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1.
Life (Basel) ; 11(3)2021 Mar 22.
Artigo em Inglês | MEDLINE | ID: mdl-33809962

RESUMO

Concentric retinitis pigmentosa (RP), in which retinal degeneration is limited in the periphery, is rare and little information exists to date on the subject. Herein, we describe the clinical and genetic characteristics of this atypical form of RP. We retrospectively reviewed our database and identified 14 patients with concentric RP. Additionally, 14 patients with age-matched typical RP were also included. Patients with concentric RP had better visual acuity (logarithm of minimum angle of resolution -0.04 vs. 0.32, p = 0.047) and preserved ellipsoid zones (7630 µm vs. 2646 µm, p < 0.001) compared to typical RP. The electroretinogram showed subnormal but recordable responses in patients with concentric RP. Genetic testing was done in nine patients with concentric RP and revealed causative mutations in the EYS gene in one patient and the RP9 gene in one patient. Two patients had myotonic dystrophy and the diagnosis was revised as myotonic dystrophy-associated retinopathy. Concentric RP is a rare, atypical form of RP with better visual function. There is some overlap in the causative genes in concentric and typical RP. Myotonic dystrophy-associated retinopathy is an important differential diagnosis.

2.
Proc Natl Acad Sci U S A ; 118(11)2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33649182

RESUMO

HTLV-1-associated myelopathy (HAM/TSP) is a chronic and progressive inflammatory disease of the central nervous system. The aim of our study was to identify genetic determinants related to the onset of HAM/TSP in the Japanese population. We conducted a genome-wide association study comprising 753 HAM/TSP patients and 899 asymptomatic HTLV-1 carriers. We also performed comprehensive genotyping of HLA-A, -B, -C, -DPB1, -DQB1, and -DRB1 genes using next-generation sequencing technology for 651 HAM/TSP patients and 804 carriers. A strong association was observed in HLA class I (P = 1.54 × 10-9) and class II (P = 1.21 × 10-8) loci with HAM/TSP. Association analysis using HLA genotyping results showed that HLA-C*07:02 (P = 2.61 × 10-5), HLA-B*07:02 (P = 4.97 × 10-10), HLA-DRB1*01:01 (P = 1.15 × 10-9) and HLA-DQB1*05:01 (P = 2.30 × 10-9) were associated with disease risk, while HLA-B*40:06 (P = 3.03 × 10-5), HLA-DRB1*15:01 (P = 1.06 × 10-5) and HLA-DQB1*06:02 (P = 1.78 × 10-6) worked protectively. Logistic regression analysis identified amino acid position 7 in the G-BETA domain of HLA-DRB1 as strongly associated with HAM/TSP (P = 9.52 × 10-10); individuals homozygous for leucine had an associated increased risk of HAM/TSP (odds ratio, 9.57), and proline was protective (odds ratio, 0.65). Both associations were independent of the known risk associated with proviral load. DRB1-GB-7-Leu was not significantly associated with proviral load. We have identified DRB1-GB-7-Leu as a genetic risk factor for HAM/TSP development independent of proviral load. This suggests that the amino acid residue may serve as a specific marker to identify the risk of HAM/TSP even without knowledge of proviral load. In light of its allele frequency worldwide, this biomarker will likely prove useful in HTLV-1 endemic areas across the globe.

3.
Geriatr Gerontol Int ; 21(5): 404-410, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33780140

RESUMO

AIM: The present study aimed to investigate the age-related changes in gait speeds and asymmetry during circular and straight-line gaits among older adults aged 60-79 years. METHODS: The study included 391 community-dwelling older adults aged >60 years, who participated in the Nagahama cohort study. They were assigned to four age groups: 60-64 years (early 60s), 65-69 years (late 60s), 70-74 years (early 70s) and 75-79 years (late 70s). For the circular gait test, the time required to walk twice around a 1-m diameter circle for right and left rotations were measured. The average time of the two trials was measured as the circular gait time, and the side-to-side difference in the circular gait times was calculated as an asymmetry index. Walking speed, asymmetry of step length, and asymmetry of stance duration time during straight-line gait at comfortable and maximal walking pace were measured. RESULTS: Circular gait time in older women in the late 70s group was significantly slower than that in other age groups; however, no age-related change was observed in older men. Maximal gait speeds in the early and late 70s groups were significantly slower than those in the early 60s group. CONCLUSIONS: Age-related decline in circular gait speed was observed in older women aged ≥75 years, but not in older men. Maximal straight-line gait speed decreased significantly in both genders after the age of 70 years. Geriatr Gerontol Int 2021; 21: 404-410.

