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Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium

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机构: [1]NHGRI, NIH, Baltimore, MD 21224 USA [2]Johns Hopkins Bloomberg Sch Publ Hlth, Dept Epidemiol, Baltimore, MD USA [3]Johns Hopkins Med Inst, Wilmer Eye Inst, Baltimore, MD 21205 USA [4]Kings Coll London, Dept Twin Res & Genet Epidemiol, London, England [5]Erasmus MC, Dept Ophthalmol, Rotterdam, Netherlands [6]Erasmus MC, Dept Epidemiol, Rotterdam, Netherlands [7]Singapore Eye Res Inst, Singapore, Singapore [8]Natl Univ Singapore, Yong Loo Lin Sch Med, Dept Ophthalmol, Singapore 117595, Singapore [9]Duke NUS Grad Med Sch, Off Clin Sci, Singapore, Singapore [10]Univ Med Ctr Mainz, Dept Ophthalmol, Mainz, Germany [11]Klin Pallas, Olten, Switzerland [12]Univ Edinburgh, Inst Genet & Mol Med, Med Res Council Human Genet Unit, Edinburgh EH4 2XU, Midlothian, Scotland [13]Univ Melbourne, Royal Victorian Eye & Ear Hosp, Ctr Eye Res Australia, Melbourne, Vic, Australia [14]Univ Western Australia, Lions Eye Inst, Ctr Ophthalmol & Visual Sci, Perth, WA 6009, Australia [15]Tech Univ Munich, Klinikum Rechts Isar, Inst Human Genet, D-80290 Munich, Germany [16]Tampere Univ Hosp, Dept Clin Chem, Tampere 33520, Finland [17]Univ Tampere, Sch Med, Tampere 33520, Finland [18]Royal Brisbane Hosp, QIMR Berghofer Med Res Inst, Brisbane, Qld 4029, Australia [19]CNR, Inst Populat Genet, I-07040 Sassari, Italy [20]Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 117548, Singapore [21]Univ Bristol, MRC Integrat Epidemiol Unit IEU, Bristol BS8 2BN, Avon, England [22]Univ Bristol, Sch Social & Community Med, Bristol BS8 2BN, Avon, England [23]UCL Inst Child Hlth, Ctr Epidemiol & Biostat, London, England [24]UCL, Inst Ophthalmol, London, England [25]UCL Inst Child Hlth, Ulverscroft Vis Res Grp, London, England [26]Capital Univ Med Sci, Beijing Tongren Hosp, Beijing Inst Ophthalmol, Beijing, Peoples R China [27]Univ Split, Fac Med, Split, Croatia [28]Univ Edinburgh, Ctr Populat Hlth Sci, Edinburgh EH8 9AG, Midlothian, Scotland [29]Sisters Mercy Univ Hosp, Dept Ophthalmol, Zagreb, Croatia [30]Univ Helsinki, Hjelt Inst, Dept Publ Hlth, Helsinki, Finland [31]Univ Helsinki, Cent Hosp, Dept Ophthalmol, Helsinki, Finland [32]Univ Heart Ctr Hamburg, Clin Gen & Intervent Cardiol, Hamburg, Germany [33]Med Univ Lubeck, Univ Hosp Schleswig Holstein, Inst Med Biometry & Stat, D-23538 Lubeck, Germany [34]DZHK German Ctr Cardiovasc Res, Lubeck, Germany [35]Dardenne Eye Hosp, Bonn, Germany [36]Univ Med Ctr Mainz, Inst Clin Chem & Lab Med, Mainz, Germany [37]Hong Kong Polytech Univ, Dept Hlth Technol & Informat, Hong Kong, Hong Kong, Peoples R China [38]Hong Kong Polytech Univ, Sch Optometry, Ctr Myopia Res, Kowloon, Hong Kong, Peoples R China [39]Helmholtz Zentrum Munchen, Inst Genet Epidemiol, Neuherberg, Germany [40]Princess Alexandra Eye Pavil, Edinburgh EH3 9HA, Midlothian, Scotland [41]Netherlands Genom Initiat, Netherlands Consortium Hlth Ageing, The Hague, Netherlands [42]Erasmus MC, Dept Internal Med, Rotterdam, Netherlands [43]Erasmus MC, Dept Clin Genet, Rotterdam, Netherlands [44]Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 117548, Singapore [45]Natl Univ Singapore, Dept Med, Singapore 117548, Singapore [46]Natl Univ Hlth Syst, Singapore, Singapore [47]Duke Natl