A genome-wide association study suggests that a locus within the ataxin 2 binding protein 1 gene is associated with hand osteoarthritis: The Treat-OA consortium

To identify the susceptibility gene in hand osteoarthritis (OA) the authors used a two-stage approach genomewide association study using two discovery samples (the TwinsUK cohort and the Rotterdam discovery subset; a total of 1804 subjects) and four replication samples (the Chingford Study, the Chuvasha Skeletal Aging Study, the Rotterdam replication subset and the Genetics, Arthrosis, and Progression (GARP) Study; a total of 3266 people). Five single-nucleotide polymorphisms (SNPs) had a likelihood of association with hand OA in the discovery stage and one of them (rs716508), was successfully confirmed in the replication stage (meta-analysis p = 1.81×10-5). The C allele conferred a reduced risk of 33% to 41% using a case-control definition. The SNP is located in intron 1 of the A2BP1 gene. This study also found that the same allele of the SNP significantly reduced bone density at both the hip and spine (p<0.01), suggesting the potential mechanism of the gene in hand OA might be via effects on subchondral bone. The authors' findings provide a potential new insight into genetic mechanisms in the development of hand OA

Genome-wide association meta-analysis identifies 48 risk variants and highlights the role of the stria vascularis in hearing loss

Hearing loss is one of the top contributors to years lived with disability and is a risk factor for dementia. Molecular evidence on the cellular origins of hearing loss in humans is growing. Here, we performed a genome-wide association meta-analysis of clinically diagnosed and self-reported hearing impairment on 723,266 individuals and identified 48 significant loci, 10 of which are novel. A large proportion of associations comprised missense variants, half of which lie within known familial hearing loss loci. We used single-cell RNA-sequencing data from mouse cochlea and brain and mapped common-variant genomic results to spindle, root, and basal cells from the stria vascularis, a structure in the cochlea necessary for normal hearing. Our findings indicate the importance of the stria vascularis in the mechanism of hearing impairment, providing future paths for developing targets for therapeutic intervention in hearing loss

Canopy application of film antitranspirants over the reproductive phase enhances yield and yield-related physiological traits of water-stressed oilseed rape (Brassica napus)

Oilseed rape (Brassica napus L.) yield is strongly decreased by water deficit, and crop-management solutions are urgently required considering the emerging difficulties in breeding for drought-tolerant varieties. Film-forming antitranspirants (polymers) are agrochemicals that, applied to the crop canopy, mechanically block the stomata and decrease canopy transpiration. In this study, the drought-protection efficacy of an adaxial-surface application at the flowering stage of two film-forming treatments (poly-1-p-menthene and di-1-p-menthene) was investigated in pot-grown, droughted oilseed rape over two glasshouse experiments. Over the drought period, the two compounds reduced leaf stomatal conductance (P < 0.001), and as the soil moisture deficit increased, they sustained carbon assimilation and improved water-use efficiency with differing efficacy. Following the antitranspirant treatments, ABA concentration in leaves and reproductive organs was severely reduced and this was accompanied by significant improvements in leaf and flower–pod water potential. Drought significantly decreased the seed dry matter production of oilseed rape plants, by 39% on average. The treatments significantly increased seed dry matter by 13% (poly-1-p-menthene) and 17% (di-1-p-menthene), on average, compared with the unsprayed droughted plants, as a result of a significant increase in number of pods per plant, by 11% and 13%, respectively. The results suggest that film-forming compounds may be a useful crop-management tool to avoid severe drought-induced yield losses in oilseed rape by improving water-use efficiency and plant water status, thus alleviating ABA signalling under water deficit

Neck and back pain and intervertebral disc degeneration: Role of occupational factors

Back pain is a near-universal human experience at some time during life, and neck pain is also common. The overwhelming majority flow back and cervical pain is considered to be due to unspecified mechanical factors or disc degeneration, which is a common with ageing and, hence, in people of working age. Back pain and disc disease appear to have significant heritability, based upon twin studies, but environmental factors also contribute - including physical occupational activities in some studies - although the strength of this association remains uncertain. This article examines the contribution of genetic and environmental factors to back pain and disc disease, with a specific focus on occupational exposures. (C) 2011 Elsevier Ltd. All rights reserved

Identification of novel loci associated with hip shape: a meta-analysis of genomewide association studies

Abstract not available.Denis A Baird, Daniel S Evans, Frederick K Kamanu, Jennifer S Gregory, Fiona R Saunders, Claudiu V Giuraniuc, Rebecca J Barr, Richard M Aspden, Deborah Jenkins, Douglas P Kiel, Eric S Orwoll, Steven R Cummings, Nancy E Lane, Benjamin H Mullin, Frances MK Williams, J Brent Richards, Scott G Wilson, Tim D Spector, Benjamin G Faber, Deborah A Lawlor, Elin Grundberg, Claes Ohlsson, Ulrika Pettersson-Kymmer, Terence D Capellini, Daniel Richard, Thomas J Beck, David M Evans, Lavinia Paternoster, David Karasik, and Jonathan H Tobia

Defining the genetic control of human blood plasma N-glycome using genome-wide association study.

Glycosylation is a common post-translational modification of proteins. Glycosylation is associated with a number of human diseases. Defining genetic factors altering glycosylation may provide a basis for novel approaches to diagnostic and pharmaceutical applications. Here we report a genome-wide association study of the human blood plasma N-glycome composition in up to 3811 people measured by Ultra Performance Liquid Chromatography (UPLC) technology. Starting with the 36 original traits measured by UPLC, we computed an additional 77 derived traits leading to a total of 113 glycan traits. We studied associations between these traits and genetic polymorphisms located on human autosomes. We discovered and replicated 12 loci. This allowed us to demonstrate an overlap in genetic control between total plasma protein and IgG glycosylation. The majority of revealed loci contained genes that encode enzymes directly involved in glycosylation (FUT3/FUT6, FUT8, B3GAT1, ST6GAL1, B4GALT1, ST3GAL4, MGAT3 and MGAT5) and a known regulator of plasma protein fucosylation (HNF1A). However, we also found loci that could possibly reflect other more complex aspects of glycosylation process. Functional genomic annotation suggested the role of several genes including DERL3, CHCHD10, TMEM121, IGH and IKZF1. The hypotheses we generated may serve as a starting point for further functional studies in this research area