4.
Artigo em Inglês | MEDLINE | ID: mdl-33606899

RESUMO

OBJECTIVE: To examine the association of low back pain (LBP) and lumbar kyphosis with functional disabilities and knee symptoms in patients with knee osteoarthritis (OA). METHODS: We analyzed 586 participants (80.1% female; age, 68.8 ± 5.2 years) from the Nagahama Study who were aged ≥60 years and had radiographically confirmed knee OA. The Knee Scoring System (KSS) was used to assess functional disabilities and knee symptoms. LBP was defined as the presence of any persistent back pain for more than 3 months. Lumbar kyphosis was determined by skin-surface methods using a computer-aided electronic device called the Spinal Mouse. Multiple linear regression analysis was used for assessing the association of LBP and lumbar kyphosis with the KSS scores. Subgroup analyses based on sex were also performed. RESULTS: LBP and lumbar kyphosis were independently associated with a lower KSS function score after adjustment for covariates (mean difference [95%CI, confidence interval] = -4.96 [-7.56 to -2.36] points for LBP alone, -4.47 [-8.51 to -0.43] points for lumbar kyphosis alone, and -13.86 [-18.86 to -8.86] points for the coexistence of LBP and lumbar kyphosis, respectively). The coexistence of LBP and lumbar kyphosis in women was associated with a lower KSS symptom score (mean difference [95%CI] = -4.49 [-6.42 to -2.55] points). CONCLUSION: These findings suggest that both LBP and lumbar kyphosis are useful clinical signals indicating functional disability and knee symptoms in patients with knee OA.

7.
Respir Res ; 22(1): 6, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407482

RESUMO

BACKGROUND: Chronic sputum production in the general population is historically associated with clinical indices including male sex and smoking history. However, its relationship with gastroesophageal reflux disease (GERD), which may prove an underlying factor in sputum production, is unclear. We aimed to clarify factors associated with sputum production in the general population in cross-sectional and longitudinal manners. METHODS: In the Nagahama study, a community-based cohort study, 9804 subjects were recruited between 2008 and 2010 (baseline assessment), 8293 of whom were followed from 2013 to 2015 (follow-up assessment). This study contained a self-completed questionnaire which included medical history, assessment of sputum production, and a frequency scale for symptoms of GERD. A Frequency Scale for Symptoms of Gastroesophageal Reflux Disease score of ≥ 8 was defined as GERD. In addition to the frequency of sputum production at each assessment, frequency of persistent sputum production defined as sputum production at both assessments was examined. RESULTS: Frequency of sputum production was 32.0% at baseline and 34.5% at follow-up. Multivariable analysis demonstrated that sputum production at baseline was significantly associated with GERD [odds ratio (OR), 1.92; 95% confidence interval (CI) 1.73-2.13] and post-nasal drip (PND) (OR, 2.40; 95% CI 2.15-2.68), independent of other known factors such as older age, male sex and smoking history. These associations between sputum production and GERD or PND were also observed at follow-up. In longitudinal analysis, 19.4% had persistent sputum production and 12.3% had transient sputum production, i.e., at baseline only. Multivariable analysis for risk of persistence of sputum production revealed that persistent sputum production was associated with GERD and PND, in addition to the known risk factors listed above. The proportion of subjects with GERD at both assessments was highest among subjects with persistent sputum production. CONCLUSIONS: Cross-sectional and longitudinal analysis demonstrated an association in the general population between sputum production and GERD, as well as PND, independent of known risk factors. The presence of GERD should be assessed in patients complaining of sputum production.

