Genome-Wide Polygenic Score and the Risk of Ischemic Stroke in a Prospective Cohort The Hisayama Study

被引：29

作者：

Hachiya, Tsuyoshi ^{[1
]}

Hata, Jun ^{[2
]}

Hirakawa, Yoichiro ^{[3
]}

Yoshida, Daigo ^{[2
]}

Furuta, Yoshihiko ^{[2
]}

Kitazono, Takanari ^{[3
]}

Shimizu, Atsushi ^{[1
]}

Ninomiya, Toshiharu ^{[2
]}

机构：

[1] Iwate Med Univ, Iwate Tohoku Med Megabank Org, Div Biomed Informat Anal, 1-1-1 Idaidori, Shiwa, Iwate 0283694, Japan

[2] Kyushu Univ, Dept Epidemiol & Publ Hlth, Grad Sch Med Sci, Fukuoka, Japan

[3] Kyushu Univ, Dept Med & Clin Sci, Grad Sch Med Sci, Fukuoka, Japan

来源：

STROKE | 2020年 / 51卷 / 03期

关键词：

genotype; humans; Japan; molecular epidemiology; risk factors; COMPLEX TRAITS; CARDIOVASCULAR-DISEASE; HERITABILITY; ASSOCIATION; DESIGN; GENE; PROJECT;

D O I：

10.1161/STROKEAHA.119.027520

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- Environmental and genetic factors contribute to the development of ischemic stroke (IS). We recently developed a genome-wide polygenic risk score (PRS) for IS using case-control datasets from 4 large-scale observational studies conducted in Japan. Our objective in the present study was to confirm the association between the PRS and the risk of IS with data from an independent prospective cohort recruited from the general Japanese population. Methods- A total of 3038 subjects aged >= 40 years were followed up for 10 years (2002-2012). The genome-wide PRS was calculated using genotype data from >350 000 single-nucleotide polymorphisms. The PRS levels were divided into quintiles. High and low genetic risk groups were defined as top 60% and bottom 40% of PRS, respectively. The hazard ratio (HR) for the development of IS was estimated using a Cox proportional hazards model. Results- During the follow-up period, 91 cases developed first-ever IS. The age- and sex-adjusted HR for IS increased with higher PRS levels (P for trend, 0.03). Subjects with the highest quintile level of PRS had a 2.44-fold (95% CI, 1.16-5.12) greater risk for IS than those with the lowest quintile level after adjusting for age and sex. A similar association was observed after adjusting for environmental risk factors (P for trend, 0.03). As compared with low genetic risk group, the age- and sex-adjusted HR in high genetic risk group was 1.63 (95% CI, 1.04-2.55), which was comparable to the HR of hypertension (HR, 1.41), diabetes mellitus (HR, 1.72), and smoking (HR, 1.54). The age- and sex-adjusted HR increased with the number of environmental risk factors in both high and low genetic risk groups without significant interaction. Conclusions- A high genome-wide PRS was a significant risk factor for IS independent of environmental risk factors in a general Japanese population. This finding suggests that PRS may be useful to identify individuals at a high risk of IS.

引用

页码：759 / 765

页数：7

共 39 条

[1]

[Anonymous], 2017, LANCET, DOI DOI 10.1016/S0140-6736(17)32152-9

[2] The Genotype-Tissue Expression (GTEx) pilot analysis: Multitissue gene regulation in humans [J].

Ardlie, Kristin G. ;

DeLuca, David S. ;

Segre, Ayellet V. ;

Sullivan, Timothy J. ;

Young, Taylor R. ;

Gelfand, Ellen T. ;

Trowbridge, Casandra A. ;

Maller, Julian B. ;

Tukiainen, Taru ;

Lek, Monkol ;

Ward, Lucas D. ;

Kheradpour, Pouya ;

Iriarte, Benjamin ;

Meng, Yan ;

Palmer, Cameron D. ;

Esko, Tonu ;

Winckler, Wendy ;

Hirschhorn, Joel N. ;

Kellis, Manolis ;

MacArthur, Daniel G. ;

Getz, Gad ;

Shabalin, Andrey A. ;

Li, Gen ;

Zhou, Yi-Hui ;

Nobel, Andrew B. ;

Rusyn, Ivan ;

Wright, Fred A. ;

Lappalainen, Tuuli ;

Ferreira, Pedro G. ;

Ongen, Halit ;

Rivas, Manuel A. ;

Battle, Alexis ;

Mostafavi, Sara ;

Monlong, Jean ;

Sammeth, Michael ;

Mele, Marta ;

Reverter, Ferran ;

Goldmann, Jakob M. ;

Koller, Daphne ;

Guigo, Roderic ;

McCarthy, Mark I. ;

Dermitzakis, Emmanouil T. ;

Gamazon, Eric R. ;

Im, Hae Kyung ;

Konkashbaev, Anuar ;

Nicolae, Dan L. ;

Cox, Nancy J. ;

Flutre, Timothee ;

Wen, Xiaoquan ;

Stephens, Matthew .

