2 ]
Yamaji, Taiki [14 ]
Hara, Megumi [15 ]
Tanno, Kozo [3 ]
Ohmomo, Hideki [1 ]
Ono, Kanako [1 ]
Takashima, Naoyuki [16 ]
Matsuda, Koichi [17 ]
Wakai, Kenji [18 ]
Sawada, Norie [14 ]
Iwasaki, Motoki [14 ]
Yamagishi, Kazumasa [20 ]
Ago, Tetsuro [12 ]
Ninomiya, Toshiharu [13 ]
Fukushima, Akimune [4 ]
Hozawa, Atsushi [21 ]
Minegishi, Naoko [22 ]
Satoh, Mamoru [1 ,2 ,5 ]
Endo, Ryujin [6 ]
Sasaki, Makoto [7 ]
Sakata, Kiyomi [3 ]
Kobayashi, Seiichiro [7 ]
Ogasawara, Kuniaki [7 ]
Nakamura, Motoyuki [7 ]
Hitomi, Jiro [7 ]
Kita, Yoshikuni [16 ,24 ]
Tanaka, Keitaro [15 ]
Iso, Hiroyasu [25 ]
Kitazono, Takanari [12 ,13 ]
Kubo, Michiaki [9 ]
Tanaka, Hideo [19 ,26 ]
Tsugane, Shoichiro [14 ]
Kiyohara, Yutaka [27 ]
Yamamoto, Masayuki [23 ]
Sobue, Kenji [7 ]
Shimizu, Atsushi [1 ]
机构
[1] Iwate Med Univ, Div Biomed Informat Anal, Shiwa, Iwate, Japan
[2] Iwate Med Univ, Div Biobank & Data Management, Shiwa, Iwate, Japan
[3] Iwate Med Univ, Div Clin Res & Epidemiol, Shiwa, Iwate, Japan
[4] Iwate Med Univ, Div Innovat & Educ, Shiwa, Iwate, Japan
[5] Iwate Med Univ, Div Community Med Supports & Hlth Record Informat, Shiwa, Iwate, Japan
[6] Iwate Med Univ, Div Publ Relat & Planning, Shiwa, Iwate, Japan
[7] Iwate Med Univ, Iwate Tohoku Med Megabank Org, 2-1-1 Nishitokuta, Shiwa, Iwate 0283694, Japan
[8] RIKEN, Lab Stat Anal, Kanagawa, Japan
[9] RIKEN, Ctr Integrat Med Sci, Kanagawa, Japan
[10] Natl Cerebral & Cardiovasc Ctr, Omics Res Ctr, Lab Omics Informat, Osaka, Japan
[11] Kyushu Univ, Dept Environm Med, Grad Sch Med Sci, Fukuoka, Japan
[12] Kyushu Univ, Dept Med & Clin Sci, Grad Sch Med Sci, Fukuoka, Japan
[13] Kyushu Univ, Ctr Cohort Studies, Grad Sch Med Sci, Fukuoka, Japan
[14] Natl Canc Ctr, Ctr Publ Hlth Sci, Epidemiol & Prevent Grp, Tokyo, Japan
[15] Saga Univ, Fac Med, Dept Prevent Med, Saga, Japan
[16] Shiga Univ Med Sci, Dept Publ Hlth, Shiga, Japan
[17] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Mol Med Lab, Tokyo, Japan
[18] Nagoya Univ, Grad Sch Med, Dept Prevent Med, Nagoya, Aichi, Japan
[19] Nagoya Univ, Grad Sch Med, Dept Epidemiol, Nagoya, Aichi, Japan
[20] Univ Tsukuba, Fac Med, Dept Publ Hlth Med, Tsukuba, Ibaraki, Japan
[21] Tohoku Univ, Tohoku Med Megabank Org, Dept Prevent Med & Epidemiol, Sendai, Miyagi, Japan
[22] Tohoku Univ, Tohoku Med Megabank Org, Dept Biobank, Sendai, Miyagi, Japan
[23] Tohoku Univ, Tohoku Med Megabank Org, Dept Integrat Genom, Sendai, Miyagi, Japan
[24] Tsuruga Nursing Univ, Fac Nursing Sci, Fukui, Japan
[25] Osaka Univ, Dept Social Med, Grad Sch Med, Publ Hlth, Osaka, Japan
[26] Aichi Canc Ctr, Res Inst, Div Epidemiol & Prevent, Nagoya, Aichi, Japan
[27] Hisayama Res Inst Lifestyle Dis, Fukuoka, Japan
基金
日本学术振兴会;
关键词
genome-wide association study; genotype; risk assessment; stroke; GENOME-WIDE ASSOCIATION; JAPANESE POPULATION; CARDIOVASCULAR-DISEASE; SYSTEMATIC ANALYSIS; BLOOD-PRESSURE; HEART-DISEASE; GLOBAL BURDEN; 21; REGIONS; HISAYAMA; SUBTYPES;
D O I
10.1161/STROKEAHA.116.014506
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