8.
Clin Rheumatol ; 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33486595

RESUMO

INTRODUCTION/OBJECTIVES: To test the hypothesis that greater extracellular-to-intracellular water (ECW/ICW) ratios in lower-limb muscles are associated with worsened functional abilities in patients with knee osteoarthritis (OA). METHODS: We analyzed data from 787 participants (82.2% female; mean age, 69.6 ± 5.3 years) from the Nagahama Prospective Cohort who were ≥60 years old and had radiographically confirmed bilateral knee OA. The Knee Scoring System (KSS) was used to assess functional abilities. Lower-limb ECW/ICW ratios and skeletal mass index values were determined with multi-frequency bioelectrical impedance analysis (BIA). Multiple linear regression analysis was used to test for associations between ECW/ICW ratios and functional abilities. Subgroup analyses based on OA severities and symptomaticity were also conducted. RESULTS: Increased ECW/ICW ratios were associated with a 4.38-point decrease in the KSS function scores (95% confidence interval [CI], 3.15-5.62 points) after adjusting for covariates. This association varied according to the degree of knee symptoms, especially in individuals with radiologically mild OA. ECW/ICW ratios in individuals with asymptomatic mild OA were associated with a 2.14-point decrease in the KSS function score (95% CI, 0.32-3.96 points), whereas those in individuals with severe symptomatic mild OA were associated with a 6.16-point decrease (95% CI, 2.13-10.19 points). CONCLUSIONS: Our findings indicate that higher ECW/ICW ratios are associated with greater functional disability in patients with knee OA. Therefore, ECW/ICW ratio measurements with multi-frequency BIA can serve as valuable indicators for functional disability in patients with knee OA. Key Points • Higher extracellular-to-intracellular water (ECW/ICW) ratios are associated with greater functional disability levels in patients with knee osteoarthritis (OA). • ECW/ICW ratios are useful clinical signs as a biomarker for poor functional abilities in patients with knee OA.

9.
Sci Adv ; 6(51)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33355142

RESUMO

Rs671 in the aldehyde dehydrogenase 2 gene (ALDH2) is the cause of Asian alcohol flushing response after drinking. ALDH2 detoxifies endogenous aldehydes, which are the major source of DNA damage repaired by the Fanconi anemia pathway. Here, we show that the rs671 defective allele in combination with mutations in the alcohol dehydrogenase 5 gene, which encodes formaldehyde dehydrogenase (ADH5FDH ), causes a previously unidentified disorder, AMeD (aplastic anemia, mental retardation, and dwarfism) syndrome. Cellular studies revealed that a decrease in the formaldehyde tolerance underlies a loss of differentiation and proliferation capacity of hematopoietic stem cells. Moreover, Adh5-/-Aldh2 E506K/E506K double-deficient mice recapitulated key clinical features of AMeDS, showing short life span, dwarfism, and hematopoietic failure. Collectively, our results suggest that the combined deficiency of formaldehyde clearance mechanisms leads to the complex clinical features due to overload of formaldehyde-induced DNA damage, thereby saturation of DNA repair processes.

10.
Ophthalmol Retina ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33309963

RESUMO

PURPOSE: To survey the prevalence and clinical and genetic characteristics of pachydrusen in eyes with central serous chorioretinopathy (CSC) and those of Japanese individuals in the general population. DESIGN: Prospective, observational cohort study. PARTICIPANTS: One thousand thirty-seven Japanese patients were included in this study. Three hundred seven patients (614 eyes) had treatment-naïve CSC without choroidal neovascularization in either eye, whereas 730 individuals (1640 eyes) were Japanese individuals from the general population without explicit ocular diseases. METHODS: Pachydrusen were detected using color fundus photography, and subfoveal choroidal thickness was measured using OCT. Genotypic distributions of 3 single nucleotide polymorphisms, ARMS2 A69S, CFH I62V, and CFH Y402H, were evaluated. MAIN OUTCOME MEASURES: Prevalence of pachydrusen and association with choroidal thickness. RESULTS: The prevalence of pachydrusen was significantly higher among CSC patients than among the general population group (40.1% vs. 15.6%; P < 0.001). Individuals with pachydrusen in either group were significantly older than those without pachydrusen (CSC patients: 62.1 years vs. 48.8 years [P < 0.001]; general individuals: 70.3 years vs. 51.9 years [P < 0.001]). No significant difference was found in subfoveal choroidal thickness between those with and without pachydrusen (CSC patients: 370 µm vs. 375 µm; [P = 0.574]; general population: 297 µm vs. 303 µm [P = 0.521]). However, after adjusting for age, gender, and refractive error, subfoveal choroidal thickness was notably thicker in individuals with pachydrusen than that in individuals without pachydrusen in both groups (P = 0.003 and P = 0.013, respectively). No significant difference was found in genotype distributions between CSC patients with pachydrusen and those without it; whereas, the T allele frequency of ARMS2 A69S was higher in general population individuals with pachydrusen than that in general population individuals without pachydrusen (42.2% vs. 33.9%; P < 0.001; OR, 1.86, adjusted for age, gender, and choroidal thickness). CONCLUSIONS: Pachydrusen was observed more frequently in CSC patients compared with individuals from the general population. In both groups, pachydrusen was associated with a thicker choroid, suggesting that pachydrusen should be considered as a significant sign of pachychoroid.

