A statistical method for region-based meta-analysis of genome-wide association studies in genetically diverse populations.

Genome-wide association studies (GWAS) have become the preferred experimental design in exploring the genetic etiology of complex human traits and diseases. Standard SNP-based meta-analytic approaches have been utilized to integrate the results from multiple experiments. This fundamentally assumes that the patterns of linkage disequilibrium (LD) between the underlying causal variants and the directly genotyped SNPs are similar across the populations for the same SNPs to emerge with surrogate evidence of disease association.

Progression rate of newly diagnosed impaired fasting glycemia to type 2 diabetes mellitus: a study using the National Healthcare Group Diabetes Registry in Singapore.

Background: The aims of the present study were to estimate the rate of progression from newly diagnosed impaired fasting glycemia (IFG) to type 2 diabetes mellitus (T2DM) in Singapore and to identify factors associated with the progression to T2DM in individuals with newly diagnosed IFG.

Methods: The present study was a retrospective cohort study of newly diagnosed IFG from the National Healthcare Group Diabetes Registry between 1 January 2006 and 31 December 2007 to estimated the rate of progression to T2DM. Univariate survival analysis, followed by multivariate survival analysis, was performed and interactions were tested in the final model.

Identification of four novel variants that influence central corneal thickness in multi-ethnic Asian populations.

Central corneal thickness (CCT) is a highly heritable trait. Genes that significantly influence CCT can be candidate genes for common disorders in which CCT has been implicated, such as primary open-angle glaucoma (POAG) and keratoconus. Because the genetic factors controlling CCT in different Asian populations are unclear, we have built on previous work conducted on Singaporean Indians and Malays and extended our hypothesis to individuals of Chinese descent.

Incidence and outcome of male breast cancer: an international population-based study.

Purpose: Male breast cancer is a rare disease with an incidence rate less than 1% of that of female breast cancer. Given its low incidence, few studies have assessed risk and prognosis.

Methods: This population-based study, including 459,846 women and 2,665 men diagnosed with breast cancer in Denmark, Finland, Geneva, Norway, Singapore, and Sweden over the last 40 years, compares trends in incidence, relative survival, and relative excess mortality between the sexes.

SgD-CNV, a database for common and rare copy number variants in three Asian populations.

Copy number variants (CNVs) extend our understanding of the genetic diversity in humans. However, the distribution and characteristics of CNVs in Asian populations remain largely unexplored, especially for rare CNVs that have emerged as important genetic factors for complex traits. In the present study, we performed an in-depth investigation of common and rare CNVs across 8,148 individuals from the three major Asian ethnic groups: Chinese (n = 1,945), Malays (n = 2,399), and Indians (n = 2,217) in Singapore, making this investigation the most comprehensive genome-wide survey of CNVs outside the European-ancestry populations to date.

Genome-wide association study in individuals of South Asian ancestry identifies six new type 2 diabetes susceptibility loci.

We carried out a genome-wide association study of type-2 diabetes (T2D) in individuals of South Asian ancestry. Our discovery set included 5,561 individuals with T2D (cases) and 14,458 controls drawn from studies in London, Pakistan and Singapore. We identified 20 independent SNPs associated with T2D at P < 10(-4) for testing in a replication sample of 13,170 cases and 25,398 controls, also all of South Asian ancestry.

Finally, how histone deacetylase inhibitors disrupt mitosis!

The disruption of normal mitosis by histone deacetylase inhibitors is a significant contributor to the anticancer effects of these drugs. However, the mechanism by which these drugs affect mitosis is poorly understood. A number of recent papers have now thrown considerable light onto how these drugs elicit this very distinctive cell cycle disruption.

Risk factors for pandemic (H1N1) 2009 seroconversion among adults, Singapore, 2009.

A total of 828 community-dwelling adults were studied during the course of the pandemic (H1N1) 2009 outbreak in Singapore during June-September 2009. Baseline blood samples were obtained before the outbreak, and 2 additional samples were obtained during follow-up. Seroconversion was defined as a >4-fold increase in antibody titers to pandemic (H1N1) 2009, determined by using hemagglutination inhibition.

Natural positive selection and north-south genetic diversity in East Asia.

Recent reports have identified a north-south cline in genetic variation in East and South-East Asia, but these studies have not formally explored the basis of these clinical differences. Understanding the origins of these variations may provide valuable insights in tracking down the functional variants in genomic regions identified by genetic association studies. Here we investigate the genetic basis of these differences with genome-wide data from the HapMap, the Human Genome Diversity Project and the Singapore Genome Variation Project.

Non-destructive characterization of structural hierarchy within aligned carbon nanotube assemblies.

Understanding and controlling the hierarchical self-assembly of carbon nanotubes (CNTs) is vital for designing materials such as transparent conductors, chemical sensors, high-performance composites, and microelectronic interconnects. In particular, many applications require high-density CNT assemblies that cannot currently be made directly by low-density CNT growth, and therefore require post-processing by methods such as elastocapillary densification. We characterize the hierarchical structure of pristine and densified vertically aligned multi-wall CNT forests, by combining small-angle and ultra-small-angle x-ray scattering (USAXS) techniques.

Copy number polymorphisms in new HapMap III and Singapore populations.

Copy number variations can be identified using newer genotyping arrays with higher single nucleotide polymorphisms (SNPs) density and copy number probes accompanied by newer algorithms. McCarroll et al. (2008) applied these to the HapMap II samples and identified 1316 copy number polymorphisms (CNPs).

