Utility of temporal artery biopsy samples for genome-wide analysis of giant cell arteritis

Giant Cell Arteritis (GCA) is the most common vasculitis affecting the elderly. Archived formalin-fixed paraffin-embedded (FFPE) temporal artery biopsy (TAB) specimens potentially represent a valuable resource for large-scale genetic analysis of this disease. FFPE TAB samples were obtained from 12 patients with GCA. Extracted TAB DNA was assessed by real time PCR before restoration using the Illumina HD FFPE Restore Kit. Paired FFPE-blood samples were genotyped on the Illumina OmniExpress FFPE microarray. The FFPE samples that passed stringent quality control measures had a mean genotyping success of >97%. When compared with their matching peripheral blood DNA, the mean discordant heterozygote and homozygote single nucleotide polymorphisms calls were 0.0028 and 0.0003, respectively, which is within the accepted tolerance of reproducibility. This work demonstrates that it is possible to successfully obtain high-quality microarray-based genotypes FFPE TAB samples and that this data is similar to that obtained from peripheral blood.

Making an IMPACT: Campus-wide collaboration for course and learning space transformation

At Purdue University, the Libraries participate in a provost-initiated, campus-wide course redesign program called Instruction Matters: Purdue Academic Course Transformation (IMPACT). This initiative aims to bring active-learning to foundational courses traditionally taught through lectures. Purdue librarians recognized the IMPACT initiative as one way to enter the conversations blooming on our campus about the nature of learning, curriculum design, and how space design impacts potential learning. This article presents three perspectives: 1) the information literacy coordinator, 2) a libraries’ administrator with a gift for space planning, and; 3) an in-the-trenches liaison to course redesign projects. Each discusses the IMPACT initiative from his or her unique perspective and view of its impact on librarian roles. Collectively, the article explains why we think it is essential that this kind of campus effort is supported by libraries.

Genome-wide association analysis identifies 11 risk variants associated with the asthma with hay fever phenotype

Background To date, no genome-wide association study (GWAS) has considered the combined phenotype of asthma with hay fever. Previous analyses of family data from the Tasmanian Longitudinal Health Study provide evidence that this phenotype has a stronger genetic cause than asthma without hay fever. Objective We sought to perform a GWAS of asthma with hay fever to identify variants associated with having both diseases. Methods We performed a meta-analysis of GWASs comparing persons with both physician-diagnosed asthma and hay fever (n = 6,685) with persons with neither disease (n = 14,091). Results At genome-wide significance, we identified 11 independent variants associated with the risk of having asthma with hay fever, including 2 associations reaching this level of significance with allergic disease for the first time: ZBTB10 (rs7009110; odds ratio [OR], 1.14; P = 4 × 10−9) and CLEC16A (rs62026376; OR, 1.17; P = 1 × 10−8). The rs62026376:C allele associated with increased asthma with hay fever risk has been found to be associated also with decreased expression of the nearby DEXI gene in monocytes. The 11 variants were associated with the risk of asthma and hay fever separately, but the estimated associations with the individual phenotypes were weaker than with the combined asthma with hay fever phenotype. A variant near LRRC32 was a stronger risk factor for hay fever than for asthma, whereas the reverse was observed for variants in/near GSDMA and TSLP. Single nucleotide polymorphisms with suggestive evidence for association with asthma with hay fever risk included rs41295115 near IL2RA (OR, 1.28; P = 5 × 10−7) and rs76043829 in TNS1 (OR, 1.23; P = 2 × 10−6). Conclusion By focusing on the combined phenotype of asthma with hay fever, variants associated with the risk of allergic disease can be identified with greater efficiency.

Meta-analysis of genome-wide studies identifies MEF2C SNPs associated with bone mineral density at forearm

Background Forearm fractures affect 1.7 million individuals worldwide each year and most occur earlier in life than hip fractures. While the heritability of forearm bone mineral density (BMD) and fracture is high, their genetic determinants are largely unknown. Aim To identify genetic variants associated with forearm BMD and forearm fractures. Methods BMD at distal radius, measured by dualenergy x-ray absorptiometry, was tested for association with common genetic variants. We conducted a metaanalysis of genome-wide association studies for BMD in 5866 subjects of European descent and then selected the variants for replication in 715 Mexican American samples. Gene-based association was carried out to supplement the single-nucleotide polymorphism (SNP) association test. We then tested the BMD-associated SNPs for association with forearm fracture in 2023 cases and 3740 controls. Results We found that five SNPs in the introns of MEF2C were associated with forearm BMD at a genome-wide significance level (p<5×10-8) in meta-analysis (lead SNP, rs11951031[T] -0.20 SDs per allele, p=9.01×10-9). The gene-based association test suggested an association between MEF2C and forearm BMD ( p=0.003). The association between MEF2C variants and risk of fracture did not achieve statistical significance (SNP rs12521522[A]: OR=1.14 (95% CI 0.92 to 1.35), p=0.14). Meta-analysis also revealed two genome-wide suggestive loci at CTNNA2 and 6q23.2. Conclusions These findings demonstrate that variants at MEF2C were associated with forearm BMD, implicating this gene in the determination of BMD at forearm.

Genome-wide association study of intraocular pressure identifies the GLCCI1/ICA1 region as a glaucoma susceptibility locus

To discover quantitative trait loci for intraocular pressure, amajor risk factor for glaucoma and the only modifiable one,weperformed agenome-wide association studyonadiscoverycohort of2175individualsfromSydney, Australia. We found a novel association between intraocular pressure and a common variant at 7p21 near to GLCCI1 and ICA1. The findings in this region were confirmed through two UK replication cohorts totalling 4866 individuals (rs59072263, Pcombined = 1.10 × 10-8). A copy of the G allele at this SNP is associated with an increase in mean IOP of 0.45 mmHg (95%CI = 0.30-0.61 mmHg). These results lend support to the implication of vesicle trafficking and glucocorticoid inducibility pathways in the determination of intraocular pressure and in the pathogenesis of primary open-angle glaucoma.