11.
Sci Rep ; 10(1): 20770, 2020 11 27.
Artigo em Inglês | MEDLINE | ID: mdl-33247286

RESUMO

Next-generation sequencing (NGS) has greatly advanced the studies of causative genes and variants of inherited diseases. While it is sometimes challenging to determine the pathogenicity of identified variants in NGS, the American College of Medical Genetics and Genomics established the guidelines to help the interpretation. However, as to the genetic screenings for patients with retinitis pigmentosa (RP) in Japan, none of the previous studies utilized the guidelines. Considering that EYS is the major causative gene of RP in Japan, we conducted stepwise genetic screening of 220 Japanese patients with RP utilizing the guidelines. Step 1-4 comprised the following, in order: Sanger sequencing for two major EYS founder mutations; targeted sequencing of all coding regions of EYS; whole genome sequencing; Sanger sequencing for Alu element insertion in RP1, a recently determined founder mutation for RP. Among the detected variants, 2, 19, 173, and 1 variant(s) were considered pathogenic and 8, 41, 44, and 5 patients were genetically solved in step 1, 2, 3, and 4, respectively. Totally, 44.5% (98/220) of the patients were genetically solved, and 50 (51.0%) were EYS-associated and 5 (5.1%) were Alu element-associated. Among the unsolved 122 patients, 22 had at least one possible pathogenic variant.

12.
J Hum Genet ; 2020 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-33230199

RESUMO

Human immune systems are very complex, and the basis for individual differences in immune phenotypes is largely unclear. One reason is that the phenotype of the immune system is so complex that it is very difficult to describe its features and quantify differences between samples. To identify the genetic factors that cause individual differences in whole lymphocyte profiles and their changes after vaccination without having to rely on biological assumptions, we performed a genome-wide association study (GWAS), using cytometry data. Here, we applied computational analysis to the cytometry data of 301 people before receiving an influenza vaccine, and 1, 7, and 90 days after the vaccination to extract the feature statistics of the lymphocyte profiles in a nonparametric and data-driven manner. We analyzed two types of cytometry data: measurements of six markers for B cell classification and seven markers for T cell classification. The coordinate values calculated by this method can be treated as feature statistics of the lymphocyte profile. Next, we examined the genetic basis of individual differences in human immune phenotypes with a GWAS for the feature statistics, and we newly identified seven significant and 36 suggestive single-nucleotide polymorphisms associated with the individual differences in lymphocyte profiles and their change after vaccination. This study provides a new workflow for performing combined analyses of cytometry data and other types of genomics data.

13.
Arthritis Res Ther ; 22(1): 280, 2020 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-33246505

RESUMO

BACKGROUND: In knee osteoarthritis (OA), pain is the most frequent and dominant symptom. However, which factors other than radiological changes contribute to the symptoms is unresolved. The aims of this study were to identify factors affecting knee pain from various variables with radiological changes taken into count and exploratively examine what subgroups or phenotype could be identified by cluster analysis using the identified knee pain factors. METHODS: Patients 60 years or older who underwent radiographic evaluation were included in this cross-sectional study, and those subjects who completed a questionnaire about knee symptoms without missing data were eligible for analysis. Multiple regression analysis was used to examine the associations between selected variables and The Japanese Knee Osteoarthritis Measure (JKOM) pain score. We grouped the subjects by cluster analysis using identified variables. RESULTS: Two thousand five hundred forty-two subjects were included in the full set of analyses. Age, body mass index (BMI), radiological grade, bone mineral density (BMD), and high-sensitivity C-reactive protein (hs-CRP) showed a statistically significant correlation with radiological showing the strongest value. For dichotomous variable, presence of depression showed a statistically significant result. We used BMI, radiological grade, BMD, hs-CRP, and presence of depression as a variable for cluster analysis and identified six subgroups: (1) minimal joint disease subgroup, (2) male and high BMD subgroup, (3) high CRP subgroup, (4) severe radiological OA subgroup, (5) depressive subgroup, and (6) moderate radiological OA with high BMI subgroup, showing the worst knee outcome. CONCLUSION: This study identified the factors affecting knee pain other than radiological changes and identified six subgroups of knee outcome in the general population. The results showed that obesity with radiological changes or depression was associated with worse knee outcome.

