Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan
Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, exami...
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2022 |
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In: Ophthalmology Science - Elsevier, 2021, 2(2022), 1, Seite 100113- |
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volume:2 ; year:2022 ; number:1 ; pages:100113- |
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| DOI / URN: |
10.1016/j.xops.2022.100113 |
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DOAJ046896848 |
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| 520 | |a Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. | ||
| 650 | 4 | |a Axial length | |
| 650 | 4 | |a Genome-wide association study | |
| 650 | 4 | |a Population-based cohort study | |
| 653 | 0 | |a Ophthalmology | |
| 700 | 0 | |a Miyuki Sakurai, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Ikuko N. Motoike, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Kaname Kojima, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Takako Takai-Igarashi, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Naoki Nakaya, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Naho Tsuchiya, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Tomohiro Nakamura, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Mami Ishikuro, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Taku Obara, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Akiko Miyazawa, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Kei Homma, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Keisuke Ido, PhD |e verfasserin |4 aut | |
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| 700 | 0 | |a Tomoko Kobayashi, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Ritsuko Shimizu, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Akira Uruno, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Eiichi N. Kodama, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Kichiya Suzuki, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Yohei Hamanaka, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Hiroaki Tomita, MD, PhD |e verfasserin |4 aut | |
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| 700 | 0 | |a Soichi Ogishima, PhD |e verfasserin |4 aut | |
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| 700 | 0 | |a Nobuo Yaegashi, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Shigeo Kure, MD, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Kengo Kinoshita, PhD |e verfasserin |4 aut | |
| 700 | 0 | |a Masayuki Yamamoto, MD, PhD |e verfasserin |4 aut | |
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10.1016/j.xops.2022.100113 doi (DE-627)DOAJ046896848 (DE-599)DOAJ24b1a249dcc44067a7c370d61f462368 DE-627 ger DE-627 rakwb eng RE1-994 Nobuo Fuse, MD, PhD verfasserin aut Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. Axial length Genome-wide association study Population-based cohort study Ophthalmology Miyuki Sakurai, PhD verfasserin aut Ikuko N. Motoike, PhD verfasserin aut Kaname Kojima, PhD verfasserin aut Takako Takai-Igarashi, PhD verfasserin aut Naoki Nakaya, PhD verfasserin aut Naho Tsuchiya, MD, PhD verfasserin aut Tomohiro Nakamura, PhD verfasserin aut Mami Ishikuro, PhD verfasserin aut Taku Obara, PhD verfasserin aut Akiko Miyazawa, MD, PhD verfasserin aut Kei Homma, MD, PhD verfasserin aut Keisuke Ido, PhD verfasserin aut Makiko Taira, MD, PhD verfasserin aut Tomoko Kobayashi, MD, PhD verfasserin aut Ritsuko Shimizu, MD, PhD verfasserin aut Akira Uruno, MD, PhD verfasserin aut Eiichi N. Kodama, MD, PhD verfasserin aut Kichiya Suzuki, MD, PhD verfasserin aut Yohei Hamanaka, MD, PhD verfasserin aut Hiroaki Tomita, MD, PhD verfasserin aut Junichi Sugawara, MD, PhD