Elevated serum leptin, adiponectin and leptin to adiponectin ratio is associated with chronic kidney disease in Asian adults.

Background: Adiponectin and leptin, two of the key cytokines secreted by adipocytes, have been shown to be associated with cardiovascular disease. However, the association of these adipocytokines with chronic kidney disease (CKD) is not clear. We examined the association of serum adiponectin, leptin levels and leptin to adiponectin ratio (LAR) with CKD in a population-based sample of Asian adults.

Aggregate Effects of Intraocular Pressure and Cup-to-Disc Ratio Genetic Variants on Glaucoma in a Multiethnic Asian Population.

Purpose: High intraocular pressure (IOP) and large vertical cup-to-disc ratio (VCDR) are important risk factors of glaucoma. Recent genome-wide association studies have discovered several genetic variants associated with IOP and VCDR. In this study, we examined the aggregate effects of these IOP-, VCDR-associated variants on glaucoma.

Relationship between measured average glucose by continuous glucose monitor and HbA1c measured by three different routine laboratory methods.

Objectives: The relationship between glycated hemoglobin A1c (HbA1c) and average glucose has been described by the empirically derived estimated average glucose (eAG) equation in the A1c-Derived Average Glucose (ADAG) study, with extensive calibration efforts in four secondary reference HbA1c methods. It is not known if this relationship is preserved when HbA1c is measured by routine laboratory methods under routine conditions.

Design And Methods: We measured average glucose (mAG) by six days of continuous glucose monitoring in 45 adults with stable HbA1c (<1% HbA1c change in the preceding two months).

Factors associated with psychological distress, behavioral impact and health-related quality of life among patients with type 2 diabetes mellitus.

Background: Data on psychological distress (DIS), behavioral impact (BI) and health-related quality of life (HRQoL) are important yet lacking among Asian patients with Type 2 diabetes mellitus (T2DM). We aim to identify factors associated with DIS, BI and HRQoL among T2DM to better understand patient needs.

Methods: DIS was measured with Diabetes Health Profile (DHP-18) Psychological Distress (DHP-PD) subscale, Problem Areas in Diabetes (PAID) and Kessler-10 (K10), BI with DHP-18 Barriers to Activity and Disinhibited Eating subscales and HRQoL with Audit of Diabetes-Dependent Quality of Life.

Retinal microvascular abnormalities and risk of renal failure in Asian populations.

Background: Retinal microvascular signs may provide insights into the structure and function of small vessels that are associated with renal disease. We examined the relationship of retinal microvascular signs with both prevalent and incident end-stage renal disease (ESRD) in a multi-ethnic Asian population.

Methods: A total of 5763 subjects (aged ≥ 40 years) from two prospective population-based studies (the Singapore Malay Eye Study and the Singapore Prospective Study) were included for the current analysis.

Low-frequency and rare exome chip variants associate with fasting glucose and type 2 diabetes susceptibility.

Fasting glucose and insulin are intermediate traits for type 2 diabetes. Here we explore the role of coding variation on these traits by analysis of variants on the HumanExome BeadChip in 60,564 non-diabetic individuals and in 16,491 T2D cases and 81,877 controls. We identify a novel association of a low-frequency nonsynonymous SNV in GLP1R (A316T; rs10305492; MAF=1.

New loci and coding variants confer risk for age-related macular degeneration in East Asians.

Age-related macular degeneration (AMD) is a major cause of blindness, but presents differently in Europeans and Asians. Here, we perform a genome-wide and exome-wide association study on 2,119 patients with exudative AMD and 5,691 controls, with independent replication in 4,226 patients and 10,289 controls, all of East Asian descent, as part of The Genetics of AMD in Asians (GAMA) Consortium. We find a strong association between CETP Asp442Gly (rs2303790), an East Asian-specific mutation, and increased risk of AMD (odds ratio (OR)=1.

Establishing the thematic framework for a diabetes-specific health-related quality of life item bank for use in an english-speaking asian population.

Aims: To establish a thematic framework for a Diabetes Mellitus (DM)-specific health-related quality of life (HRQoL) item bank by identifying important HRQoL themes and content gaps in existing DM-specific HRQoL measures and determining whether Patient-Reported Outcomes Measurement Information System (PROMIS) item banks are useful as a starting point.

Methodology: English-speaking Type 2 DM patients were recruited from an outpatient specialist clinic in Singapore. Thematic analysis was performed through open coding and axial coding.

Relationship of systemic endothelial function and peripheral arterial stiffness with diabetic retinopathy.

Background: To investigate possible associations between diabetic retinopathy (DR) and systemic vascular endothelial function and arterial stiffness measured using reactive hyperaemia peripheral arterial tonometry.

Methods: This was a cross-sectional observational clinical study. Subjects with diabetes were recruited and DR was graded from retinal photographs.

A novel splice-site mutation in ALS2 establishes the diagnosis of juvenile amyotrophic lateral sclerosis in a family with early onset anarthria and generalized dystonias.

