Common Genetic Variation in Nephrin (NPHS1) and its Associations with Renal and Type 2 Diabetes Mellitus-Related Traits

Master'sMASTER OF SCIENC

Human pharyngeal microbiota in age-related macular degeneration.

BACKGROUND: While the aetiology of age-related macular degeneration (AMD)-a major blinding disease-remains unknown, the disease is strongly associated with variants in the complement factor H (CFH) gene. CFH variants also confer susceptibility to invasive infection with several bacterial colonizers of the nasopharyngeal mucosa. This shared susceptibility locus implicates complement deregulation as a common disease mechanism, and suggests the possibility that microbial interactions with host complement may trigger AMD. In this study, we address this possibility by testing the hypothesis that AMD is associated with specific microbial colonization of the human nasopharynx. RESULTS: High-throughput Illumina sequencing of the V3-V6 region of the microbial 16S ribosomal RNA gene was used to comprehensively and accurately describe the human pharyngeal microbiome, at genus level, in 245 AMD patients and 386 controls. Based on mean and differential microbial abundance analyses, we determined an overview of the pharyngeal microbiota, as well as candidate genera (Prevotella and Gemella) suggesting an association towards AMD health and disease conditions. CONCLUSIONS: Utilizing an extensive study population from Singapore, our results provided an accurate description of the pharyngeal microbiota profiles in AMD health and disease conditions. Through identification of candidate genera that are different between conditions, we provide preliminary evidence for the existence of microbial triggers for AMD. Ethical approval for this study was obtained through the Singapore Health Clinical Institutional Review Board, reference numbers R799/63/2010 and 2010/585/A

DESeq2 differential abundance analysis expressed as Log2FC comparison of AMD-positive samples and control samples.

<p>Negative fold change scores (log2) indicate genera with decreased abundance in AMD-positive samples, and positive fold change scores indicate genera with increased abundance in AMD-positive samples. Each point represents a genus. Genera detected to have significant difference in abundance (<i>Adj-p</i> < 0.05) are shown.</p

Relative abundances of significant genera between 386 controls and 165 individuals with late AMD.

<p>(-) and L-AMD denote controls and late AMD samples respectively. Statistical significance is indicated by (*<i>Adj-p</i> < 0.05), (**<i>Adj-p</i> < 0.005) or (***<i>Adj-p</i> < 0.0005). Mean relative abundances, standard deviations and P-values are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0201768#pone.0201768.s009" target="_blank">S6 Table</a>.</p

Relative abundances of significant genera between 245 case and 386 control samples.

<p>AMD-positive and control samples are denoted by (+) and (-) respectively. Statistical significance is indicated by (*<i>Adj-p</i> < 0.05), (**<i>Adj-p</i> < 0.005) or (***<i>Adj-p</i> < 0.0005). Mean relative abundances, standard deviations and P-values are presented in <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0201768#pone.0201768.s007" target="_blank">S4 Table</a>.</p

Clinical parameters of study subjects.

<p>Clinical parameters of study subjects.</p

Microbial genera significantly associated with high <i>Prevotella</i> relative abundance.

<p>Microbial genera significantly associated with high <i>Prevotella</i> relative abundance.</p

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

Underrepresentation of Asian genomes has hindered population and medical genetics research on Asians, leading to population disparities in precision medicine. By whole-genome sequencing of 4,810 Singapore Chinese, Malays, and Indians, we found 98.3 million SNPs and small insertions or deletions, over half of which are novel. Population structure analysis demonstrated great representation of Asian genetic diversity by three ethnicities in Singapore and revealed a Malay-related novel ancestry component. Furthermore, demographic inference suggested that Malays split from Chinese similar to 24,800 years ago and experienced significant admixture with East Asians similar to 1,700 years ago, coinciding with the Austronesian expansion. Additionally, we identified 20 candidate loci for natural selection, 14 of which harbored robust associations with complex traits and diseases. Finally, we show that our data can substantially improve genotype imputation in diverse Asian and Oceanian populations. These results highlight the value of our data as a resource to empower human genetics discovery across broad geographic regions

Large-Scale Whole-Genome Sequencing of Three Diverse Asian Populations in Singapore

Because of Singapore's unique history of immigration, whole-genome sequence analysis of 4,810 Singaporeans provides a snapshot of the genetic diversity across East, Southeast, and South Asia.</p