verfasserin aut Yoichi Suzuki, MD, PhD verfasserin aut Fuji Nagami, PhD verfasserin aut Soichi Ogishima, PhD verfasserin aut Fumiki Katsuoka, PhD verfasserin aut Naoko Minegishi, MD, PhD verfasserin aut Atsushi Hozawa, MD, PhD verfasserin aut Shinichi Kuriyama, MD, PhD verfasserin aut Nobuo Yaegashi, MD, PhD verfasserin aut Shigeo Kure, MD, PhD verfasserin aut Kengo Kinoshita, PhD verfasserin aut Masayuki Yamamoto, MD, PhD verfasserin aut In Ophthalmology Science Elsevier, 2021 2(2022), 1, Seite 100113- (DE-627)1759035246 26669145 nnns volume:2 year:2022 number:1 pages:100113- https://doi.org/10.1016/j.xops.2022.100113 kostenfrei https://doaj.org/article/24b1a249dcc44067a7c370d61f462368 kostenfrei http://www.sciencedirect.com/science/article/pii/S2666914522000021 kostenfrei https://doaj.org/toc/2666-9145 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 2 2022 1 100113- |
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10.1016/j.xops.2022.100113 doi (DE-627)DOAJ046896848 (DE-599)DOAJ24b1a249dcc44067a7c370d61f462368 DE-627 ger DE-627 rakwb eng RE1-994 Nobuo Fuse, MD, PhD verfasserin aut Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. Axial length Genome-wide association study Population-based cohort study Ophthalmology Miyuki Sakurai, PhD verfasserin aut Ikuko N. Motoike, PhD verfasserin aut Kaname Kojima, PhD verfasserin aut Takako Takai-Igarashi, PhD verfasserin aut Naoki Nakaya, PhD verfasserin aut Naho Tsuchiya, MD, PhD verfasserin aut Tomohiro Nakamura, PhD verfasserin aut Mami Ishikuro, PhD verfasserin aut Taku Obara, PhD verfasserin aut Akiko Miyazawa, MD, PhD verfasserin aut Kei Homma, MD, PhD verfasserin aut Keisuke Ido, PhD verfasserin aut Makiko Taira, MD, PhD verfasserin aut Tomoko Kobayashi, MD, PhD verfasserin aut Ritsuko Shimizu, MD, PhD verfasserin aut Akira Uruno, MD, PhD verfasserin aut Eiichi N. Kodama, MD, PhD verfasserin aut Kichiya Suzuki, MD, PhD verfasserin aut Yohei Hamanaka, MD, PhD verfasserin aut Hiroaki Tomita, MD, PhD verfasserin aut Junichi Sugawara, MD, PhD verfasserin aut Yoichi Suzuki, MD, PhD verfasserin aut Fuji Nagami, PhD verfasserin aut Soichi Ogishima, PhD verfasserin aut Fumiki Katsuoka, PhD verfasserin aut Naoko Minegishi, MD, PhD verfasserin aut Atsushi Hozawa, MD, PhD verfasserin aut Shinichi Kuriyama, MD, PhD verfasserin aut Nobuo Yaegashi, MD, PhD verfasserin aut Shigeo Kure, MD, PhD verfasserin aut Kengo Kinoshita, PhD verfasserin aut Masayuki Yamamoto, MD, PhD verfasserin aut In Ophthalmology Science Elsevier, 2021 2(2022), 1, Seite 100113- (DE-627)1759035246 26669145 nnns volume:2 year:2022 number:1 pages:100113- https://doi.org/10.1016/j.xops.2022.100113 kostenfrei https://doaj.org/article/24b1a249dcc44067a7c370d61f462368 kostenfrei http://www.sciencedirect.com/science/article/pii/S2666914522000021 kostenfrei https://doaj.org/toc/2666-9145 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 2 2022 1 100113- |
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10.1016/j.xops.2022.100113 doi (DE-627)DOAJ046896848 (DE-599)DOAJ24b1a249dcc44067a7c370d61f462368 DE-627 ger DE-627 rakwb eng RE1-994 Nobuo Fuse, MD, PhD verfasserin aut Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. Axial length Genome-wide association study Population-based cohort study Ophthalmology Miyuki Sakurai, PhD verfasserin aut Ikuko N. Motoike, PhD verfasserin aut Kaname Kojima, PhD verfasserin aut Takako Takai-Igarashi, PhD verfasserin aut Naoki Nakaya, PhD verfasserin aut Naho Tsuchiya, MD, PhD verfasserin aut Tomohiro Nakamura, PhD verfasserin aut Mami Ishikuro, PhD verfasserin aut Taku Obara, PhD verfasserin aut Akiko Miyazawa, MD, PhD verfasserin aut Kei Homma, MD, PhD verfasserin aut Keisuke Ido, PhD verfasserin aut Makiko Taira, MD, PhD verfasserin aut Tomoko