Dataset Information

Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.

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.

SUBMITTER: Fuse N

PROVIDER: S-EPMC9559092 | biostudies-literature | 2022 Mar

REPOSITORIES: biostudies-literature

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Publications

Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.

Fuse Nobuo N Sakurai Miyuki M Motoike Ikuko N IN Kojima Kaname K Takai-Igarashi Takako T Nakaya Naoki N Tsuchiya Naho N Nakamura Tomohiro T Ishikuro Mami M Obara Taku T Miyazawa Akiko A Homma Kei K Ido Keisuke K Taira Makiko M Kobayashi Tomoko T Shimizu Ritsuko R Uruno Akira A Kodama Eiichi N EN Suzuki Kichiya K Hamanaka Yohei Y Tomita Hiroaki H Sugawara Junichi J Suzuki Yoichi Y Nagami Fuji F Ogishima Soichi S Katsuoka Fumiki F Minegishi Naoko N Hozawa Atsushi A Kuriyama Shinichi S Yaegashi Nobuo N Kure Shigeo S Kinoshita Kengo K Yamamoto Masayuki M

Ophthalmology science 20220122 1

<h4>Purpose</h4>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.<h4>Design</h4>We designed the ToMMo Eye Study, examined AL variations, and conducted genome-wide association studies (GWASs).<h4>Participants</h4>In total, 33 483 participants aged > 18 years who were recruited into the community-based coh ...[more]

PMID: 36246171

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Project description:The Great East Japan Earthquake (GEJE) and resulting tsunami of March 11, 2011 gave rise to devastating damage on the Pacific coast of the Tohoku region. The Tohoku Medical Megabank Project (TMM), which is being conducted by Tohoku University Tohoku Medical Megabank Organization (ToMMo) and Iwate Medical University Iwate Tohoku Medical Megabank Organization (IMM), has been launched to realize creative reconstruction and to solve medical problems in the aftermath of this disaster. We started two prospective cohort studies in Miyagi and Iwate Prefectures: a population-based adult cohort study, the TMM Community-Based Cohort Study (TMM CommCohort Study), which will recruit 80 000 participants, and a birth and three-generation cohort study, the TMM Birth and Three-Generation Cohort Study (TMM BirThree Cohort Study), which will recruit 70 000 participants, including fetuses and their parents, siblings, grandparents, and extended family members. The TMM CommCohort Study will recruit participants from 2013 to 2016 and follow them for at least 5 years. The TMM BirThree Cohort Study will recruit participants from 2013 to 2017 and follow them for at least 4 years. For children, the ToMMo Child Health Study, which adopted a cross-sectional design, was also started in November 2012 in Miyagi Prefecture. An integrated biobank will be constructed based on the two prospective cohort studies, and ToMMo and IMM will investigate the chronic medical impacts of the GEJE. The integrated biobank of TMM consists of health and clinical information, biospecimens, and genome and omics data. The biobank aims to establish a firm basis for personalized healthcare and medicine, mainly for diseases aggravated by the GEJE in the two prefectures. Biospecimens and related information in the biobank will be distributed to the research community. TMM itself will also undertake genomic and omics research. The aims of the genomic studies are: 1) to construct an integrated biobank; 2) to return genomic research results to the participants of the cohort studies, which will lead to the implementation of personalized healthcare and medicine in the affected areas in the near future; and 3) to contribute the development of personalized healthcare and medicine worldwide. Through the activities of TMM, we will clarify how to approach prolonged healthcare problems in areas damaged by large-scale disasters and how useful genomic information is for disease prevention.

