Jonathan T. Tan

FTO Variants Are Associated With Obesity in the Chinese and Malay Populations in Singapore

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 (r2 = 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/m2 (P < 0.0001) in NHS98 Chinese, 0.65 to 0.91 kg/m2 (P < 0.02) in NHS98 Malays, and 0.52 to 0.64 kg/m2 (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.

Polymorphisms Identified through Genome-Wide Association Studies and Their Associations with Type 2 Diabetes in Chinese, Malays, and Asian-Indians in Singapore

CONTEXT Novel type 2 diabetes mellitus (T2DM) susceptibility loci, identified through genome-wide association studies (GWAS), have been replicated in many European and Japanese populations. However, the association in other East Asian populations is less well characterized. OBJECTIVE To examine the effects of SNPs in CDKAL1, CDKN2A/B, IGF2BP2, HHEX, SLC30A8, PKN2, LOC387761, and KCNQ1 on risk of T2DM in Chinese, Malays, and Asian-Indians in Singapore. DESIGN We genotyped these candidate single-nucleotide polymorphisms (SNPs) in subjects from three major ethnic groups in Asia, namely, the Chinese (2196 controls and 1541 cases), Malays (2257 controls and 1076 cases), and Asian-Indians (364 controls and 246 cases). We also performed a metaanalysis of our results with published studies in East Asians. RESULTS In Chinese, SNPs in CDKAL1 [odds ratio (OR) = 1.19; P = 2 x 10(-4)], HHEX (OR = 1.15; P = 0.013), and KCNQ1 (OR = 1.21; P = 3 x 10(-4)) were significantly associated with T2DM. Among Malays, SNPs in CDKN2A/B (OR = 1.22; P = 3.7 x 10(-4)), HHEX (OR = 1.12; P = 0.044), SLC30A8 (OR = 1.12; P = 0.037), and KCNQ1 (OR = 1.19-1.25; P = 0.003-2.5 x 10(-4)) showed significant association with T2DM. The combined analysis of the three ethnic groups revealed significant associations between SNPs in CDKAL1 (OR = 1.13; P = 3 x 10(-4)), CDKN2A/B (OR = 1.16; P = 9 x 10(-5)), HHEX (OR = 1.14; P = 6 x 10(-4)), and KCNQ1 (OR = 1.16-1.20; P = 3 x 10(-4) to 3 x 10(-6)) with T2DM. SLC30A8 (OR = 1.06; P = 0.039) showed association only after adjustment for gender and body mass index. Metaanalysis with data from other East Asian populations showed similar effect sizes to those observed in populations of European ancestry. CONCLUSIONS SNPs at T2DM susceptibility loci identified through GWAS in populations of European ancestry show similar effects in Asian populations. Failure to detect these effects across different populations may be due to issues of power owing to limited sample size, lower minor allele frequency, or differences in genetic effect sizes.

Genetic Variation in KCNQ1 Associates With Fasting Glucose andβ-Cell Function A Study of 3,734 Subjects Comprising Three Ethnicities Living in Singapore

OBJECTIVE The potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) has been found through a genome-wide association study to be a strong candidate for conferring susceptibility to type 2 diabetes in East Asian and European populations. Our objective was to describe the association between polymorphisms at the KCNQ1 locus with insulin resistance, beta-cell function, and other type 2 diabetes-related traits in a sample of Chinese, Malays, and Asian Indians living in Singapore. RESEARCH DESIGN AND METHODS We examined the associations between four previously reported KCNQ1 single-nucleotide polymorphisms (SNPs) with type 2 diabetes-related traits in 3,734 participants from the population-based 1998 Singapore National Health Survey cohort (2,520 Chinese, 693 Malay, and 521 Asian Indians). Insulin resistance was calculated from fasting insulin and glucose using the homeostasis model assessment method, whereas pancreatic beta-cell function was assessed using the corrected insulin response at 120 min (CIR(120)). RESULTS SNPs rs2237897, rs2237892, and rs2283228 were significantly associated with type 2 diabetes (odds ratio [OR] 1.48, P = 3 x 10(-4); OR 1.38, P = 0.002; OR 1.31, P = 0.012, respectively). Within the Chinese population, the risk alleles for rs2237897, rs2237892, and rs2283228 were significantly associated with higher fasting glucose levels (P = 0.014, 0.011, and 0.034, respectively) and reduced CIR(120)(P = 0.007, 0.013, and 0.014, respectively). A similar trend was observed among the Malay and Asian Indian minority groups, although this did not reach statistical significance because of limited sample sizes. CONCLUSIONS The increased risk for type 2 diabetes associated with KCNQ1 is likely to be caused by a reduction in insulin secretion. Further studies will be useful to replicate these findings and to fully delineate the role of KCNQ1 and its related pathways in disease pathogenesis.OBJECTIVE The potassium voltage-gated channel, KQT-like subfamily, member 1 (KCNQ1) has been found through a genome-wide association study to be a strong candidate for conferring susceptibility to type 2 diabetes in East Asian and European populations. Our objective was to describe the association between polymorphisms at the KCNQ1 locus with insulin resistance, β-cell function, and other type 2 diabetes–related traits in a sample of Chinese, Malays, and Asian Indians living in Singapore. RESEARCH DESIGN AND METHODS We examined the associations between four previously reported KCNQ1 single-nucleotide polymorphisms (SNPs) with type 2 diabetes–related traits in 3,734 participants from the population-based 1998 Singapore National Health Survey cohort (2,520 Chinese, 693 Malay, and 521 Asian Indians). Insulin resistance was calculated from fasting insulin and glucose using the homeostasis model assessment method, whereas pancreatic β-cell function was assessed using the corrected insulin response at 120 min (CIR120). RESULTS SNPs rs2237897, rs2237892, and rs2283228 were significantly associated with type 2 diabetes (odds ratio [OR] 1.48, P = 3 × 10−4; OR 1.38, P = 0.002; OR 1.31, P = 0.012, respectively). Within the Chinese population, the risk alleles for rs2237897, rs2237892, and rs2283228 were significantly associated with higher fasting glucose levels (P = 0.014, 0.011, and 0.034, respectively) and reduced CIR120(P = 0.007, 0.013, and 0.014, respectively). A similar trend was observed among the Malay and Asian Indian minority groups, although this did not reach statistical significance because of limited sample sizes. CONCLUSIONS The increased risk for type 2 diabetes associated with KCNQ1 is likely to be caused by a reduction in insulin secretion. Further studies will be useful to replicate these findings and to fully delineate the role of KCNQ1 and its related pathways in disease pathogenesis.