Kobayashi, MD, PhD verfasserin aut Ritsuko Shimizu, MD, PhD verfasserin aut Akira Uruno, MD, PhD verfasserin aut Eiichi N. Kodama, MD, PhD verfasserin aut Kichiya Suzuki, MD, PhD verfasserin aut Yohei Hamanaka, MD, PhD verfasserin aut Hiroaki Tomita, MD, PhD verfasserin aut Junichi Sugawara, MD, PhD verfasserin aut Yoichi Suzuki, MD, PhD verfasserin aut Fuji Nagami, PhD verfasserin aut Soichi Ogishima, PhD verfasserin aut Fumiki Katsuoka, PhD verfasserin aut Naoko Minegishi, MD, PhD verfasserin aut Atsushi Hozawa, MD, PhD verfasserin aut Shinichi Kuriyama, MD, PhD verfasserin aut Nobuo Yaegashi, MD, PhD verfasserin aut Shigeo Kure, MD, PhD verfasserin aut Kengo Kinoshita, PhD verfasserin aut Masayuki Yamamoto, MD, PhD verfasserin aut In Ophthalmology Science Elsevier, 2021 2(2022), 1, Seite 100113- (DE-627)1759035246 26669145 nnns volume:2 year:2022 number:1 pages:100113- https://doi.org/10.1016/j.xops.2022.100113 kostenfrei https://doaj.org/article/24b1a249dcc44067a7c370d61f462368 kostenfrei http://www.sciencedirect.com/science/article/pii/S2666914522000021 kostenfrei https://doaj.org/toc/2666-9145 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 2 2022 1 100113- |
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10.1016/j.xops.2022.100113 doi (DE-627)DOAJ046896848 (DE-599)DOAJ24b1a249dcc44067a7c370d61f462368 DE-627 ger DE-627 rakwb eng RE1-994 Nobuo Fuse, MD, PhD verfasserin aut Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. Axial length Genome-wide association study Population-based cohort study Ophthalmology Miyuki Sakurai, PhD verfasserin aut Ikuko N. Motoike, PhD verfasserin aut Kaname Kojima, PhD verfasserin aut Takako Takai-Igarashi, PhD verfasserin aut Naoki Nakaya, PhD verfasserin aut Naho Tsuchiya, MD, PhD verfasserin aut Tomohiro Nakamura, PhD verfasserin aut Mami Ishikuro, PhD verfasserin aut Taku Obara, PhD verfasserin aut Akiko Miyazawa, MD, PhD verfasserin aut Kei Homma, MD, PhD verfasserin aut Keisuke Ido, PhD verfasserin aut Makiko Taira, MD, PhD verfasserin aut Tomoko Kobayashi, MD, PhD verfasserin aut Ritsuko Shimizu, MD, PhD verfasserin aut Akira Uruno, MD, PhD verfasserin aut Eiichi N. Kodama, MD, PhD verfasserin aut Kichiya Suzuki, MD, PhD verfasserin aut Yohei Hamanaka, MD, PhD verfasserin aut Hiroaki Tomita, MD, PhD verfasserin aut Junichi Sugawara, MD, PhD verfasserin aut Yoichi Suzuki, MD, PhD verfasserin aut Fuji Nagami, PhD verfasserin aut Soichi Ogishima, PhD verfasserin aut Fumiki Katsuoka, PhD verfasserin aut Naoko Minegishi, MD, PhD verfasserin aut Atsushi Hozawa, MD, PhD verfasserin aut Shinichi Kuriyama, MD, PhD verfasserin aut Nobuo Yaegashi, MD, PhD verfasserin aut Shigeo Kure, MD, PhD verfasserin aut Kengo Kinoshita, PhD verfasserin aut Masayuki Yamamoto, MD, PhD verfasserin aut In Ophthalmology Science Elsevier, 2021 2(2022), 1, Seite 100113- (DE-627)1759035246 26669145 nnns volume:2 year:2022 number:1 pages:100113- https://doi.org/10.1016/j.xops.2022.100113 kostenfrei https://doaj.org/article/24b1a249dcc44067a7c370d61f462368 kostenfrei http://www.sciencedirect.com/science/article/pii/S2666914522000021 kostenfrei https://doaj.org/toc/2666-9145 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 2 2022 1 100113- |
| allfieldsSound |