Project description:BackgroundGenome cohort studies are used to analyze interactions between genetic and environmental factors, providing valuable information for personalized healthcare. Large-scale and long-term cohort studies require a number of specially trained personnel, of whom those involved in obtaining informed consent play a vital role, especially during the initial phase of such studies. The Japanese Society of Human Genetics (JSHG) previously established a certification system for genome medical research coordinators (GMRCs) responsible for obtaining written consent via face-to-face explanation. Meanwhile, in the Tohoku Medical Megabank Organization (ToMMo), GMRCs are expected to play important roles not only in obtaining informed consent and conducting various assessments, but also in communicating with participants throughout the long-term follow-up. Based on the JSHG program, we therefore developed a specific education and training program for ToMMo GMRCs consisting of 17 lectures, one practical training session on the informed consent procedure, and written and interview examinations. Re-education workshops aimed at self-improvement are also carried out following certification. In this study, we evaluated the education and training program in terms of overall understanding, usefulness, and satisfaction using an anonymous questionnaire.MethodsAn anonymous questionnaire addressing each aspect of the education and training program (understanding, usefulness, and satisfaction) was distributed among 152 qualified ToMMo GMRCs. Responses were received from 94 participants (61.8%).ResultsThere was a significant association between the level of overall understanding of lectures and medical qualification (nurse or clinical laboratory technologist), but not with age or educational background. The level of understanding and overall usefulness were lower in sessions related to genetics and epidemiology than those dealing with ToMMo practices. In the re-education workshops, GMRCs showed a preference for and hoped to learn more about both background knowledge and research progress in the ToMMo.ConclusionsThe results of our questionnaire suggest that not all ToMMo GMRCs are able to understand everything during the initial education and training program, especially in terms of genomic medicine. Continuous re-education is therefore vital in improving knowledge, skills and motivation, and preparing GMRCs for a specialist role in community-based personalized healthcare.

Project description:BackgroundUpper and lower extremity muscle strength can be used to predict health outcomes. However, the difference between the relation of upper extremity muscle and of lower extremity muscle with physiological factors is unclear. This study aimed to evaluate the association between physiological data and muscle strength, measured using grip and leg extension strength, among Japanese adults.MethodsWe conducted a cross-sectional study of 2,861 men and 6,717 women aged ≥ 20 years living in Miyagi Prefecture, Japan. Grip strength was measured using a dynamometer. Leg extension strength was measured using a hydraulic isokinetic leg press machine. Anthropometry and physiological data, including blood pressure, calcaneal ultrasound bone status, pulmonary function, carotid echography, and blood information, were assessed. We used a general linear model adjusted for age, body composition, and smoking status to evaluate the association between muscle strength and physiological factors.ResultsGrip and leg extension strength were positively associated with bone area ratio, vital capacity, forced vital capacity, forced expiratory volume in one second, and estimated glomerular filtration rate, and negatively associated with waist circumference and percentage body fat mass in both the sexes. Diastolic blood pressure was positively associated with grip strength in both the sexes and leg extension strength in men, but not women. High-density lipoprotein cholesterol and red blood cell counts were positively associated with grip and leg extension strength in women, but not men. In both the sexes, pulse rate, total cholesterol, and uric acid were consistently associated with only leg extension strength, but not grip strength. In women, glycated hemoglobin demonstrated negative and positive associations with grip and leg extension strength, respectively.ConclusionsGrip and leg extension strength demonstrated similar associations with anthropometry, pulmonary function, and estimated glomerular filtration rate, but the associations with the other factors were not always consistent.

Project description:A baseline oral microbiome study of the Tohoku Medical Megabank Organization (TMM) was planned to characterize the profile of the oral microbiome in the Japanese population. The study also aimed to clarify risk factors for multifactorial diseases by integrated analysis of the oral microbiome and host genome/omics information. From 2013 to 2016, we collected three types of oral biospecimens, saliva, supragingival plaque, and tongue swab, from a total of 25,101 participants who had a dental examination in TMM. In this study, we used two independent cohorts; the Community-Based Cohort and Birth and Three-Generation Cohort as discovery and validation cohorts, respectively, and we selected participants examined by a single dentist. We found through the 16S ribosomal RNA gene sequencing analysis of 834 participants of the Community-Based Cohort Study that there are differences in the microbial composition and community structure between saliva and plaque. The species diversities in both saliva and plaque were increased in correlation with the severity of periodontal disease. These results were nicely reproduced in the analysis of 455 participants of the Birth and Three-Generation Cohort Study. In addition, strong positive and negative associations of microbial taxa in both plaque and saliva with periodontitis-associated biofilm formation were detected by co-occurrence network analysis. The classes Actinobacteria and Bacilli, including oral health-associated bacterial species, showed a positive correlation in saliva. These results revealed differences in microbial composition and community structure between saliva and plaque and a correlation between microbial species and the severity of periodontal disease. We expect that the large database of the oral microbiome in the TMM biobank will help in the discovery of novel targets for the treatment and prevention of oral diseases, as well as for the discovery of therapeutic and/or preventive targets of systemic diseases.

