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Genome-wide association study of lung adenocarcinoma in East Asia and comparison with a European population.
Shi, J, Shiraishi, K, Choi, J, Matsuo, K, Chen, TY, Dai, J, Hung, RJ, Chen, K, Shu, XO, Kim, YT, et al
Nature communications. 2023;(1):3043
Abstract
Lung adenocarcinoma is the most common type of lung cancer. Known risk variants explain only a small fraction of lung adenocarcinoma heritability. Here, we conducted a two-stage genome-wide association study of lung adenocarcinoma of East Asian ancestry (21,658 cases and 150,676 controls; 54.5% never-smokers) and identified 12 novel susceptibility variants, bringing the total number to 28 at 25 independent loci. Transcriptome-wide association analyses together with colocalization studies using a Taiwanese lung expression quantitative trait loci dataset (n = 115) identified novel candidate genes, including FADS1 at 11q12 and ELF5 at 11p13. In a multi-ancestry meta-analysis of East Asian and European studies, four loci were identified at 2p11, 4q32, 16q23, and 18q12. At the same time, most of our findings in East Asian populations showed no evidence of association in European populations. In our studies drawn from East Asian populations, a polygenic risk score based on the 25 loci had a stronger association in never-smokers vs. individuals with a history of smoking (Pinteraction = 0.0058). These findings provide new insights into the etiology of lung adenocarcinoma in individuals from East Asian populations, which could be important in developing translational applications.
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Effect of alternate-day fasting on obesity and cardiometabolic risk: A systematic review and meta-analysis.
Park, J, Seo, YG, Paek, YJ, Song, HJ, Park, KH, Noh, HM
Metabolism: clinical and experimental. 2020;:154336
Abstract
BACKGROUND & AIMS Alternate-day fasting (ADF) is related to weight reduction, lowered risks of weight regain, and relative lean body mass preservation compared to continuous energy restriction. This meta-analysis aimed to assess the effects of ADF on obesity-related factors and cardiometabolic risk factors in adults. METHODS Using PubMed, EMBASE, and Cochrane online databases, an electronic search was performed. Randomized controlled trials were investigated to evaluate ADF effects on body mass index (BMI), body weight (BW), waist circumference, body fat mass (FM), lean body mass, and cardiometabolic risk factors in adults aged ≥18 years. By utilizing a random-effects model, meta-analyses to assess weighted mean difference (WMD) with 95% confidence intervals (CIs) were performed for eight randomized controlled trials (total participants = 728). RESULTS We observed significant effects of ADF for BMI (WMD -0.73 kg/m2, 95% CI -1.13 to -0.34), FM (WMD -1.27 kg, 95% CI -2.09 to -0.46), and total cholesterol (WMD -8.14 mg/dL, 95% CI -14.59 to -1.69). Subgroup analyses indicated that significant intervention effects were observed for BMI, BW, FM, and total cholesterol when compared to the control, the participants were overweight, and the study duration was <6 months. ADF is effective in reducing waist circumference in adults aged ≥40 years with obesity. However, there was no difference between ADF and continuous energy restriction, time-restricted feeding, or control with regard to lean body mass. CONCLUSIONS Current evidence suggests that ADF effectively lowers BMI, BW, FM, and total cholesterol in adults with overweight within 6 months compared to the control.
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Diabetic macular oedema: evidence-based treatment recommendations for Asian countries.
Cheung, GC, Yoon, YH, Chen, LJ, Chen, SJ, George, TM, Lai, TY, Park, KH, Tahija, SG, Uy, HS, Wong, TY
Clinical & experimental ophthalmology. 2018;(1):75-86
Abstract
Diabetic macular oedema is the most common cause of diabetic retinopathy-induced vision loss. Efficacy of anti-vascular endothelial growth factor therapy in diabetic macular oedema has been demonstrated in randomized controlled trials. An Asian-specific guideline for diabetic macular oedema treatment is needed as patients in Asia tend to present with far more advanced disease than seen elsewhere in the world. Previous reviews of diabetic macular oedema management lacked a broader assessment of anti-vascular endothelial growth factor treatment choices and newer trials. Recent clinical trial data allow head-to-head comparisons between the different anti-vascular endothelial growth factor agents and treatment regimens. This review aims to summarize the clinical evidence related to various treatment regimens for clinicians, with a focus on anti-vascular endothelial growth factor therapies, and to provide guidance on the treatment of diabetic macular oedema in Asian patients.
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HDL-cholesterol levels and risk of age-related macular degeneration: a multiethnic genetic study using Mendelian randomization.