Univ Singapore Grad Med Sch, Singapore, Singapore [48]Duke NUS Grad Med Sch, NBD Program, Singapore, Singapore [49]Hosp Sick Children Res Inst, Genet & Genome Biol Program, Toronto, ON M5G 0A4, Canada [50]Tampere Univ Hosp, Dept Clin Physiol, Tampere 33521, Finland [51]Univ Tampere, Sch Med, Tampere 33521, Finland [52]Univ Turku, Res Ctr Appl & Prevent Cardiovasc Med, Turku, Finland [53]Turku Univ Hosp, Dept Clin Physiol & Nucl Med, Turku 20041, Finland [54]Univ Queensland, Diamantina Inst, Translat Res Inst, Brisbane, Qld, Australia [55]Genome Inst Singapore, Div Human Genet, Singapore, Singapore [56]Duke Univ, Sch Med, Duke Eye Ctr, Durham, NC USA [57]Univ Sydney, Sydney, NSW 2006, Australia [58]Western Sydney Local Hlth Network, Sydney, NSW, Australia [59]Westmead Millennium Inst, Westmead, NSW, Australia [60]Univ Wisconsin Madison, Madison, WI 53726 USA [61]Capital Med Univ, Beijing Ophthalmol & Visual Sci Key Lab, Beijing Tongren Hosp, Beijing Inst Ophthalmol,Beijing Tongren Eye Ctr, Beijing, Peoples R China [62]Heidelberg Univ, Med Fac Mannheim, Dept Ophthalmol, Mannheim, Germany [63]Univ Jyvaskyla, Dept Hlth Sci, Jyvaskyla, Finland [64]Univ Jyvaskyla, Gerontol Res Ctr, Jyvaskyla, Finland [65]Cent Hosp Cent Finland, Dept Ophthalmol, Jyvaskyla, Finland [66]Univ Penn, Sch Med, Philadelphia, PA 19104 USA [67]Kings Coll London, Dept Ophthalmol, London, England [68]Univ Toronto, Dala Lanna Sch Publ Hlth, Toronto, ON, Canada
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To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged < 25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged < 25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise. Genome-wide association analysis was carried out for each cohort separately using logistic regression. Meta-analysis was conducted using a fixed effects model. In the older European group the most strongly associated marker was downstream of the neurexin-1 (NRXN1) gene (rs1401327, P = 3.92E-8). No other region reached genome-wide significance, and association signals were lower for the younger European group and Asian group. In the meta-analysis of all cohorts, no marker reached genome-wide significance: The most strongly associated regions were, NRXN1 (rs1401327, P = 2.93E-07), TOX (rs7823467, P = 3.47E-07) and LINC00340 (rs12212674, P = 1.49E-06). For 34 markers identified in prior GWAS for spherical equivalent refractive error, the beta coefficients for genotype versus spherical equivalent, and genotype versus refractive astigmatism, were highly correlated (r = -0.59, P = 2.10E-04). This work revealed no consistent or strong genetic signals for refractive astigmatism; however, the TOX gene region previously identified in GWAS for spherical equivalent refractive error was the second most strongly associated region. Analysis of additional markers provided evidence supporting widespread genetic co-susceptibility for spherical and astigmatic refractive errors.

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出版当年[2014]版:
大类 | 2 区 生物
小类 | 2 区 遗传学
最新[2025]版:
大类 | 2 区 生物学
小类 | 2 区 遗传学
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出版当年[2013]版:
Q1 GENETICS & HEREDITY
最新[2023]版:
Q2 GENETICS & HEREDITY

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第一作者机构: [1]NHGRI, NIH, Baltimore, MD 21224 USA
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