CONAN: copy number variation analysis software for genome-wide association studies

<p>Abstract</p> <p>Background</p> <p>Genome-wide association studies (GWAS) based on single nucleotide polymorphisms (SNPs) revolutionized our perception of the genetic regulation of complex traits and diseases. Copy number variations (CNVs) promise to shed additional light on the genetic basis of monogenic as well as complex diseases and phenotypes. Indeed, the number of detected associations between CNVs and certain phenotypes are constantly increasing. However, while several software packages support the determination of CNVs from SNP chip data, the downstream statistical inference of CNV-phenotype associations is still subject to complicated and inefficient in-house solutions, thus strongly limiting the performance of GWAS based on CNVs.</p> <p>Results</p> <p>CONAN is a freely available client-server software solution which provides an intuitive graphical user interface for categorizing, analyzing and associating CNVs with phenotypes. Moreover, CONAN assists the evaluation process by visualizing detected associations via Manhattan plots in order to enable a rapid identification of genome-wide significant CNV regions. Various file formats including the information on CNVs in population samples are supported as input data.</p> <p>Conclusions</p> <p>CONAN facilitates the performance of GWAS based on CNVs and the visual analysis of calculated results. CONAN provides a rapid, valid and straightforward software solution to identify genetic variation underlying the 'missing' heritability for complex traits that remains unexplained by recent GWAS. The freely available software can be downloaded at <url>http://genepi-conan.i-med.ac.at</url>.</p

Common variation in PHACTR1 is associated with susceptibility to cervical artery dissection

Cervical artery dissection (CeAD), a mural hematoma in a carotid or vertebral artery, is a major cause of ischemic stroke in young adults although relatively uncommon in the general population (incidence of 2.6/100,000 per year). Minor cervical traumas, infection, migraine and hypertension are putative risk factors, and inverse associations with obesity and hypercholesterolemia are described. No confirmed genetic susceptibility factors have been identified using candidate gene approaches. We performed genome-wide association studies (GWAS) in 1,393 CeAD cases and 14,416 controls. The rs9349379[G] allele (PHACTR1) was associated with lower CeAD risk (odds ratio (OR) = 0.75, 95% confidence interval (CI) = 0.69-0.82; P = 4.46 × 10(-10)), with confirmation in independent follow-up samples (659 CeAD cases and 2,648 controls; P = 3.91 × 10(-3); combined P = 1.00 × 10(-11)). The rs9349379[G] allele was previously shown to be associated with lower risk of migraine and increased risk of myocardial infarction. Deciphering the mechanisms underlying this pleiotropy might provide important information on the biological underpinnings of these disabling conditions

On languages on islands

Islands as specific research sites in their own right have been given little direct attention by linguists. The physical segregation, distinctness, and isolation of islands from mainland and continental environments may provide scholars of language with distinct and robust sets of singular and combined case studies for examining the role of islandness in any appreciation of language. Whether distinct and particular sociolinguistic and typological phenomena can be attributable to islands and their islandness and vice versa remains unexplored. This position article considers the possibility of there being anything particular and peculiar about languages spoken on islands as compared to languages spoken on mainlands and continents. It arose out of a workshop titled ‘Exploring island languages’ held at Aarhus University, Denmark on 30 April 2018. The main question posed was: Is there anything special socially, linguistically, grammatically, and typologically about the languages of islands? If so, is it possible to talk about such a thing as an island language?.</p

The dialect dictionary

In this chapter, the making of dialect dictionaries is discussed. We dwell on the user-oriented metalexicographical considerations, and on the ensuing macrostructural and microstructural options. Special attention is devoted to fieldwork procedures for unwritten language varieties. We try and answer the basic questions of field work: What?, Where?, Who?, How? And How much