GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility

The Seattle Care Pathway for securing oral health in older patients

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Диалог. 2012. № 002

Our understanding of the role of freshwaters in the global carbon cycle is being revised, but there is still a lack of data, especially for the cycling of methane, in rivers and streams. Unravelling the role of methanotrophy is key to determining the fate of methane in rivers. Here we focus on the carbon conversion efficiency (CCE) of methanotrophy, that is, how much organic carbon is produced per mole of CH4 oxidised, and how this is influenced by variation in methanotroph communities. First, we show that the CCE of riverbed methanotrophs is consistently high (~50%) across a wide range of methane concentrations (~10–7000 nM) and despite a 10-fold span in the rate of methane oxidation. Then, we show that this high conversion efficiency is largely conserved (50%± confidence interval 44–56%) across pronounced variation in the key functional gene (70 operational taxonomic units (OTUs)), particulate methane monooxygenase (pmoA), and marked shifts in the abundance of Type I and Type II methanotrophs in eight replicate chalk streams. These data may suggest a degree of functional redundancy within the variable methanotroph community inhabiting these streams and that some of the variation in pmoA may reflect a suite of enzymes of different methane affinities which enables such a large range of methane concentrations to be oxidised. The latter, coupled to their high CCE, enables the methanotrophs to sustain net production throughout the year, regardless of the marked temporal and spatial changes that occur in methane