14.
Sleep Med ; 2020 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-33008732

RESUMO

AIMS: Sleep-disordered breathing (SDB) is a well-known risk factor for cardiovascular outcomes. Studies of patients with SDB have identified frequent night-time urination as a manifestation related to SDB. We aimed to clarify whether night-time frequency of urination is independently associated with SDB in a general population. We also investigated whether night-time frequency of urination can help presumptive diagnose SDB. METHODS: Study participants consisted of 7151 community residents. Oxygen saturation during sleep was measured for four nights using a pulse oximeter. SDB was defined as ≥15 events per hour in which oxygen desaturation exceeded or equal to 3% during an actigraphy-determined sleep period. Night-time frequency of urination was recorded for one week using a sleep diary. RESULTS: Significant positive correlations were evident between night-time frequency of urination and SDB (none, 5.8%; once/night, 14.1%; twice/night, 20.1%; thrice/night, 28.7%; >thrice/night, 44.1%, P < 0.001). This association was independent of possible covariates, including sleep duration (adjusted odds ratio: once/night = 1.50, twice/night = 2.15, thrice/night = 3.07, >thrice/night = 3.73, P < 0.001). Other factors significantly associated with SDB were age, sex, obesity, observation of sleep apnea, and short sleep duration. The area under the curve of the risk score for SDB consisting of these conventional six items (0.834) significantly improved (0.842, P = 0.001) when night-time frequency of urination was considered as a risk score item. CONCLUSION: Night-time frequency of urination was associated with SDB. Our findings suggest that the urination frequency should be considered a manifestation of SDB even in a general population.

15.
Nat Genet ; 52(11): 1169-1177, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33020668

RESUMO

To elucidate the genetics of coronary artery disease (CAD) in the Japanese population, we conducted a large-scale genome-wide association study of 168,228 individuals of Japanese ancestry (25,892 cases and 142,336 controls) with genotype imputation using a newly developed reference panel of Japanese haplotypes including 1,781 CAD cases and 2,636 controls. We detected eight new susceptibility loci and Japanese-specific rare variants contributing to disease severity and increased cardiovascular mortality. We then conducted a trans-ancestry meta-analysis and discovered 35 additional new loci. Using the meta-analysis results, we derived a polygenic risk score (PRS) for CAD, which outperformed those derived from either Japanese or European genome-wide association studies. The PRS prioritized risk factors among various clinical parameters and segregated individuals with increased risk of long-term cardiovascular mortality. Our data improve the clinical characterization of CAD genetics and suggest the utility of trans-ancestry meta-analysis for PRS derivation in non-European populations.

16.
Neurourol Urodyn ; 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33118643

RESUMO

AIM: To evaluate the relationship between nocturia and medical history of nocturnal enuresis: two conditions where diurnal urination rhythm is disturbed. METHODS: The Nagahama study is a longitudinal population-based health survey involving people aged 30-75 years in Nagahama city, Japan. Our analysis included 5,402 participants who completed enuresis and International Prostate Symptom Score questionnaires. Associations between nocturnal enuresis and nocturia were evaluated cross-sectionally and longitudinally with three models: (1) univariate analysis; (2) adjusted for basic characteristics (e.g., age, sex, body mass index, activity, alcohol, and smoking); and (3) adjusted for basic and clinical variables (e.g., hyperglycemia, hyperlipidemia, hypertension, renal insufficiency, insomnia, obstructive sleep apnea, and mental health). RESULTS: In total, 1,613 participants (29.9%) had a medical history of enuresis. The mean night-time frequency was 0.73 at baseline and 0.85 at the 5-year follow-up. The cross-sectional analysis showed participants with a medical history of enuresis had night-time frequency more often than those without this history (0.84 vs. 0.68, p < .0001). Significant differences were observed in Models 2 (p < .0001) and 3 (p < .0001). The longitudinal analysis showed nocturia progression was significantly related to a history of enuresis, with odds ratios of 1.32 (p < .0001) in Model 1, 1.21 (p < .01) in Model 2, and 1.22 (p < .01) in Model 3. CONCLUSIONS: Medical history of enuresis during school age was significantly related to nocturia in adulthood in the cross-sectional analysis, and to progression to nocturia in the longitudinal analysis. These two conditions may possess a common causative association.