10.1016/j.xops.2022.100113 doi (DE-627)DOAJ046896848 (DE-599)DOAJ24b1a249dcc44067a7c370d61f462368 DE-627 ger DE-627 rakwb eng RE1-994 Nobuo Fuse, MD, PhD verfasserin aut Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan 2022 Text txt rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. Axial length Genome-wide association study Population-based cohort study Ophthalmology Miyuki Sakurai, PhD verfasserin aut Ikuko N. Motoike, PhD verfasserin aut Kaname Kojima, PhD verfasserin aut Takako Takai-Igarashi, PhD verfasserin aut Naoki Nakaya, PhD verfasserin aut Naho Tsuchiya, MD, PhD verfasserin aut Tomohiro Nakamura, PhD verfasserin aut Mami Ishikuro, PhD verfasserin aut Taku Obara, PhD verfasserin aut Akiko Miyazawa, MD, PhD verfasserin aut Kei Homma, MD, PhD verfasserin aut Keisuke Ido, PhD verfasserin aut Makiko Taira, MD, PhD verfasserin aut Tomoko Kobayashi, MD, PhD verfasserin aut Ritsuko Shimizu, MD, PhD verfasserin aut Akira Uruno, MD, PhD verfasserin aut Eiichi N. Kodama, MD, PhD verfasserin aut Kichiya Suzuki, MD, PhD verfasserin aut Yohei Hamanaka, MD, PhD verfasserin aut Hiroaki Tomita, MD, PhD verfasserin aut Junichi Sugawara, MD, PhD verfasserin aut Yoichi Suzuki, MD, PhD verfasserin aut Fuji Nagami, PhD verfasserin aut Soichi Ogishima, PhD verfasserin aut Fumiki Katsuoka, PhD verfasserin aut Naoko Minegishi, MD, PhD verfasserin aut Atsushi Hozawa, MD, PhD verfasserin aut Shinichi Kuriyama, MD, PhD verfasserin aut Nobuo Yaegashi, MD, PhD verfasserin aut Shigeo Kure, MD, PhD verfasserin aut Kengo Kinoshita, PhD verfasserin aut Masayuki Yamamoto, MD, PhD verfasserin aut In Ophthalmology Science Elsevier, 2021 2(2022), 1, Seite 100113- (DE-627)1759035246 26669145 nnns volume:2 year:2022 number:1 pages:100113- https://doi.org/10.1016/j.xops.2022.100113 kostenfrei https://doaj.org/article/24b1a249dcc44067a7c370d61f462368 kostenfrei http://www.sciencedirect.com/science/article/pii/S2666914522000021 kostenfrei https://doaj.org/toc/2666-9145 Journal toc kostenfrei GBV_USEFLAG_A SYSFLAG_A GBV_DOAJ SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_39 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_73 GBV_ILN_74 GBV_ILN_95 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_161 GBV_ILN_170 GBV_ILN_206 GBV_ILN_213 GBV_ILN_224 GBV_ILN_230 GBV_ILN_285 GBV_ILN_293 GBV_ILN_602 GBV_ILN_2001 GBV_ILN_2003 GBV_ILN_2005 GBV_ILN_2006 GBV_ILN_2007 GBV_ILN_2008 GBV_ILN_2009 GBV_ILN_2010 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2026 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2055 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2088 GBV_ILN_2106 GBV_ILN_2110 GBV_ILN_2112 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2232 GBV_ILN_2336 GBV_ILN_2470 GBV_ILN_2507 GBV_ILN_4012 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4249 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4306 GBV_ILN_4307 GBV_ILN_4313 GBV_ILN_4322 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4338 GBV_ILN_4367 GBV_ILN_4393 GBV_ILN_4700 AR 2 2022 1 100113- |
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Nobuo Fuse, MD, PhD @@aut@@ Miyuki Sakurai, PhD @@aut@@ Ikuko N. Motoike, PhD @@aut@@ Kaname Kojima, PhD @@aut@@ Takako Takai-Igarashi, PhD @@aut@@ Naoki Nakaya, PhD @@aut@@ Naho Tsuchiya, MD, PhD @@aut@@ Tomohiro Nakamura, PhD @@aut@@ Mami Ishikuro, PhD @@aut@@ Taku Obara, PhD @@aut@@ Akiko Miyazawa, MD, PhD @@aut@@ Kei Homma, MD, PhD @@aut@@ Keisuke Ido, PhD @@aut@@ Makiko Taira, MD, PhD @@aut@@ Tomoko Kobayashi, MD, PhD @@aut@@ Ritsuko Shimizu, MD, PhD @@aut@@ Akira Uruno, MD, PhD @@aut@@ Eiichi N. Kodama, MD, PhD @@aut@@ Kichiya Suzuki, MD, PhD @@aut@@ Yohei Hamanaka, MD, PhD @@aut@@ Hiroaki Tomita, MD, PhD @@aut@@ Junichi Sugawara, MD, PhD @@aut@@ Yoichi Suzuki, MD, PhD @@aut@@ Fuji Nagami, PhD @@aut@@ Soichi Ogishima, PhD @@aut@@ Fumiki Katsuoka, PhD @@aut@@ Naoko Minegishi, MD, PhD @@aut@@ Atsushi Hozawa, MD, PhD @@aut@@ Shinichi Kuriyama, MD, PhD @@aut@@ Nobuo Yaegashi, MD, PhD @@aut@@ Shigeo Kure, MD, PhD @@aut@@ Kengo Kinoshita, PhD @@aut@@ Masayuki Yamamoto, MD, PhD @@aut@@ |