Project description:PURPOSE:To assess the normal distribution of axial length and its associations in a population of Russia. METHODS:The population-based Ural Eye and Medical Study included 5,899 (80.5%) individuals out of 7328 eligible individuals aged 40+ years. The participants underwent an ocular and systemic examination. Axial length was measured sonographically (Ultra-compact A/B/P ultrasound system, Quantel Medical, Cournon d'Auvergne, France). RESULTS:Biometric data were available for 5707 (96.7%) individuals with a mean age of 58.8±10.6 years (range:40-94 years; 25%, 50%, 75% quartile: 51.0, 58.0, 66.0 years, respectively). Mean axial length was 23.30±1.10 mm (range: 19.02-32.87mm; 95% confidence interval (CI): 21.36-25.89; 25%, 50%, 75% quartile: 22.65mm, 23.23mm, 23.88mm, resp.). Prevalences of moderate myopia (axial length:24.5-<26.5mm) and high myopia (axial length >26.5mm) were 555/5707 (8.7%;95%CI:9.0,10.5) and 78/5707 (1.4%;95%CI:1.1,1.7), respectively. Longer axial length (mean:23.30±1.10mm) was associated (correlation coefficient r2:0.70) with older age (P<0.001;standardized regression coefficient beta:0.14), taller body height (P<0.001;beta:0.07), higher level of education (P<0.001;beta:0.04), higher intraocular pressure (P<0.001;beta:0.03), more myopic spherical refractive error (P<0.001;beta:-0.55), lower corneal refractive power (P<0.001;beta:-0.44), deeper anterior chamber depth (P<0.001;beta:0.20), wider anterior chamber angle (P<0.001;beta:0.05), thinner peripapillary retinal nerve fiber layer thickness (P<0.001;beta:-0.04), higher degree of macular fundus tessellation (P<0.001;beta:0.08), lower prevalence of epiretinal membranes (P = 0.01;beta-0.02) and pseudoexfoliation (P = 0.007;beta:-0.02) and higher prevalence of myopic maculopathy (P<0.001;beta:0.08). In that model, prevalence of age-related macular degeneration (any type: P = 0.84; early type: P = 0.46), diabetic retinopathy (P = 0.16), and region of habitation (P = 0.27) were not significantly associated with axial length. CONCLUSIONS:Mean axial length in this typically multi-ethnic Russian study population was comparable with values from populations in Singapore and Beijing. In contrast to previous studies, axial length was not significantly related with the prevalences of age-related macular degeneration and diabetic retinopathy or region of habitation.

Project description:BackgroundThere is inconsistent evidence on the associations of education and work status with alcohol use during pregnancy. Our aim was to examine the associations of education and work status with alcohol use and alcohol cessation during pregnancy in Japan.MethodsData were analyzed from 11,839 pregnant women who participated in the Tohoku Medical Megabank Project Birth and Three-Generation Cohort Study from 2013 to 2017 in Japan. Women were dichotomized as current drinkers or non-drinkers in both early and middle pregnancy. Alcohol cessation was defined as alcohol use in early pregnancy, but not in middle pregnancy. Multivariable log-binomial regression analyses were conducted to examine associations of education and work status with alcohol use in early and middle pregnancy and alcohol cessation, adjusted for age and income. The prevalence ratios (PRs) and 95% confidence intervals (CIs) were calculated by work status and education.ResultsThe prevalence of alcohol use in early and middle pregnancy was 20.9 and 6.4%, respectively. Higher education was associated with alcohol use in early pregnancy both among working and non-working women; the PRs of university education or higher compared with high school education or lower were 1.62 (95% CI, 1.34-1.96) and 1.29 (95% CI, 1.16-1.45), respectively. Higher education was associated with alcohol cessation during pregnancy among working women; the corresponding PR was 1.09 (95% CI, 1.01-1.17). Working was associated with alcohol use in early and middle pregnancy. Working was associated with a decreased probability of alcohol cessation among women with lower education but with an increased probability of alcohol cessation among women with higher education; the PRs of working compared with not working were 0.91 (95% CI, 0.82-1.00) and 1.10 (95% CI, 1.00-1.20), respectively.ConclusionsWomen with higher education were more likely to consume alcohol in early pregnancy and to cease alcohol use between early and middle pregnancy, especially working women. Working women were more likely to consume alcohol throughout pregnancy. Working women with lower education were less likely to cease alcohol use, whereas working women with higher education were more likely to cease alcohol use between early and middle pregnancy.

Dataset Information

Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.

Purpose

Design

Participants

Methods

Main outcome measures

Results

Conclusions

Publications

Genome-wide Association Study of Axial Length in Population-based Cohorts in Japan: The Tohoku Medical Megabank Organization Eye Study.

Similar Datasets

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