17.
J Clin Sleep Med ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32955012

RESUMO

STUDY OBJECTIVES: It is well known that a family history of diabetes (FHD) is a definitive risk factor for type 2 diabetes. It has not been known whether sleep-disordered breathing (SDB) increases the prevalence of diabetes in those with FHD. METHODS: We assessed SDB severity in 7,477 study participants by oximetry corrected by objective sleep duration determined by wrist actigraphy. HbA1c ≥6.5% and/or current medication for diabetes indicated the presence of diabetes. In addition to the overall prevalence, the prevalence of recent-onset diabetes during the almost 5 years before the SDB measurements was investigated. RESULTS: Of the 7,477 participants (mean age 57.9 [range 34.2-80.7, SD 12.1] years, females 67.7%), 1,569 had FHD. The prevalence of diabetes in FHD participants with moderate-to-severe SDB (MS-SDB) was higher than in those without SDB (MS-SDB vs. without SDB: all, 29.3% vs. 3.3%, P <0.001; females, 32.6% vs. 1.9%, P <0.001; males, 26.2% vs. 11.7%, P = 0.037). However, multivariate analysis showed that MS-SDB was significantly associated with a higher prevalence of diabetes only in FHD (+) females (OR [95%CI]: females, 7.43 [3.16-17.45]; males, 0.92 [0.37-2.31]). Among the FHD (+) participants, the prevalence of recent-onset diabetes was higher in those with MS-SDB than those without SDB, but only in females (MS-SDB vs. without SDB: 21.4 % vs. 1.1%, P <0.001). CONCLUSIONS: MS-SDB was associated with diabetes risk in females with FHD, and future studies are needed on whether treatment of SDB in females with FHD would prevent the onset of diabetes.

19.
Ophthalmic Epidemiol ; : 1-7, 2020 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-32924732

RESUMO

PURPOSE: Japan has been known as a super-aged society, and ageing is a well-known risk factor for blinding eye diseases. However, epidemiological studies in ophthalmology are still scarce in Japan, and the sizes of the cohorts are relatively small. "Ganka-Ekigaku Network" (GEN, an acronym for the epidemiological network in ophthalmology in Japanese) is established to develop a capacity to boost each epidemiological study and enrich a potential inter-study collaboration to identify risk factors of visual impairment in aged society. METHODS: We reviewed cohort studies in Japan with the inclusion criteria as: (1) at least n = 1000 at baseline, (2) multiple modalities of ophthalmic data, and (3) diagnosis reviewed by ophthalmologist(s), and (4) ophthalmologists are involved in the investigators group. As of January 2020, GEN includes 4 individual Japanese epidemiological studies namely, Hisayama study, Yamagata Study (Funagata), Tsuruoka Metabolomics Cohort study, and the Nagahama Prospective Genome Cohort for Comprehensive Human Bioscience. RESULTS: GEN includes approximately 25,000 Japanese participants. The baseline surveys started from 1998 to 2012, and since then the data has been prospectively collected approximately every 5 years. A variety of ophthalmic measurements and other factors have been collected in each study in GEN: ophthalmic measurements (fundus photography, optical coherence tomography, etc.), systemic conditions (laboratory data, etc.), and others (DNA, etc.). CONCLUSION: GEN is an open platform for observational ophthalmic epidemiological studies to share standardized methodologies. While each study in GEN pursues specific and original research questions, standardization of the methods will enable us to conduct reliable meta-analysis/pooled data analyses.

20.
Commun Biol ; 3(1): 410, 2020 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-32737415

RESUMO

Keratoconus is a common ocular disorder that causes progressive corneal thinning and is the leading indication for corneal transplantation. Central corneal thickness (CCT) is a highly heritable characteristic that is associated with keratoconus. In this two-stage genome-wide association study (GWAS) of CCT, we identified a locus for CCT, namely STON2 rs2371597 (P = 2.32 × 10-13), and confirmed a significant association between STON2 rs2371597 and keratoconus development (P = 0.041). Additionally, strong STON2 expression was observed in mouse corneal epithelial basal cells. We also identified SMAD3 rs12913547 as a susceptibility locus for keratoconus development using predictive analysis with IBM's Watson question answering computer system (P = 0.001). Further GWAS analyses combined with Watson could effectively reveal detailed pathways underlying keratoconus development.

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