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FTO Variants Are Associated With Obesity in the Chinese and Malay Populations in Singapore Jonathan T. Tan 1 , Rajkumar Dorajoo 2 , Mark Seielstad 2 , Xue Ling Sim 1 , Rick Twee-Hee Ong 2 , Kee Seng Chia 1 , Tien Yin Wong 3 4 , Seang Mei Saw 3 5 , Suok Kai Chew 6 , Tin Aung 3 and E-Shyong Tai 1 7 1 Center for Molecular Epidemiology, National University of Singapore, Singapore, Singapore 2 Genome Institute of Singapore, Agency for Science, Technology and Research, Singapore, Singapore 3 Singapore Eye Research Institute, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 4 Centre for Eye Research Australia, University of Melbourne, Melbourne, Australia 5 Department of Community, Occupational and Family Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore 6 Ministry of Health, Singapore, Singapore 7 Department of Endocrinology, Singapore General Hospital, Singapore, Singapore Corresponding author: Tai E. Shyong, eshyong{at}pacific.net.sg Abstract OBJECTIVE— Association between genetic variants at the FTO locus and obesity has been consistently observed in populations of European ancestry and inconsistently in non-Europeans. The aim of this study was to examine the effects of FTO variants on obesity and type 2 diabetes in Southeast Asian populations. RESEARCH DESIGN AND METHODS— We examined associations between nine previously reported FTO single nucleotide polymorphisms (SNPs) with obesity, type 2 diabetes, and related traits in 4,298 participants (2,919 Chinese, 785 Malays, and 594 Asian Indians) from the 1998 Singapore National Health Survey (NHS98) and 2,996 Malays from the Singapore Malay Eye Study (SiMES). RESULTS— All nine SNPs exhibited strong linkage disequilibrium ( r 2 = 0.6–0.99), and minor alleles were associated with obesity in the same direction as previous studies with effect sizes ranging from 0.42 to 0.68 kg/m 2 ( P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m 2 ( P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m 2 ( P < 0.0001) in SiMES Malays after adjustment for age, sex, smoking, alcohol consumption, and exercise. The variants were also associated with type 2 diabetes, though not after adjustment for BMI (with the exception of the SiMES Malays: odds ratio 1.17–1.22; P ≤ 0.026). CONCLUSIONS— FTO variants common among European populations are associated with obesity in ethnic Chinese and Malays in Singapore. Our data do not support the hypothesis that differences in allele frequency or genetic architecture underlie the lack of association observed in some populations of Asian ancestry. Examination of gene-environment interactions involving variants at this locus may provide further insights into the role of FTO in the pathogenesis of human obesity and diabetes. Footnotes Published ahead of print at http://diabetes.diabetesjournals.org on 3 July 2008. J.T.T. and R.D. contributed equally to this study. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Accepted June 19, 2008. Received February 15, 2008. DIABETES

Refractive errors, including myopia, are the most frequent eye disorders worldwide and an increasingly common cause of blindness. This genome-wide association meta-analysis in 160,420 participants and replication in 95,505 participants increased the number of established independent signals from 37 to 161 and showed high genetic correlation between Europeans and Asians (>0.78). Expression experiments and comprehensive in silico analyses identified retinal cell physiology and light processing as prominent mechanisms, and also identified functional contributions to refractive-error development in all cell types of the neurosensory retina, retinal pigment epithelium, vascular endothelium and extracellular matrix. Newly identified genes implicate novel mechanisms such as rod-and-cone bipolar synaptic neurotransmission, anterior-segment morphology and angiogenesis. Thirty-one loci resided in or near regions transcribing small RNAs, thus suggesting a role for post-transcriptional regulation. Our results support the notion that refractive errors are caused by a light-dependent retina-to-sclera signaling cascade and delineate potential pathobiological molecular drivers. Transancestral GWAS meta-analysis in 160,420 individuals identifies 139 loci associated with refractive error, including myopia. Newly identified genes implicate pathways involved in eye growth and light signaling cascades.

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r(2)<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49 × 10(-9) (1.15, 1.10-1.20), 1.45 × 10(-8) (1.13, 1.08-1.18), and 7.14 × 10(-7) (1.13, 1.08-1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS.