The diagnosis of childhood neurological disorders remains challenging given the overlapping clinical presentation across subgroups and heterogeneous presentation within subgroups. To determine the underlying genetic cause of a severe neurological disorder in a large consanguineous Pakistani family presenting with severe scoliosis, anarthria and progressive neuromuscular degeneration, we performed genome-wide homozygosity mapping accompanied by whole-exome sequencing in two affected first cousins and their unaffected parents to find the causative mutation. We identified a novel homozygous splice-site mutation (c.

Forecasting the burden of type 2 diabetes in Singapore using a demographic epidemiological model of Singapore.

Objective: Singapore is a microcosm of Asia as a whole, and its rapidly ageing, increasingly sedentary population heralds the chronic health problems other Asian countries are starting to face and will likely face in the decades ahead. Forecasting the changing burden of chronic diseases such as type 2 diabetes in Singapore is vital to plan the resources needed and motivate preventive efforts.

Methods: This paper describes an individual-level simulation model that uses evidence synthesis from multiple data streams-national statistics, national health surveys, and four cohort studies, and known risk factors-aging, obesity, ethnicity, and genetics-to forecast the prevalence of type 2 diabetes in Singapore.

Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci.

Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns.

Associations between disease awareness and health-related quality of life in a multi-ethnic Asian population.

Background: Health related quality of life (HRQoL) is an important dimension of individuals' well-being, and especially in chronic diseases like diabetes and hypertension. The objective of this study was to evaluate the contributions of disease process, comorbidities, medication or awareness of the disease to HRQoL in diabetes mellitus, hypertension and dyslipidemia.

Methods: This was a cross-sectional study of 3514 respondents from the general community in Singapore, assessed for HRQoL, disease and comorbid conditions through self-report, clinical and laboratory investigations.

Diagnosis of diabetes mellitus using HbA1c in Asians: relationship between HbA1c and retinopathy in a multiethnic Asian population.

Context: Hemoglobin A1c (HbA1c) ≥ 6.5% (47.5 mmol/mol) has recently been included as a criterion for the diagnosis of diabetes mellitus.

Allele frequencies of variants in ultra conserved elements identify selective pressure on transcription factor binding.

Ultra-conserved genes or elements (UCGs/UCEs) in the human genome are extreme examples of conservation. We characterized natural variations in 2884 UCEs and UCGs in two distinct populations; Singaporean Chinese (n = 280) and Italian (n = 501) by using a pooled sample, targeted capture, sequencing approach. We identify, with high confidence, in these regions the abundance of rare SNVs (MAF<0.

Genome-wide association study for refractive astigmatism reveals genetic co-determination with spherical equivalent refractive error: the CREAM consortium.

To identify genetic variants associated with refractive astigmatism in the general population, meta-analyses of genome-wide association studies were performed for: White Europeans aged at least 25 years (20 cohorts, N = 31,968); Asian subjects aged at least 25 years (7 cohorts, N = 9,295); White Europeans aged <25 years (4 cohorts, N = 5,640); and all independent individuals from the above three samples combined with a sample of Chinese subjects aged <25 years (N = 45,931). Participants were classified as cases with refractive astigmatism if the average cylinder power in their two eyes was at least 1.00 diopter and as controls otherwise.

Metabolic syndrome and risk of age-related macular degeneration.

Purpose: To investigate the relationship between metabolic syndrome (MetS) and its components with the risk of early- and late-stage age-related macular degeneration (AMD).

Methods: A prospective cohort of individuals aged older than or equal to 49 years were followed up over a period of 10 years in the Blue Mountains Eye Study, Australia. MetS components were measured at baseline (1992-1994), 5-year (1997-1999), and 10-year (2002-2004) follow-ups.

Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study.

Purpose: Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci.

Methods: Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism (SNPs).

Genome-wide association meta-analysis identifies novel variants associated with fasting plasma glucose in East Asians.

Fasting plasma glucose (FPG) has been recognized as an important indicator for the overall glycemic state preceding the onset of metabolic diseases. So far, most indentified genome-wide association loci for FPG were derived from populations with European ancestry, with a few exceptions. To extend a thorough catalog for FPG loci, we conducted meta-analyses of 13 genome-wide association studies in up to 24,740 nondiabetic subjects with East Asian ancestry.

Genome-wide analysis of multi-ancestry cohorts identifies new loci influencing intraocular pressure and susceptibility to glaucoma.

Elevated intraocular pressure (IOP) is an important risk factor in developing glaucoma, and variability in IOP might herald glaucomatous development or progression. We report the results of a genome-wide association study meta-analysis of 18 population cohorts from the International Glaucoma Genetics Consortium (IGGC), comprising 35,296 multi-ancestry participants for IOP. We confirm genetic association of known loci for IOP and primary open-angle glaucoma (POAG) and identify four new IOP-associated loci located on chromosome 3q25.

Dynamic responses in retinal vessel caliber with flicker light stimulation in eyes with diabetic retinopathy.

Purpose: This study investigated the responses of retinal vessels to flickering light in diabetic patients with various stages of diabetic retinopathy (DR).

Methods: This cross-sectional observational study evaluated adult subjects with diabetes mellitus. The Dynamic Vessel Analyzer (DVA) was used to measure retinal vascular dilatation in response to diffuse illuminance flicker.