Karolinska Institutet

About: Karolinska Institutet is a education organization based out in Stockholm, Sweden. It is known for research contribution in the topics: Population & Poison control. The organization has 46212 authors who have published 121142 publications receiving 6008130 citations.

Inparanoid: a comprehensive database of eukaryotic orthologs.

Abstract: The Inparanoid eukaryotic ortholog database (http:// inparanoid.cgb.ki.se/)isacollectionofpairwiseortholog groups between 17 whole genomes; Anopheles gambiae, Caenorhabditis briggsae, Caenorhabditis elegans, Drosophila melanogaster, Danio rerio, Takifugu rubripes, Gallus gallus, Homo sapiens, Mus musculus, Pan troglodytes, Rattus norvegicus, Oryza sativa, Plasmodium falciparum, Arabidopsis thaliana,Escherichia coli,Saccharomyces cerevisiae and Schizosaccharomyces pombe. Complete proteomes for these genomes were derived from Ensembl and UniProt and compared pairwise using Blast, followed by a clustering step using the Inparanoid program. An Inparanoid cluster is seeded by areciprocally best-matching ortholog pair, around which inparalogs (should they exist) are gathered independently, while outparalogs are excluded. The ortholog clusters can be searched on the website using Ensembl gene/protein or UniProt identifiers, annotation text or by Blast alignment against our protein datasets. The entire dataset can be downloaded, as can the Inparanoid program itself.

Diabetes mellitus and risk of breast cancer: a meta-analysis.

Abstract: Diabetes mellitus has been associated with an increased risk of several types of cancers, but its relationship with breast cancer remains unclear. We conducted a meta-analysis of case-control and cohort studies to assess the evidence regarding the association between diabetes and risk of breast cancer. Studies were identified by searching MEDLINE (1966-February 2007) and the references of retrieved articles. We identified 20 studies (5 case-control and 15 cohort studies) that reported relative risk (RR) estimates (odds ratio, rate ratio/hazard ratio, or standardized incidence ratio) with 95% confidence intervals (CIs) for the relation between diabetes (largely Type II diabetes) and breast cancer incidence. Summary RRs were calculated using a random-effects model. Analysis of all 20 studies showed that women with (versus without) diabetes had a statistically significant 20% increased risk of breast cancer (RR, 1.20; 95% CI, 1.12-1.28). The summary estimates were similar for case-control studies (RR, 1.18; 95% CI, 1.05-1.32) and cohort studies (RR, 1.20; 95% CI, 1.11-1.30). Meta-analysis of 5 cohort studies on diabetes and mortality from breast cancer yielded a summary RR of 1.24 (95% CI, 0.95-1.62) for women with (versus without) diabetes. Findings from this meta-analysis indicate that diabetes is associated with an increased risk of breast cancer.

A regulatory polymorphism in PDCD1 is associated with susceptibility to systemic lupus erythematosus in humans

Abstract: Systemic lupus erythematosus (SLE, OMIM 152700) is a complex autoimmune disease that affects 0.05% of the Western population, predominantly women. A number of susceptibility loci for SLE have been suggested in different populations, but the nature of the susceptibility genes and mutations is yet to be identified. We previously reported a susceptibility locus (SLEB2) for Nordic multi-case families. Within this locus, the programmed cell death 1 gene (PDCD1, also called PD-1) was considered the strongest candidate for association with the disease. Here, we analyzed 2,510 individuals, including members of five independent sets of families as well as unrelated individuals affected with SLE, for single-nucleotide polymorphisms (SNPs) that we identified in PDCD1. We show that one intronic SNP in PDCD1 is associated with development of SLE in Europeans (found in 12% of affected individuals versus 5% of controls; P = 0.00001, r.r. (relative risk) = 2.6) and Mexicans (found in 7% of affected individuals versus 2% of controls; P = 0.0009, r.r. = 3.5). The associated allele of this SNP alters a binding site for the runt-related transcription factor 1 (RUNX1, also called AML1) located in an intronic enhancer, suggesting a mechanism through which it can contribute to the development of SLE in humans.

Contribution of copy number variants to schizophrenia from a genome-wide study of 41,321 subjects

Abstract: Copy number variants (CNVs) have been strongly implicated in the genetic etiology of schizophrenia (SCZ). However, genome-wide investigation of the contribution of CNV to risk has been hampered by limited sample sizes. We sought to address this obstacle by applying a centralized analysis pipeline to a SCZ cohort of 21,094 cases and 20,227 controls. A global enrichment of CNV burden was observed in cases (odds ratio (OR) = 1.11, P = 5.7 × 10-15), which persisted after excluding loci implicated in previous studies (OR = 1.07, P = 1.7 × 10-6). CNV burden was enriched for genes associated with synaptic function (OR = 1.68, P = 2.8 × 10-11) and neurobehavioral phenotypes in mouse (OR = 1.18, P = 7.3 × 10-5). Genome-wide significant evidence was obtained for eight loci, including 1q21.1, 2p16.3 (NRXN1), 3q29, 7q11.2, 15q13.3, distal 16p11.2, proximal 16p11.2 and 22q11.2. Suggestive support was found for eight additional candidate susceptibility and protective loci, which consisted predominantly of CNVs mediated by nonallelic homologous recombination.