Although more than 20 genetic susceptibility loci have been reported for type 2 diabetes (T2D), most reported variants have small to moderate effects and account for only a small proportion of the heritability of T2D, suggesting that the majority of inter-person genetic variation in this disease remains to be determined. We conducted a multistage, genome-wide association study (GWAS) within the Asian Consortium of Diabetes to search for T2D susceptibility markers. From 590,887 SNPs genotyped in 1,019 T2D cases and 1,710 controls selected from Chinese women in Shanghai, we selected the top 2,100 SNPs that were not in linkage disequilibrium (r2<0.2) with known T2D loci for in silico replication in three T2D GWAS conducted among European Americans, Koreans, and Singapore Chinese. The 5 most promising SNPs were genotyped in an independent set of 1,645 cases and 1,649 controls from Shanghai, and 4 of them were further genotyped in 1,487 cases and 3,316 controls from 2 additional Chinese studies. Consistent associations across all studies were found for rs1359790 (13q31.1), rs10906115 (10p13), and rs1436955 (15q22.2) with P-values (per allele OR, 95%CI) of 6.49×10-9 (1.15, 1.10-1.20), 1.45×10-8 (1.13, 1.08-1.18), and 7.14×10-7 (1.13, 1.08-1.19), respectively, in combined analyses of 9,794 cases and 14,615 controls. Our study provides strong evidence for a novel T2D susceptibility locus at 13q31.1 and the presence of new independent risk variants near regions (10p13 and 15q22.2) reported by previous GWAS.

Background Hemifacial spasm (HFS) is a disabling neurological condition. Vascular tortuosity in HFS patients has not been quantified objectively and its relationship with hypertension and posterior fossa volume (PF) is unknown. In a case control magnetic resonance imaging and angiographic (MRI/A) study, we quantified and compared the vascular tortuosity in HFS and controls, and evaluated its relationship with hypertension and PF. Methods Using a commercially available vessel probe tool, an index of tortuosity based on vessel over chord length was employed to quantify vascular tortuosity of the vertebral (VA) and basilar arteries (BA) in 79 subjects (40 HFS, 39 controls). Results The tortuosity index of the BA (1.09 vs 1.16, p  = 0.26, 95 % CI 1.07, 1.23), RVA (1.15 vs 1.15, p  = 0.83, 95 % CI 1.06, 1.38) and LVA (1.14 vs 1.288, p  = 0.16, 95 % CI 1.14, 1.44) was not different between HFS and controls, with adjustments for PF volume and hypertension. Conclusions Contrary to popular belief, our study showed that taking into account hypertension and PF volume, vascular tortuosity of the vertebrobasilar arteries is unlikely to be a major etiologic factor in HFS, though its role in select individuals cannot be excluded. The complex interplay of facial nerve hyperexcitability, genetic predisposition, vascular tortuosity, posterior fossa volume and hypertension needs to be further evaluated.

IntroductionRapid dissemination of findings regarding the Coronavirus Disease 2019 (COVID-19) and its potential effects on pregnancy is crucial to support understanding and development of recommendations for optimization of obstetrics care. However, much of the current studies published are in the form of case reports or case series which can be prone to biases. Other factors also further complicate attempts to analyze data accurately. Hence, this evaluation hopes to highlight some of these problems and provide suggestions to help clinicians mitigate and make reasonable conclusions when reading the abundant yet limited body of evidence when furthering their research efforts.MethodsStudies regarding COVID-19 and pregnancy were searched on databases such as PubMed, EMBASE, Scopus, the Cochrane Library. Manual search of references of select articles were also undertaken. Apart from summarizing study limitations identified by authors, the characteristics of current literature and systematic reviews were also evaluated to identify potential factors affecting accuracy of subsequent analysis.ResultsFactors such as innate biasness in study design of current literature, duplicate reporting, differing inclusion criteria of systematic reviews, scarce data, inadequate follow-up period and limitations of systematic reviews have been shown to hinder the ability for accurate data extrapolation.DiscussionUnless additional studies are conducted in identified areas of data scarcity and a common list of factors affecting accuracy of data analysis are taken into account when developing recommendations, discrepancies will continue to arise and accurate data analysis and valid systematic reviews will be precluded.