Background and Purpose The prediction of genetic predispositions to ischemic stroke (IS) may allow the identification of individuals at elevated risk and thereby prevent IS in clinical practice. Previously developed weighted multilocus genetic risk scores showed limited predictive ability for IS. Here, we investigated the predictive ability of a newer method, polygenic risk score (polyGRS), based on the idea that a few strong signals, as well as several weaker signals, can be collectively informative to determine IS risk. Methods We genotyped 13214 Japanese individuals with IS and 26470 controls (derivation samples) and generated both multilocus genetic risk scores and polyGRS, using the same derivation data set. The predictive abilities of each scoring system were then assessed using 2 independent sets of Japanese samples (KyushuU and JPJM data sets). Results In both validation data sets, polyGRS was shown to be significantly associated with IS, but weighted multilocus genetic risk scores was not. Comparing the highest with the lowest polyGRS quintile, the odds ratios for IS were 1.75 (95% confidence interval, 1.33-2.31) and 1.99 (95% confidence interval, 1.19-3.33) in the KyushuU and JPJM samples, respectively. Using the KyushuU samples, the addition of polyGRS to a nongenetic risk model resulted in a significant improvement of the predictive ability (net reclassification improvement=0.151; P<0.001). Conclusions The polyGRS was shown to be superior to weighted multilocus genetic risk scores as an IS prediction model. Thus, together with the nongenetic risk factors, polyGRS will provide valuable information for individual risk assessment and management of modifiable risk factors.
引用
收藏
页码:253 / 258
页数:6
相关论文
共 33 条
[1]   Genome-wide association study identifies a variant in HDAC9 associated with large vessel ischemic stroke [J].
Bellenguez, Celine ;
Bevan, Steve ;
Gschwendtner, Andreas ;
Spencer, Chris C. A. ;
Burgess, Annette I. ;
Pirinen, Matti ;
Jackson, Caroline A. ;
Traylor, Matthew ;
Strange, Amy ;
Su, Zhan ;
Band, Gavin ;
Syme, Paul D. ;
Malik, Rainer ;
Pera, Joanna ;
Norrving, Bo ;
Lemmens, Robin ;
Freeman, Colin ;
Schanz, Renata ;
James, Tom ;
Poole, Deborah ;
Murphy, Lee ;
Segal, Helen ;
Cortellini, Lynelle ;
Cheng, Yu-Ching ;
Woo, Daniel ;
Nalls, Michael A. ;
Mueller-Myhsok, Bertram ;
Meisinger, Christa ;
Seedorf, Udo ;
Ross-Adams, Helen ;
Boonen, Steven ;
Wloch-Kopec, Dorota ;
Valant, Valerie ;
Slark, Julia ;
Furie, Karen ;
Delavaran, Hossein ;
Langford, Cordelia ;
Deloukas, Panos ;
Edkins, Sarah ;
Hunt, Sarah ;
Gray, Emma ;
Dronov, Serge ;
Peltonen, Leena ;
Gretarsdottir, Solveig ;
Thorleifsson, Gudmar ;
Thorsteinsdottir, Unnur ;
Stefansson, Kari ;
Boncoraglio, Giorgio B. ;
Parati, Eugenio A. ;
Attia, John .
NATURE GENETICS, 2012, 44 (03) :328-U141
[2]   Stroke prevention: an update [J].
Marie-Germaine Bousser .
Frontiers of Medicine, 2012, 6 (1) :22-34
[3]   Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk [J].
