Refine
Language
- English (3)
Has Fulltext
- yes (3)
Is part of the Bibliography
- no (3)
Keywords
- alleles (1)
- autism spectrum disorder (1)
- autistic disorder (1)
- copy number polymorphism (1)
- genes (1)
- genetics (1)
- genome (1)
- genotype (1)
- genotype determination (1)
- phenotype (1)
Institute
- Medizin (2)
Although autism spectrum disorders (ASDs) have a substantial genetic basis, most of the known genetic risk has been traced to rare variants, principally copy number variants (CNVs). To identify common risk variation, the Autism Genome Project (AGP) Consortium genotyped 1558 rigorously defined ASD families for 1 million single-nucleotide polymorphisms (SNPs) and analyzed these SNP genotypes for association with ASD. In one of four primary association analyses, the association signal for marker rs4141463, located within MACROD2, crossed the genome-wide association significance threshold of P < 5 × 10−8. When a smaller replication sample was analyzed, the risk allele at rs4141463 was again over-transmitted; yet, consistent with the winner's curse, its effect size in the replication sample was much smaller; and, for the combined samples, the association signal barely fell below the P < 5 × 10−8 threshold. Exploratory analyses of phenotypic subtypes yielded no significant associations after correction for multiple testing. They did, however, yield strong signals within several genes, KIAA0564, PLD5, POU6F2, ST8SIA2 and TAF1C.
Modern-day science is under great pressure. A potent mix of increasing expectations, limited resources, tensions between competition and cooperation, and the need for evidence-based funding is creating major change in how science is conducted and perceived. Amidst this 'perfect storm' is the allure of 'research excellence', a concept that drives decisions made by universities and funders, and defines scientists' research strategies and career trajectories. But what is 'excellent' science? And how to recognise it? After decades of inquiry and debate there is still no satisfactory answer. Are we asking the wrong question? Is reality more complex, and 'excellence in science' more elusive, than many are willing to admit? And how should excellence be defined in different parts of the world, particularly in lower-income countries of the 'Global South' where science is expected to contribute to pressing development issues, despite often scarce resources? Many wonder whether the Global South is importing, with or without consenting, the flawed tools for research evaluation from North America and Europe that are not fit for purpose. This book takes a critical view of these issues, touching on conceptual issues and practical problems that inevitably emerge when 'excellence' is at the center of science systems. Emerging from the capacity-building work of the Science Granting Councils Initiative in sub-Saharan Africa, it speaks to scholars, as well as to managers and funders of research around the world. Confronting sticky problems and uncomfortable truths, the chapters contain insights and recommendations that point towards new solutions - both for the Global South and the Global North.
Psoriatic arthritis (PsA) is a chronic inflammatory arthritis associated with psoriasis and, despite the larger estimated heritability for PsA, the majority of genetic susceptibility loci identified to date are shared with psoriasis. Here, we present results from a case-control association study on 1,962 PsA patients and 8,923 controls using the Immunochip genotyping array. We identify eight loci passing genome-wide significance, secondary independent effects at three loci and a distinct PsA-specific variant at the IL23R locus. We report two novel loci and evidence of a novel PsA-specific association at chromosome 5q31. Imputation of classical HLA alleles, amino acids and SNPs across the MHC region highlights three independent associations to class I genes. Finally, we find an enrichment of associated variants to markers of open chromatin in CD8(+) memory primary T cells. This study identifies key insights into the genetics of PsA that could begin to explain fundamental differences between psoriasis and PsA.