European integration and the social science of EU studies: the disciplinary politics of a subfield

This article takes the 50th anniversary of the Treaty of Rome as an opportunity to reflect upon half a century of academic discourse about the EU and its antecedents. In particular, it illuminates the theoretical analysis of European integration that has developed within political science and international studies broadly defined. It asks whether it is appropriate to map, as might be tempting, the intellectual 'progress' of the field of study against the empirical evolution of its object (European integration/the EU). The argument to be presented here is that while we can, to some extent, comprehend the evolution of academic thinking about the EU as a reflex to critical shifts in the 'real world' of European integration ('externalist' drivers), it is also necessary to understand 'internalist' drivers of theoretical discourse on European integration/the EU. The article contemplates two such 'internalist' components that have shaped and continue to shape the course of EU studies: scholarly contingency (the fact that scholarship does not proceed with free agency, but is bound by various conditions) and disciplinary politics (the idea that the course of academic work is governed by power games and that there are likely significant disagreements about best practice and progress in a field). In terms of EU studies, the thrust of disciplinary politics tends towards an opposition between 'mainstreaming' and 'pluralist versions' of the political science of EU studies. The final section explores how, in the face of emerging monistic claims about propriety in the field, an effective pluralist political science of the EU might be enhanced

Genomic Standards Consortium projects

© The Author(s), 2014. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Standards in Genomic Sciences 9 (2014): 599-601, doi:10.4056/sigs.5559680.The Genomic Standards Consortium (GSC) is an open-membership community working towards the development, implementation and harmonization of standards in the field of genomics. The mission of the GSC is to improve digital descriptions of genomes, metagenomes and gene marker sequences. The GSC started in late 2005 with the defined task of establishing what is now termed the “Minimum Information about any Sequence” (MIxS) standard [1,2]. As an outgrowth of the activities surrounding the creation and implementation of the MixS standard there are now 18 projects within the GSC [3]. These efforts cover an ever widening range of standardization activities. Given the growth of projects and to promote transparency, participation and adoption the GSC has developed a “GSC Project Description Template”. A complete set of GSC Project Descriptions and the template are available on the GSC website. The GSC has an open policy of participation and continues to welcome new efforts. Any projects that facilitate the standard descriptions and exchange of data are potential candidates for inclusion under the GSC umbrella. Areas that expand the scope of the GSC are encouraged. Through these collective activities we hope to help foster the growth of the ‘bioinformatics standards’ community. For more information on the GSC and its range of projects, please see http://gensc.org/

Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling 6,200 cases and 17,598 controls after replication. We identify nine risk loci at 1p36.11 (rs34676223, P=5.04 × 10−13), 1q42.13 (rs41271473, P=1.06 × 10−10), 4q24 (rs71597109, P=1.37 × 10−10), 4q35.1 (rs57214277, P=3.69 × 10−8), 6p21.31 (rs3800461, P=1.97 × 10−8), 11q23.2 (rs61904987, P=2.64 × 10−11), 18q21.1 (rs1036935, P=3.27 × 10−8), 19p13.3 (rs7254272, P=4.67 × 10−8) and 22q13.33 (rs140522, P=2.70 × 10−9). These new and established risk loci map to areas of active chromatin and show an over-representation of transcription factor binding for the key determinants of B-cell development and immune response

Influence of common genetic variation on lung cancer risk: meta-analysis of 14 900 cases and 29 485 controls

Recent genome-wide association studies (GWASs) have identified common genetic variants at 5p15.33, 6p21-6p22 and 15q25.1 associated with lung cancer risk. Several other genetic regions including variants of CHEK2 (22q12), TP53BP1 (15q15) and RAD52 (12p13) have been demonstrated to influence lung cancer risk in candidate- or pathway-based analyses. To identify novel risk variants for lung cancer, we performed a meta-analysis of 16 GWASs, totaling 14 900 cases and 29 485 controls of European descent. Our data provided increased support for previously identified risk loci at 5p15 (P = 7.2 × 10−16), 6p21 (P = 2.3 × 10−14) and 15q25 (P = 2.2 × 10−63). Furthermore, we demonstrated histology-specific effects for 5p15, 6p21 and 12p13 loci but not for the 15q25 region. Subgroup analysis also identified a novel disease locus for squamous cell carcinoma at 9p21 (CDKN2A/p16INK4A/p14ARF/CDKN2B/p15INK4B/ANRIL; rs1333040, P = 3.0 × 10−7) which was replicated in a series of 5415 Han Chinese (P = 0.03; combined analysis, P = 2.3 × 10−8). This large analysis provides additional evidence for the role of inherited genetic susceptibility to lung cancer and insight into biological differences in the development of the different histological types of lung cance