Cancer survival in Singapore, 1993-1997.

The Singapore cancer registry is a national registry established in 1968. Cancer registration is done by passive methods. The registry contributed survival data on 45 cancer sites or types registered during 1993-1997.

Association of variants in FRAP1 and PDGFRA with corneal curvature in Asian populations from Singapore.

Corneal curvature (CC) is a key determinant of major eye diseases, such as keratoconus, myopia and corneal astigmatism. No prior studies have discovered the genes for CC. Here we report the findings from four genome-wide association studies of CC in 10 008 samples from three population groups in Singapore.

A population-based study of copy number variants and regions of homozygosity in healthy Swedish individuals.

The abundance of copy number variants (CNVs) and regions of homozygosity (ROHs) have been well documented in previous studies. In addition, their roles in complex diseases and traits have since been increasingly appreciated. However, only a limited amount of CNV and ROH data is currently available for the Swedish population.

Coffee and tea consumption in relation to inflammation and basal glucose metabolism in a multi-ethnic Asian population: a cross-sectional study.

Background: Higher coffee consumption has been associated with a lower risk of type 2 diabetes in cohort studies, but the physiological pathways through which coffee affects glucose metabolism are not fully understood. The aim of this study was to evaluate the associations between habitual coffee and tea consumption and glucose metabolism in a multi-ethnic Asian population and possible mediation by inflammation.

Methods: We cross-sectionally examined the association between coffee, green tea, black tea and Oolong tea consumption and glycemic (fasting plasma glucose, HOMA-IR, HOMA-beta, plasma HbA1c) and inflammatory (plasma adiponectin and C-reactive protein) markers in a multi-ethnic Asian population (N = 4139).

The Karakiewicz nomogram is the most useful clinical predictor for survival outcomes in patients with localized renal cell carcinoma.

Background: Outcomes after surgical removal of localized renal cell carcinoma (RCC) are variable. There have been multiple prognostic nomograms and risk groups developed for estimation of survival outcomes, with different models in use for evaluating patient eligibility in ongoing trials of adjuvant therapy. The authors aimed to establish the most useful prognostic model for patients with localized RCC to guide trial design, biomarker research, and clinical counseling.

Second malignancies after childhood noncentral nervous system solid cancer: Results from 13 cancer registries.

Children diagnosed with noncentral nervous system solid cancers (NCNSSC) experience several adverse late effects, including second malignant neoplasm. The aim of our study was to assess the risk of specific second malignancies after a childhood NCNSSC. Diagnosis and follow-up data on 10,988 cases of NCNSSC in children (0-14 years) were obtained from 13 registries.

Transferability of type 2 diabetes implicated loci in multi-ethnic cohorts from Southeast Asia.

Recent large genome-wide association studies (GWAS) have identified multiple loci which harbor genetic variants associated with type 2 diabetes mellitus (T2D), many of which encode proteins not previously suspected to be involved in the pathogenesis of T2D. Most GWAS for T2D have focused on populations of European descent, and GWAS conducted in other populations with different ancestry offer a unique opportunity to study the genetic architecture of T2D. We performed genome-wide association scans for T2D in 3,955 Chinese (2,010 cases, 1,945 controls), 2,034 Malays (794 cases, 1,240 controls), and 2,146 Asian Indians (977 cases, 1,169 controls).

Multi-platform segmentation for joint detection of copy number variants.

Motivation: With the expansion of whole-genome studies, there is rapid evolution of genotyping platforms. This leads to practical issues such as upgrading of genotyping equipment which often results in research groups having data from different platforms for the same samples. While having more data can potentially yield more accurate copy-number estimates, combining such data is not straightforward as different platforms show different degrees of attenuation of the true copy-number or different noise characteristics and marker panels.

Synergy between inhibitors of androgen receptor and MEK has therapeutic implications in estrogen receptor-negative breast cancer.

Introduction: Estrogen receptor-negative (ER-) breast cancer is a heterogeneous disease with limited therapeutic options. The molecular apocrine subtype constitutes 50% of ER-tumors and is characterized by overexpression of steroid response genes including androgen receptor (AR). We have recently identified a positive feedback loop between the AR and extracellular signal-regulated kinase (ERK) signaling pathways in the molecular apocrine subtype.

The initial 18 months of the first multi-disciplinary regional Pulmonary Arterial Hypertension Clinic in Australia.

Objective: To report the initial 18 months experience of the first multi-disciplinary regional Pulmonary Arterial Hypertension (PAH) Clinic in Australia.

Design: Prospective cohort study.

Setting: Community setting on the mid-north coast of New South Wales.

Management of blunt traumatic thoracic aorta injuries with endovascular stent-grafts in a tertiary hospital in an urban Asian city.

Background: Thoracic aortic injury from blunt trauma is a life-threatening condition with significant mortality and morbidity with open surgical repair. Endovascular means of treatment is emerging as an attractive and less invasive option. We report our experience with endovascular stent-graft repair for blunt traumatic thoracic aorta injury.

A feedback loop between androgen receptor and ERK signaling in estrogen receptor-negative breast cancer.

Estrogen receptor (ER)-negative breast cancer is heterogeneous, and the biology of this disease has remained poorly understood. Molecular apocrine is a subtype of ER-negative breast cancer that is characterized by the overexpression of steroid-response genes such as AR and a high rate of ErbB2 amplification. In this study, we have identified a positive feedback loop between the AR and extracellular signal-regulated kinase (ERK) signaling pathways in molecular apocrine breast cancer.