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- Saevarsdottir, S., et al.
(författare)
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Multiomics analysis of rheumatoid arthritis yields sequence variants that have large effects on risk of the seropositive subset
- 2022
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Ingår i: Annals of the Rheumatic Diseases. - : BMJ. - 0003-4967 .- 1468-2060. ; 81:8
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Tidskriftsartikel (refereegranskat)abstract
- Objectives To find causal genes for rheumatoid arthritis (RA) and its seropositive (RF and/or ACPA positive) and seronegative subsets. Methods We performed a genome-wide association study (GWAS) of 31 313 RA cases (68% seropositive) and similar to 1 million controls from Northwestern Europe. We searched for causal genes outside the HLA-locus through effect on coding, mRNA expression in several tissues and/or levels of plasma proteins (SomaScan) and did network analysis (Qiagen). Results We found 25 sequence variants for RA overall, 33 for seropositive and 2 for seronegative RA, altogether 37 sequence variants at 34 non-HLA loci, of which 15 are novel. Genomic, transcriptomic and proteomic analysis of these yielded 25 causal genes in seropositive RA and additional two overall. Most encode proteins in the network of interferon-alpha/beta and IL-12/23 that signal through the JAK/STAT-pathway. Highlighting those with largest effect on seropositive RA, a rare missense variant in STAT4 (rs140675301-A) that is independent of reported non-coding STAT4-variants, increases the risk of seropositive RA 2.27-fold (p=2.1x10(-9)), more than the rs2476601-A missense variant in PTPN22 (OR=1.59, p=1.3x10(-160)). STAT4 rs140675301-A replaces hydrophilic glutamic acid with hydrophobic valine (Glu128Val) in a conserved, surface-exposed loop. A stop-mutation (rs76428106-C) in FLT3 increases seropositive RA risk (OR=1.35, p=6.6x10(-11)). Independent missense variants in TYK2 (rs34536443-C, rs12720356-C, rs35018800-A, latter two novel) associate with decreased risk of seropositive RA (ORs=0.63-0.87, p=10(-9)-10(-27)) and decreased plasma levels of interferon-alpha/beta receptor 1 that signals through TYK2/JAK1/STAT4. Conclusion Sequence variants pointing to causal genes in the JAK/STAT pathway have largest effect on seropositive RA, while associations with seronegative RA remain scarce.
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- Kuendig, H, et al.
(författare)
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Beyond drinking: differential effects of demographic and socioeconomic factors on alcohol-related adverse consequences across European countries
- 2008
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Ingår i: European addiction research. - : S. Karger AG. - 1421-9891 .- 1022-6877. ; 14:3, s. 150-160
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Tidskriftsartikel (refereegranskat)abstract
- <i>Background/Aims:</i> Evidence underlines the importance of drinking patterns and individual characteristics in experiencing adverse alcohol-related consequences; however, little research has been conducted to explore who does and who does not experience consequences with similar drinking patterns. Using data from seven European countries, this study assesses the association between demographic and socioeconomic characteristics and six adverse consequences. <i>Methods:</i> Conditional logistic regression models were estimated, cases (experiencing a consequence) being matched to controls (not experiencing the consequence) by drinking patterns. <i>Results:</i> In general, protective effects with increasing age and being in a partnership were consistent. Gender effects were mixed, but mainly protective for women. Educational achievement and economic status showed consistent effects across countries, but different directions of effect across consequences. Consequences mostly associated with individual drinking pattern <i>(injury, blackout</i>, and <i>loss of control over drinking)</i> exhibited similar patterns of associations, but varying ones arose for consequences additionally influenced by societal reaction to drinking <i>(guilt</i>, <i>role failure</i>, and <i>pressure to cut down drinking)</i>. <i>Conclusion:</i> Differences in strengths and directions of effects across consequences pointed to the possibility that the reporting of adverse consequences is not only influenced by alcohol consumption, but also by attributional processes related to demographic and socioeconomic statuses.
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- Lissner, Lauren, 1956, et al.
(författare)
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Television habits in relation to overweight, diet and taste preferences in European children: the IDEFICS study
- 2012
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Ingår i: European Journal of Epidemiology. - : Springer Science and Business Media LLC. - 0393-2990 .- 1573-7284. ; 27:9, s. 705-715
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Tidskriftsartikel (refereegranskat)abstract
- Early television exposure has been associated with various health outcomes including childhood obesity. This paper describes associations between patterns of television viewing, on one hand, and diet, taste preference and weight status, on the other, in European preschoolers and schoolchildren. The IDEFICS baseline survey was conducted at examination centers in Italy, Estonia, Cyprus, Belgium, Sweden, Germany, Hungary, and Spain. 15,144 children aged 2-9 completed the basic protocol, including anthropometry and parental questionnaires on their diets and television habits. A subsample of 1,696 schoolchildren underwent further sensory testing for fat and sweet taste preferences. Three dichotomous indicators described: children's habitual television exposure time; television viewing during meals; and having televisions in their bedrooms. Based on these variables we investigated television habits in relation to overweight (IOTF) and usual consumption of foods high in fat and sugar. A possible role of taste preference in the latter association was tested in the sensory subgroup. All television indicators were significantly associated with increased risk of overweight, with odds ratios ranging from 1.21 to 1.30, in fully adjusted models. Children's propensities to consume high-fat and high-sugar foods were positively and, in most analyses, monotonically associated with high-risk television behaviors. The associations between television and diet propensities were not explained by preference for added fat or sugar in test foods. To summarize, in addition to being more overweight, children with high-risk television behaviors may, independent of objectively measured taste preferences for fat and sugar, passively overconsume higher-fat and particularly higher-sugar diets.
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