Fine mapping of chromosome 5p15.33 based on a targeted deep sequencing and high density genotyping identifies novel lung cancer susceptibility loci

Chromosome 5p15.33 has been identified as a lung cancer susceptibility locus, however the underlying causal mechanisms were not fully elucidated. Previous fine-mapping studies of this locus have relied on imputation or investigated a small number of known, common variants. This study represents a significant advance over previous research by investigating a large number of novel, rare variants, as well as their underlying mechanisms through telomere length. Variants for this fine-mapping study were identified through a targeted deep sequencing (average depth of coverage greater than 4000×) of 576 individuals. Subsequently, 4652 SNPs, including 1108 novel SNPs, were genotyped in 5164 cases and 5716 controls of European ancestry. After adjusting for known risk loci, rs2736100 and rs401681, we identified a new, independent lung cancer susceptibility variant in LPCAT1: rs139852726 (OR = 0.46, P = 4.73×10(–9)), and three new adenocarcinoma risk variants in TERT: rs61748181 (OR = 0.53, P = 2.64×10(–6)), rs112290073 (OR = 1.85, P = 1.27×10(–5)), rs138895564 (OR = 2.16, P = 2.06×10(–5); among young cases, OR = 3.77, P = 8.41×10(–4)). In addition, we found that rs139852726 (P = 1.44×10(–3)) was associated with telomere length in a sample of 922 healthy individuals. The gene-based SKAT-O analysis implicated TERT as the most relevant gene in the 5p15.33 region for adenocarcinoma (P = 7.84×10(–7)) and lung cancer (P = 2.37×10(–5)) risk. In this largest fine-mapping study to investigate a large number of rare and novel variants within 5p15.33, we identified novel lung and adenocarcinoma susceptibility loci with large effects and provided support for the role of telomere length as the potential underlying mechanism

Large-scale association analysis identifies new lung cancer susceptibility loci and heterogeneity in genetic susceptibility across histological subtypes.

Although several lung cancer susceptibility loci have been identified, much of the heritability for lung cancer remains unexplained. Here 14,803 cases and 12,262 controls of European descent were genotyped on the OncoArray and combined with existing data for an aggregated genome-wide association study (GWAS) analysis of lung cancer in 29,266 cases and 56,450 controls. We identified 18 susceptibility loci achieving genome-wide significance, including 10 new loci. The new loci highlight the striking heterogeneity in genetic susceptibility across the histological subtypes of lung cancer, with four loci associated with lung cancer overall and six loci associated with lung adenocarcinoma. Gene expression quantitative trait locus (eQTL) analysis in 1,425 normal lung tissue samples highlights RNASET2, SECISBP2L and NRG1 as candidate genes. Other loci include genes such as a cholinergic nicotinic receptor, CHRNA2, and the telomere-related genes OFBC1 and RTEL1. Further exploration of the target genes will continue to provide new insights into the etiology of lung cancer

A communal catalogue reveals Earth’s multiscale microbial diversity

Our growing awareness of the microbial world’s importance and diversity contrasts starkly with our limited understanding of its fundamental structure. Despite recent advances in DNA sequencing, a lack of standardized protocols and common analytical frameworks impedes comparisons among studies, hindering the development of global inferences about microbial life on Earth. Here we present a meta-analysis of microbial community samples collected by hundreds of researchers for the Earth Microbiome Project. Coordinated protocols and new analytical methods, particularly the use of exact sequences instead of clustered operational taxonomic units, enable bacterial and archaeal ribosomal RNA gene sequences to be followed across multiple studies and allow us to explore patterns of diversity at an unprecedented scale. The result is both a reference database giving global context to DNA sequence data and a framework for incorporating data from future studies, fostering increasingly complete characterization of Earth’s microbial diversity