A family history of type 2 diabetes is associated with glucose intolerance and obesity-related traits with evidence of excess maternal transmission for obesity-related traits in a South East Asian population

AIM To evaluate family history (FH) of type 2 diabetes (T2DM) as a risk factor for impaired fasting glucose (IFG), impaired glucose tolerance (IGT), T2DM and related metabolic traits in South East Asia and to compare the effects of a paternal versus maternal history. METHODS We studied 4717 men and women (68% Chinese, 18% Malays and 14% Asian Indians) living in Singapore. FH was considered positive if at least one first degree relative had T2DM. Obesity, fasting lipids, glucose and insulin levels were measured for all subjects. Insulin resistance (IR) was estimated by homeostasis model assessment (HOMA). An oral glucose tolerance test was carried for all subjects except those on diabetes medication. RESULTS A positive FH was associated with increased risk of IFG/IGT (OR=1.67, 95% CI=1.42-1.97) and T2DM (OR=2.95, 95% CI=2.36-3.70) as well as higher levels of obesity, HOMA-IR, fasting triglyceride (TG), and lower levels of high density lipoprotein (HDL) cholesterol and HOMA-beta. A maternal history of T2DM appeared to have a greater impact on obesity-related traits than a paternal history of T2DM. Compared to individuals with no FH of T2DM, a maternal history was associated with (i) greater body mass index (BMI) (24.15kg/m(2) vs. 23.42kg/m(2), p=0.016) and waist-to-hip ratio (WHR) (0.874 vs. 0.865, p=0.037) in men; and (ii) greater WHR (0.788 vs. 0.779, p=0.004), fasting triglyceride (1.23mmol/L vs. 1.09mmol/L, p<0.001), HOMA-IR (2.02 vs. 1.75, p<0.001), fasting plasma glucose (5.25mmol/L vs. 5.18mmol/L, p=0.005) and 2-h plasma glucose (6.01mmol/L vs. 5.78mmol/L, p=0.001) and lower HDL-C (1.41mmol/L vs. 1.47mmol/L, p=0.031) in women. CONCLUSION T2DM appears to be heritable in South East Asians with excess maternal transmission of obesity, IR and dyslipidemia.

Next-generation freshwater bioassessment: eDNA metabarcoding with a conserved metazoan primer reveals species-rich and reservoir-specific communities.

Freshwater habitats are of high conservation value and provide a wide range of ecosystem services. Effective management requires regular monitoring. However, conventional methods based on direct observation or specimen collection are so invasive, expensive and labour-intensive that frequent monitoring is uncommon. Here, we test whether the evaluation of environmental DNA (eDNA) from water based on a simple protocol can be used for assessing biodiversity. We use universal metazoan primers for characterizing water eDNA across horizontal and vertical spatial dimensions in two reservoirs with known species diversity for two key taxa. eDNA obtained directly from 42 samples × 15 ml water (total = 630 ml) per reservoir yielded DNA signatures for more than 500 metazoan species, of which 105 could be identified to species/genus based on DNA barcodes. We show that eDNA can be used to assign each water sample to its reservoir of origin, and that eDNA outperforms conventional survey methods in single-sample richness comparisons, while revealing evidence for hundreds of unknown species that are undetected by conventional bioassessment methods. eDNA also confirms the presence of a recently discovered invasive snail species and provides evidence for the continued survival of a rare native species of goby not sighted in that habitat since 2007. eDNA thus promises to be a useful addition to the bioassessment toolbox for freshwater systems.

Retrieving News Stories from a News Integration Archive

The distinctive features of the Bveritas online news integration archive are as follows: 1) automatic clustering of related news documents into themes; 2) organization of these news clusters in a theme map; 3) extraction of meaningful labels for each news cluster; and 4) generation of links to related news articles. Several ways of retrieving news stories from this Bveritas archive are described. The retrieval methods range from the usual query box and links to related stories, to an interactive world map that allows news retrieval by country, to an interactive theme map. Query and browsing are mediated by a Scatter/Gather interface that allows the user to select interesting clusters, out of which the subset of documents are gathered and re-clustered for the user to visually inspect. The user is then asked to select new interesting clusters. This alternating selection/clustering process continues until the user decides to view the individual news story titles.