SCIENCE, 2015, 348 (6235) :648-660

[3] Genetic liability in stroke - A long-term follow-up study of Danish twins [J].

Bak, S ;

Gaist, D ;

Sindrup, SH ;

Skytthe, A ;

Christensen, K .

STROKE, 2002, 33 (03) :769-774

[4] Genetic Heritability of Ischemic Stroke and the Contribution of Previously Reported Candidate Gene and Genomewide Associations [J].

Bevan, Steve ;

Traylor, Matthew ;

Adih-Samii, Poneh ;

Malik, Rainer ;

Paul, Nicola L. M. ;

Jackson, Caroline ;

Farrall, Martin ;

Rothwell, Peter M. ;

Sudlow, Cathie ;

Dichgans, Martin ;

Markus, Hugh S. .

STROKE, 2012, 43 (12) :3161-+

[5] An Expanded View of Complex Traits: From Polygenic to Omnigenic [J].

Boyle, Evan A. ;

Li, Yang I. ;

Pritchard, Jonathan K. .

CELL, 2017, 169 (07) :1177-1186

[6] Partitioning heritability by functional annotation using genome-wide association summary statistics [J].

Finucane, Hilary K. ;

Bulik-Sullivan, Brendan ;

Gusev, Alexander ;

Trynka, Gosia ;

Reshef, Yakir ;

Loh, Po-Ru ;

Anttila, Verneri ;

Xu, Han ;

Zang, Chongzhi ;

Farh, Kyle ;

Ripke, Stephan ;

Day, Felix R. ;

Purcell, Shaun ;

Stahl, Eli ;

Lindstrom, Sara ;

Perry, John R. B. ;

Okada, Yukinori ;

Raychaudhuri, Soumya ;

Daly, Mark J. ;

Patterson, Nick ;

Neale, Benjamin M. ;

Price, Alkes L. .

NATURE GENETICS, 2015, 47 (11) :1228-+

[7]

Fisher R. A., 1919, Transactions of the Royal Society of Edinburgh, V52

[8] Genome-wide analysis of polymorphism x sodium interaction effect on blood pressure identifies a novel 3′-BCL11B gene desert locus [J].

Hachiya, Tsuyoshi ;

Narita, Akira ;

Ohmomo, Hideki ;

Sutoh, Yoichi ;

Komaki, Shohei ;

Tanno, Kozo ;

Satoh, Mamoru ;

Sakata, Kiyomi ;

Hitomi, Jiro ;

Nakamura, Motoyuki ;

Ogasawara, Kuniaki ;

Yamamoto, Masayuki ;

Sasaki, Makoto ;

Hozawa, Atsushi ;

Shimizu, Atsushi .

SCIENTIFIC REPORTS, 2018, 8

[9] Genome-wide meta-analysis in Japanese populations identifies novel variants at the TMC6-TMC8 and SIX3-SIX2 loci associated with HbA1c [J].

Hachiya, Tsuyoshi ;

Komaki, Shohei ;

Hasegawa, Yutaka ;

Ohmomo, Hideki ;

Tanno, Kozo ;

Hozawa, Atsushi ;

Tamiya, Gen ;

Yamamoto, Masayuki ;

Ogasawara, Kuniaki ;

Nakamura, Motoyuki ;

Hitomi, Jiro ;

Ishigaki, Yasushi ;

Sasaki, Makoto ;

Shimizu, Atsushi .

SCIENTIFIC REPORTS, 2017, 7

[10] Genome-wide identification of inter-individually variable DNA methylation sites improves the efficacy of epigenetic association studies [J].

Hachiya, Tsuyoshi ;

Furukawa, Ryohei ;

Shiwa, Yuh ;

Ohmomo, Hideki ;

Ono, Kanako ;

Katsuoka, Fumiki ;

Nagasaki, Masao ;

Yasuda, Jun ;

Fuse, Nobuo ;

Kinoshita, Kengo ;

Yamamoto, Masayuki ;

Tanno, Kozo ;

Satoh, Mamoru ;

Endo, Ryujin ;

Sasaki, Makoto ;

Sakata, Kiyomi ;

Kobayashi, Seiichiro ;

Ogasawara, Kuniaki ;

Hitomi, Jiro ;

Sobue, Kenji ;

Shimizu, Atsushi .

NPJ GENOMIC MEDICINE, 2017, 2

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