Ehret, Georg B. ;
Munroe, Patricia B. ;
Rice, Kenneth M. ;
Bochud, Murielle ;
Johnson, Andrew D. ;
Chasman, Daniel I. ;
Smith, Albert V. ;
Tobin, Martin D. ;
Verwoert, Germaine C. ;
Hwang, Shih-Jen ;
Pihur, Vasyl ;
Vollenweider, Peter ;
O'Reilly, Paul F. ;
Amin, Najaf ;
Bragg-Gresham, Jennifer L. ;
Teumer, Alexander ;
Glazer, Nicole L. ;
Launer, Lenore ;
Zhao, Jing Hua ;
Aulchenko, Yurii ;
Heath, Simon ;
Sober, Siim ;
Parsa, Afshin ;
Luan, Jian'an ;
Arora, Pankaj ;
Dehghan, Abbas ;
Zhang, Feng ;
Lucas, Gavin ;
Hicks, Andrew A. ;
Jackson, Anne U. ;
Peden, John F. ;
Tanaka, Toshiko ;
Wild, Sarah H. ;
Rudan, Igor ;
Igl, Wilmar ;
Milaneschi, Yuri ;
Parker, Alex N. ;
Fava, Cristiano ;
Chambers, John C. ;
Fox, Ervin R. ;
Kumari, Meena ;
Go, Min Jin ;
van der Harst, Pim ;
Kao, Wen Hong Linda ;
Sjogren, Marketa ;
Vinay, D. G. ;
Alexander, Myriam ;
Tabara, Yasuharu ;
Shaw-Hawkins, Sue ;
Whincup, Peter H. .
NATURE, 2011, 478 (7367) :103-109
[4]   Polymorphisms in the lymphotoxin alpha gene and the risk of ischemic stroke in the Japanese population - The Fukuoka Stroke Registry and the Hisayama Study [J].
Hagiwara, Noriko ;
Kitazono, Takanari ;
Kamouchi, Masahiro ;
Kuroda, Junya ;
Ago, Tetsuro ;
Hata, Jun ;
Ninomiya, Toshiharu ;
Ooboshi, Hiroaki ;
Kumai, Yasuhiro ;
Yoshimura, Sohei ;
Tamaki, Kinya ;
Fujii, Kenichiro ;
Nagao, Tetsuhiko ;
Okada, Yasushi ;
Toyoda, Kazunori ;
Nakane, Hiroshi ;
Sugimori, Hiroshi ;
Yamashita, Yoshichika ;
Wakugawa, Yoshiyuki ;
Kubo, Michiaki ;
Tanizaki, Yumihiro ;
Kiyohara, Yutaka ;
Ibayashi, Setsuro ;
Iida, Mitsuo .
CEREBROVASCULAR DISEASES, 2008, 25 (05) :417-422
[5]  
Hamajima N, 2007, ASIAN PAC J CANCER P, V8, P317
[6]   Factors Influencing Participation Rate in a Baseline Survey of a Genetic Cohort in Japan [J].
Hara, Megumi ;
Higaki, Yasuki ;
Imaizumi, Takeshi ;
Taguchi, Naoto ;
Nakamura, Kazuyo ;
Nanri, Hinako ;
Sakamoto, Tatsuhiko ;
Horita, Mikako ;
Shinchi, Koichi ;
Tanaka, Keitaro .
JOURNAL OF EPIDEMIOLOGY, 2010, 20 (01) :40-45
[7]   Genetic Overlap Between Diagnostic Subtypes of Ischemic Stroke [J].
Holliday, Elizabeth G. ;
Traylor, Matthew ;
Malik, Rainer ;
Bevan, Steve ;
Falcone, Guido ;
Hopewell, Jemma C. ;
Cheng, Yu-Ching ;
Cotlarciuc, Ioana ;
Bis, Joshua C. ;
Boerwinkle, Eric ;
Boncoraglio, Giorgio B. ;
Clarke, Robert ;
Cole, John W. ;
Fornage, Myriam ;
Furie, Karen L. ;
Ikram, M. Arfan ;
Jannes, Jim ;
Kittner, Steven J. ;
Lincz, Lisa F. ;
Maguire, Jane M. ;
Meschia, James F. ;
Mosley, Thomas H. ;
Nalls, Mike A. ;
Oldmeadow, Christopher ;
Parati, Eugenio A. ;
Psaty, Bruce M. ;
Rothwell, Peter M. ;
Seshadri, Sudha ;
Scott, Rodney J. ;
Sharma, Pankaj ;
Sudlow, Cathie ;
Wiggins, Kerri L. ;
Worrall, Bradford B. ;
Rosand, Jonathan ;
Mitchell, Braxton D. ;
Dichgans, Martin ;
Markus, Hugh S. ;
Levi, Christopher ;
Attia, John ;
Wray, Naomi R. .