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<?xml version="1.0" encoding="UTF-8"?><collection xmlns="http://www.loc.gov/MARC21/slim"><record><leader>01000caa a22002652 4500</leader><controlfield tag="001">DOAJ046896848</controlfield><controlfield tag="003">DE-627</controlfield><controlfield tag="005">20230502064127.0</controlfield><controlfield tag="007">cr uuu---uuuuu</controlfield><controlfield tag="008">230227s2022 xx |||||o 00| ||eng c</controlfield><datafield tag="024" ind1="7" ind2=" "><subfield code="a">10.1016/j.xops.2022.100113</subfield><subfield code="2">doi</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-627)DOAJ046896848</subfield></datafield><datafield tag="035" ind1=" " ind2=" "><subfield code="a">(DE-599)DOAJ24b1a249dcc44067a7c370d61f462368</subfield></datafield><datafield tag="040" ind1=" " ind2=" "><subfield code="a">DE-627</subfield><subfield code="b">ger</subfield><subfield code="c">DE-627</subfield><subfield code="e">rakwb</subfield></datafield><datafield tag="041" ind1=" " ind2=" "><subfield code="a">eng</subfield></datafield><datafield tag="050" ind1=" " ind2="0"><subfield code="a">RE1-994</subfield></datafield><datafield tag="100" ind1="0" ind2=" "><subfield code="a">Nobuo Fuse, MD, PhD</subfield><subfield code="e">verfasserin</subfield><subfield code="4">aut</subfield></datafield><datafield tag="245" ind1="1" ind2="0"><subfield code="a">Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan</subfield></datafield><datafield tag="264" ind1=" " ind2="1"><subfield code="c">2022</subfield></datafield><datafield tag="336" ind1=" " ind2=" "><subfield code="a">Text</subfield><subfield code="b">txt</subfield><subfield code="2">rdacontent</subfield></datafield><datafield tag="337" ind1=" " ind2=" "><subfield code="a">Computermedien</subfield><subfield code="b">c</subfield><subfield code="2">rdamedia</subfield></datafield><datafield tag="338" ind1=" " ind2=" "><subfield code="a">Online-Ressource</subfield><subfield code="b">cr</subfield><subfield code="2">rdacarrier</subfield></datafield><datafield tag="520" ind1=" " ind2=" "><subfield code="a">Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. 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Nobuo Fuse, MD, PhD Miyuki Sakurai, PhD Ikuko N. Motoike, PhD Kaname Kojima, PhD Takako Takai-Igarashi, PhD Naoki Nakaya, PhD Naho Tsuchiya, MD, PhD Tomohiro Nakamura, PhD Mami Ishikuro, PhD Taku Obara, PhD Akiko Miyazawa, MD, PhD Kei Homma, MD, PhD Keisuke Ido, PhD Makiko Taira, MD, PhD Tomoko Kobayashi, MD, PhD Ritsuko Shimizu, MD, PhD Akira Uruno, MD, PhD Eiichi N. Kodama, MD, PhD Kichiya Suzuki, MD, PhD Yohei Hamanaka, MD, PhD Hiroaki Tomita, MD, PhD Junichi Sugawara, MD, PhD Yoichi Suzuki, MD, PhD Fuji Nagami, PhD Soichi Ogishima, PhD Fumiki Katsuoka, PhD Naoko Minegishi, MD, PhD Atsushi Hozawa, MD, PhD Shinichi Kuriyama, MD, PhD Nobuo Yaegashi, MD, PhD Shigeo Kure, MD, PhD Kengo Kinoshita, PhD Masayuki Yamamoto, MD, PhD |
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Elektronische Aufsätze |
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Nobuo Fuse, MD, PhD |
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genome-wide association study of axial length in population-based cohorts in japan |
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Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan |
| abstract |
Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. |
| abstractGer |
Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. |
| abstract_unstemmed |
