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

Pre-reading format and learner proficiency level in L2 reading comprehension

The article describes two related experiments into the effect of pre‐reading on the text comprehension of a population of L2 learners at three proficiency levels. Four sets of pre‐reading materials were used, two in each experiment. All were geared to content‐schemata activation, but differed in terms of the type of stimulus provided. The materials used in experiment I (a text summary and a set of pre‐questions) involved the provision of a relatively elaborated set of interpretive cues; those used in experiment II (topic prediction and a vocabulary‐based task) were more open and allowed for a greater degree of learner‐based schemata activation. Two main lines of investigation were pursued: the first relates to the relative effectiveness of the different pre‐reading formats, and the second to the possibility of an interaction between pre‐reading format and L2 proficiency level. Results indicated the more constraining, schemata‐provision formats used in experiment I to be more effective as aids to text comprehension. No level‐treatment interaction was observed, though comprehension facilitation was observed only among the lower proficiency groups — the higher proficiency group deriving no benefit from any of the pre‐reading formats used. Copyright © 1990, Wiley Blackwell. All rights reservedSCOPUS: ar.jFLWNAinfo:eu-repo/semantics/publishe

A comparative study of the effect of two pre-reading formats on L2 reading comprehension

The article reports on a study of the effect of two pre-reading formats, a text summary and a set of pre-questions, on the text com prehension of a population of L2 learners at three proficiency levels. Two main points were investigated — the overall facilitative poten tial of the two treatments and the possible interaction of L2 profi ciency with pre-reading treatment. Both treatments produced com prehension facilitation with lower proficiency groups but not with the more advanced group. Levels of facilitation were similar for the two treatments, though the summary showed a consistent but limited lead over the pre-questions. No significant level-treatment interac tion emerged. The results are discussed in relation to the use of pre- reading in L2 comprehension development. © 1988, Sage Publications. All rights reserved.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Type I antithrombin deficiency: five novel mutations associated with thrombosis

The genetic basis of Type I antithrombin deficiency has been investigated in six unrelated kindred with positive histories of thrombosis using a PCR amplification/direct sequencing approach. Four frameshift mutations, all introducing premature translation termination codons were identified. Thus, deletions, of a C at nucleotide position 2599 or 2600, a G at position 2601-2602 and a CT dinucleotide at position 7428-7429 were detected in three kindred and confirmed by restriction enzyme analysis. The identical insertion, of a T at nucleotide 2770, was observed in two apparently unrelated families. This finding may have been due to a founder effect since antithrombin gene polymorphism analysis showed all affected individuals to share a common haplotype. An in frame deletion of 6 bp at nucleotide position 2690-2696 causing the removal of codons 76 and 77 encoding Ile 76 and Phe 77 was also detected indicating that these amino acids are essential for stability of the mature antithrombin

Antithrombin cambridge II (Ala384Ser): clinical, functional and haplotype analysis of 18 families

Thirty-one individuals from 18 unrelated families with antithrombin deficiency have been identified as having a single point mutation within codon 384 (13268 GCA→TCA) resulting in an alanine to serine substitution. Six families (11 individuals) were identified by the screening of individuals with thromboembolic disease or with a family history of thromboembolic disease, whilst the remaining 12 families (20 individuals) were identified by screening of asymptomatic blood donors. Four individuals had a history of venous thrombotic disease, a further 2 gave a history of superficial thrombophlebitis but the remaining 25 individuals were asymptomatic. Affected individuals demonstrated normal immunological levels of antithrombin but a decrease in anti-IIa activity in the presence of heparin. Haplotype analysis was used to examine the possibility of a founder effect to explain the high frequency of this non-CpG mutation. 29/31 individuals showed a single common “core” haplotype, the only variation existing in the number of copies of an (ATT)n repeat polymorphism – 13, 14, 15 or 17. The results suggest that at most there are four independent origins for this mutation