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  • Kottyan, Leah C., et al. (author)
  • The IRF5-TNPO3 association with systemic lupus erythematosus has two components that other autoimmune disorders variably share.
  • 2015
  • In: Human Molecular Genetics. - : Oxford University Press (OUP). - 0964-6906 .- 1460-2083. ; 24:2, s. 582-596
  • Journal article (peer-reviewed)abstract
    • Exploiting genotyping, DNA sequencing, imputation and trans-ancestral mapping, we used Bayesian and frequentist approaches to model the IRF5-TNPO3 locus association, now implicated in two immunotherapies and seven autoimmune diseases. Specifically, in systemic lupus erythematosus (SLE), we resolved separate associations in the IRF5 promoter (all ancestries) and with an extended European haplotype. We captured 3230 IRF5-TNPO3 high-quality, common variants across 5 ethnicities in 8395 SLE cases and 7367 controls. The genetic effect from the IRF5 promoter can be explained by any one of four variants in 5.7 kb (P-valuemeta = 6 × 10(-49); OR = 1.38-1.97). The second genetic effect spanned an 85.5-kb, 24-variant haplotype that included the genes IRF5 and TNPO3 (P-valuesEU = 10(-27)-10(-32), OR = 1.7-1.81). Many variants at the IRF5 locus with previously assigned biological function are not members of either final credible set of potential causal variants identified herein. In addition to the known biologically functional variants, we demonstrated that the risk allele of rs4728142, a variant in the promoter among the lowest frequentist probability and highest Bayesian posterior probability, was correlated with IRF5 expression and differentially binds the transcription factor ZBTB3. Our analytical strategy provides a novel framework for future studies aimed at dissecting etiological genetic effects. Finally, both SLE elements of the statistical model appear to operate in Sjögrens syndrome and systemic sclerosis whereas only the IRF5-TNPO3 gene-spanning haplotype is associated with primary biliary cirrhosis, demonstrating the nuance of similarity and difference in autoimmune disease risk mechanisms at IRF5-TNPO3.
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2.
  • Partelow, Stefan, et al. (author)
  • Aquaculture governance : five engagement arenas for sustainability transformation
  • 2023
  • In: Current Opinion in Environmental Sustainability. - 1877-3435 .- 1877-3443. ; 65
  • Journal article (peer-reviewed)abstract
    • A greater focus on governance is needed to facilitate effective and substantive progress toward sustainability transformations in the aquaculture sector. Concerted governance efforts can help move the sector beyond fragmented technical questions associated with intensification and expansion, social and environmental impacts, and toward system-based approaches that address interconnected sustainability issues. Through a review and expert-elicitation process, we identify five engagement arenas to advance a governance agenda for aquaculture sustainability transformation: (1) setting sustainability transformation goals, (2) cross-sectoral linkages, (3) land–water–sea connectivity, (4) knowledge and innovation, and (5) value chains. We then outline the roles different actors and modes of governance can play in fostering sustainability transformations, and discuss action items for researchers, practitioners, and policymakers to operationalize activities within their engagement arenas.
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