Fan, Q, Maranville, JC, Fritsche, L, Sim, X, Cheung, CMG, Chen, LJ, Gorski, M, Yamashiro, K, Ahn, J, Laude, A, et al
International journal of epidemiology. 2017;(6):1891-1902
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Abstract
BACKGROUND Dyslipidemia, particularly high-density lipoprotein cholesterol (HDL-C), has recently been implicated in the pathogenesis of age-related macular degeneration (AMD), the leading cause of vision loss. However, epidemiological studies have yielded conflicting results. METHODS We investigated the causal role of plasma lipid levels in AMD in multiethnic populations comprising 16 144 advanced AMD cases and 17 832 controls of European descent, together with 2219 cases and 5275 controls of Asian descent, using Mendelian randomization in three models. Model 1 is a conventional meta-analysis which does not account for pleiotropy of instrumental variable (IV) effects. Model 2 is a univariate, inverse variance weighted regression analysis that accounts for potential unbalanced pleiotropy using MR-Egger method. Finally, Model 3 is a multivariate regression analysis that addresses pleiotropy by MR-Egger method and by adjusting for effects on other lipid traits. RESULTS A 1 standard deviation (SD) higher HDL-cholesterol level was associated with an odds ratio (OR) for AMD of 1.17 (95% confidence interval: 1.07-1.29) in Europeans (P = 6.88 × 10-4) and of 1.58 (1.24-2.00) in Asians (P = 2.92 × 10-4) in Model 3. The corresponding OR estimates were 1.30 (1.09-1.55) in Europeans (P = 3.18 × 10-3) and 1.42 (1.11-1.80) in Asians (P = 4.42 × 10-3) in Model 1, and 1.21 (1.11-1.31) in Europeans (P = 3.12 × 10-5) and 1.51 (1.20-1.91) in Asians (P = 7.61 × 10-4) in Model 2. Conversely, neither LDL-C (Europeans: OR = 0.96, P = 0.272; Asians: OR = 1.02, P = 0.874; Model 3) nor triglyceride levels (Europeans: OR = 0.91, P = 0.102; Asians: OR = 1.06, P = 0.613) were associated with AMD. We also assessed the association between lipid levels and polypoidal choroidal vasculopathy (PCV) in Asians, a subtype of AMD, and found a similar trend for association of PCV with HDL-C levels. CONCLUSIONS Our study shows that high levels of plasma HDL-C are causally associated with an increased risk for advanced AMD in European and Asian populations, implying that strategies reducing HDL-C levels may be useful to prevent and treat AMD.
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Genetic association study of exfoliation syndrome identifies a protective rare variant at LOXL1 and five new susceptibility loci.
Aung, T, Ozaki, M, Lee, MC, Schlötzer-Schrehardt, U, Thorleifsson, G, Mizoguchi, T, Igo, RP, Haripriya, A, Williams, SE, Astakhov, YS, et al
Nature genetics. 2017;(7):993-1004
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Abstract
Exfoliation syndrome (XFS) is the most common known risk factor for secondary glaucoma and a major cause of blindness worldwide. Variants in two genes, LOXL1 and CACNA1A, have previously been associated with XFS. To further elucidate the genetic basis of XFS, we collected a global sample of XFS cases to refine the association at LOXL1, which previously showed inconsistent results across populations, and to identify new variants associated with XFS. We identified a rare protective allele at LOXL1 (p.Phe407, odds ratio (OR) = 25, P = 2.9 × 10-14) through deep resequencing of XFS cases and controls from nine countries. A genome-wide association study (GWAS) of XFS cases and controls from 24 countries followed by replication in 18 countries identified seven genome-wide significant loci (P < 5 × 10-8). We identified association signals at 13q12 (POMP), 11q23.3 (TMEM136), 6p21 (AGPAT1), 3p24 (RBMS3) and 5q23 (near SEMA6A). These findings provide biological insights into the pathology of XFS and highlight a potential role for naturally occurring rare LOXL1 variants in disease biology.
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Meta-analysis of genome-wide association studies identifies multiple lung cancer susceptibility loci in never-smoking Asian women.
Wang, Z, Seow, WJ, Shiraishi, K, Hsiung, CA, Matsuo, K, Liu, J, Chen, K, Yamji, T, Yang, Y, Chang, IS, et al
Human molecular genetics. 2016;(3):620-9
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Abstract
Genome-wide association studies (GWAS) of lung cancer in Asian never-smoking women have previously identified six susceptibility loci associated with lung cancer risk. To further discover new susceptibility loci, we imputed data from four GWAS of Asian non-smoking female lung cancer (6877 cases and 6277 controls) using the 1000 Genomes Project (Phase 1 Release 3) data as the reference and genotyped additional samples (5878 cases and 7046 controls) for possible replication. In our meta-analysis, three new loci achieved genome-wide significance, marked by single nucleotide polymorphism (SNP) rs7741164 at 6p21.1 (per-allele odds ratio (OR) = 1.17; P = 5.8 × 10(-13)), rs72658409 at 9p21.3 (per-allele OR = 0.77; P = 1.41 × 10(-10)) and rs11610143 at 12q13.13 (per-allele OR = 0.89; P = 4.96 × 10(-9)). These findings identified new genetic susceptibility alleles for lung cancer in never-smoking women in Asia and merit follow-up to understand their biological underpinnings.