STROKE, 2015, 46 (03) :615-+
[8]   Common variants at 6p21.1 are associated with large artery atherosclerotic stroke [J].
Holliday, Elizabeth G. ;
Maguire, Jane M. ;
Evans, Tiffany-Jane ;
Koblar, Simon A. ;
Jannes, Jim ;
Sturm, Jonathan W. ;
Hankey, Graeme J. ;
Baker, Ross ;
Golledge, Jonathan ;
Parsons, Mark W. ;
Malik, Rainer ;
McEvoy, Mark ;
Biros, Erik ;
Lewis, Martin D. ;
Lincz, Lisa F. ;
Peel, Roseanne ;
Oldmeadow, Christopher ;
Smith, Wayne ;
Moscato, Pablo ;
Barlera, Simona ;
Bevan, Steve ;
Bis, Joshua C. ;
Boerwinkle, Eric ;
Boncoraglio, Giorgio B. ;
Brott, Thomas G. ;
Brown, Robert D., Jr. ;
Cheng, Yu-Ching ;
Cole, John W. ;
Cotlarciuc, Ioana ;
Devan, William J. ;
Fornage, Myriam ;
Furie, Karen L. ;
Gretarsdottir, Solveig ;
Gschwendtner, Andreas ;
Ikram, M. Arfan ;
Longstreth, W. T., Jr. ;
Meschia, James F. ;
Mitchell, Braxton D. ;
Mosley, Thomas H. ;
Nalls, Michael A. ;
Parati, Eugenio A. ;
Psaty, Bruce M. ;
Sharma, Pankaj ;
Stefansson, Kari ;
Thorleifsson, Gudmar ;
Thorsteinsdottir, Unnur ;
Traylor, Matthew ;
Verhaaren, Benjamin F. J. ;
Wiggins, Kerri L. ;
Worrall, Bradford B. .
NATURE GENETICS, 2012, 44 (10) :1147-+
[9]  
Iso H, 2012, J ATHEROSCLER THROMB, V19, P756
[10]   Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation [J].
Kato, Norihiro ;
Loh, Marie ;
Takeuchi, Fumihiko ;
Verweij, Niek ;
Wang, Xu ;
Zhang, Weihua ;
Kelly, Tanika N. ;
Saleheen, Danish ;
Lehne, Benjamin ;
Leach, Irene Mateo ;
Drong, Alexander W. ;
Abbott, James ;
Wahl, Simone ;
Tan, Sian-Tsung ;
Scott, William R. ;
Campanella, Gianluca ;
Chadeau-Hyam, Marc ;
Afzal, Uzma ;
Ahluwalia, Tarunveer S. ;
Bonder, Marc Jan ;
Chen, Peng ;
Dehghan, Abbas ;
Edwards, Todd L. ;
Esko, Tonu ;
Go, Min Jin ;
Harris, Sarah E. ;
Hartiala, Jaana ;
Kasela, Silva ;
Kasturiratne, Anuradhani ;
Khor, Chiea-Chuen ;
Kleber, Marcus E. ;
Li, Huaixing ;
Mok, Zuan Yu ;
Nakatochi, Masahiro ;
Sapari, Nur Sabrina ;
Saxena, Richa ;
Stewart, Alexandre F. R. ;
Stolk, Lisette ;
Tabara, Yasuharu ;
Teh, Ai Ling ;
Wu, Ying ;
Wu, Jer-Yuarn ;
Zhang, Yi ;
Aits, Imke ;
Alves, Alexessander Da Silva Couto ;
Das, Shikta ;
Dorajoo, Rajkumar ;
Hopewell, Jemma C. ;
Kim, Yun Kyoung ;
Koivula, Robert W. .
NATURE GENETICS, 2015, 47 (11) :1282-+