Purpose: To elucidate the differences in ocular biometric parameters by generation and gender and to identify axial length (AL)-associated genetic variants in Japanese individuals, we analyzed Tohoku Medical Megabank Organization (ToMMo) Eye Study data. Design: We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs). Participants: In total, 33 483 participants aged < 18 years who were recruited into the community-based cohort (CommCohort) and the birth and three-generation cohort (BirThree Cohort) of the ToMMo Eye Study were examined. Methods: Each participant was screened with an interview, ophthalmic examinations, and a microarray analysis. The GWASs were performed in 22 379 participants in the CommCohort (discovery stage) and 11 104 participants in the BirThree Cohort (replication stage). We evaluated the associations of single nucleotide polymorphisms (SNPs) with AL using a genome-wide significance threshold (5 × 10-8) in each stage of the study and in the subsequent meta-analysis. Main Outcome Measures: We identified the association of SNPs with AL and distributions of AL in right and left eyes and individuals of different sexes and ages. Results: In the discovery stage, the mean AL of the right eye (23.99 mm) was significantly greater than that of the left eye (23.95 mm). This difference was reproducible across sexes and ages. The GWASs revealed 703 and 215 AL-associated SNPs with genome-wide significance in the discovery and validation stages, respectively, and many of the SNPs in the discovery stage were replicated in the validation stage. Validated SNPs and their associated loci were meta-analyzed for statistical significance (P < 5 × 10-8). This study identified 1478 SNPs spread over 31 loci. Of the 31 loci, 5 are known AL loci, 15 are known refractive-error loci, 4 are known corneal-curvature loci, and 7 loci are newly identified loci that are not known to be associated with AL. Of note, some of them shared functional relationships with previously identified loci. Conclusions: Our large-scale GWASs exploiting ToMMo Eye Study data identified 31 loci linked to variations in AL, 7 of which are newly reported in this article. The results revealed genetic heterogeneity and similarity in SNPs related to ethnic variations in AL. |
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Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan |
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https://doi.org/10.1016/j.xops.2022.100113 https://doaj.org/article/24b1a249dcc44067a7c370d61f462368 http://www.sciencedirect.com/science/article/pii/S2666914522000021 https://doaj.org/toc/2666-9145 |
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Miyuki Sakurai, PhD Ikuko N. Motoike, PhD Kaname Kojima, PhD Takako Takai-Igarashi, PhD Naoki Nakaya, PhD Naho Tsuchiya, MD, PhD Tomohiro Nakamura, PhD Mami Ishikuro, PhD Taku Obara, PhD Akiko Miyazawa, MD, PhD Kei Homma, MD, PhD Keisuke Ido, PhD Makiko Taira, MD, PhD Tomoko Kobayashi, MD, PhD Ritsuko Shimizu, MD, PhD Akira Uruno, MD, PhD Eiichi N. Kodama, MD, PhD Kichiya Suzuki, MD, PhD Yohei Hamanaka, MD, PhD Hiroaki Tomita, MD, PhD Junichi Sugawara, MD, PhD Yoichi Suzuki, MD, PhD Fuji Nagami, PhD Soichi Ogishima, PhD Fumiki Katsuoka, PhD Naoko Minegishi, MD, PhD Atsushi Hozawa, MD, PhD Shinichi Kuriyama, MD, PhD Nobuo Yaegashi, MD, PhD Shigeo Kure, MD, PhD Kengo Kinoshita, PhD Masayuki Yamamoto, MD, PhD |
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Miyuki Sakurai, PhD Ikuko N. Motoike, PhD Kaname Kojima, PhD Takako Takai-Igarashi, PhD Naoki Nakaya, PhD Naho Tsuchiya, MD, PhD Tomohiro Nakamura, PhD Mami Ishikuro, PhD Taku Obara, PhD Akiko Miyazawa, MD, PhD Kei Homma, MD, PhD Keisuke Ido, PhD Makiko Taira, MD, PhD Tomoko Kobayashi, MD, PhD Ritsuko Shimizu, MD, PhD Akira Uruno, MD, PhD Eiichi N. Kodama, MD, PhD Kichiya Suzuki, MD, PhD Yohei Hamanaka, MD, PhD Hiroaki Tomita, MD, PhD Junichi Sugawara, MD, PhD Yoichi Suzuki, MD, PhD Fuji Nagami, PhD Soichi Ogishima, PhD Fumiki Katsuoka, PhD Naoko Minegishi, MD, PhD Atsushi Hozawa, MD, PhD Shinichi Kuriyama, MD, PhD Nobuo Yaegashi, MD, PhD Shigeo Kure, MD, PhD Kengo Kinoshita, PhD Masayuki Yamamoto, MD, PhD |
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| score |
7.4008055 |