8 research outputs found
Meta-analysis of type 2 Diabetes in African Americans Consortium
Type 2 diabetes (T2D) is more prevalent in African Americans than in Europeans. However, little is known about the genetic risk in African Americans despite the recent identification of more than 70 T2D loci primarily by genome-wide association studies (GWAS) in individuals of European ancestry. In order to investigate the genetic architecture of T2D in African Americans, the MEta-analysis of type 2 DIabetes in African Americans (MEDIA) Consortium examined 17 GWAS on T2D comprising 8,284 cases and 15,543 controls in African Americans in stage 1 analysis. Single nucleotide polymorphisms (SNPs) association analysis was conducted in each study under the additive model after adjustment for age, sex, study site, and principal components. Meta-analysis of approximately 2.6 million genotyped and imputed SNPs in all studies was conducted using an inverse variance-weighted fixed effect model. Replications were performed to follow up 21 loci in up to 6,061 cases and 5,483 controls in African Americans, and 8,130 cases and 38,987 controls of European ancestry. We identified three known loci (TCF7L2, HMGA2 and KCNQ1) and two novel loci (HLA-B and INS-IGF2) at genome-wide significance (4.15 × 10(-94)<P<5 × 10(-8), odds ratio (OR) = 1.09 to 1.36). Fine-mapping revealed that 88 of 158 previously identified T2D or glucose homeostasis loci demonstrated nominal to highly significant association (2.2 × 10(-23) < locus-wide P<0.05). These novel and previously identified loci yielded a sibling relative risk of 1.19, explaining 17.5% of the phenotypic variance of T2D on the liability scale in African Americans. Overall, this study identified two novel susceptibility loci for T2D in African Americans. A substantial number of previously reported loci are transferable to African Americans after accounting for linkage disequilibrium, enabling fine mapping of causal variants in trans-ethnic meta-analysis studies.Peer reviewe
Mixed data types and the use of pattern analysis on the Australian groundnut germplasm data
Data in germplasm collections contain a mixture of data types; binary, multistate and quantitative. Given the multivariate nature of these data, the pattern analysis methods of classification and ordination have been identified as suitable techniques for statistically evaluating the available diversity. The proximity (or resemblance) measure, which is in part the basis of the complementary nature of classification and ordination techniques, is often specific to particular data types. The use of a combined resemblance matrix has an advantage over data type specific proximity measures. This measure accommodates the different data types without manipulating them to be of a specific type. Descriptors are partitioned into their data types and an appropriate proximity measure is used on each. The separate proximity matrices, after range standardisation, are added as a weighted average and the combined resemblance matrix is then used for classification and ordination