| 1. |
- Aad, G., et al.
(författare)
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- 2015
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Ingår i: Journal of High Energy Physics. - 1029-8479 .- 1126-6708. ; :3
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Tidskriftsartikel (refereegranskat)
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| 2. |
- Thorgeirsson, T. E., et al.
(författare)
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A rare missense mutation in CHRNA4 associates with smoking behavior and its consequences
- 2016
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Ingår i: Molecular Psychiatry. - : Springer Science and Business Media LLC. - 1359-4184 .- 1476-5578. ; 21:5, s. 594-600
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Tidskriftsartikel (refereegranskat)abstract
- Using Icelandic whole-genome sequence data and an imputation approach we searched for rare sequence variants in CHRNA4 and tested them for association with nicotine dependence. We show that carriers of a rare missense variant (allele frequency = 0.24%) within CHRNA4, encoding an R336C substitution, have greater risk of nicotine addiction than non-carriers as assessed by the Fagerstrom Test for Nicotine Dependence (P = 1.2 x 10(-4)). The variant also confers risk of several serious smoking-related diseases previously shown to be associated with the D398N substitution in CHRNA5. We observed odds ratios (ORs) of 1.7-2.3 for lung cancer (LC; P = 4.0 x 10(-4)), chronic obstructive pulmonary disease (COPD; P = 9.3 x 10(-4)), peripheral artery disease (PAD; P = 0.090) and abdominal aortic aneurysms (AAAs; P = 0.12), and the variant associates strongly with the early-onset forms of LC (OR = 4.49, P = 2.2 x 10(-4)), COPD (OR = 3.22, P = 2.9 x 10(-4)), PAD (OR = 3.47, P = 9.2 x 10(-3)) and AAA (OR = 6.44, P = 6.3 x 10(-3)). Joint analysis of the four smoking-related diseases reveals significant association (P = 6.8 x 10(-5)), particularly for early-onset cases (P = 2.1 x 10(-7)). Our results are in agreement with functional studies showing that the human alpha 4 beta 2 isoform of the channel containing R336C has less sensitivity for its agonists than the wild-type form following nicotine incubation.
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| 3. |
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| 4. |
- Johannesdottir, Hera, et al.
(författare)
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Favourable long-term outcome after coronary artery bypass grafting in a nationwide cohort
- 2017
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Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 51:6, s. 327-333
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Tidskriftsartikel (refereegranskat)abstract
- Objectives. In a nationwide cohort, we analyzed long-term outcome following coronary artery bypass grafting, using the combined strategy of left internal mammary artery to the left anterior descending artery and saphenous vein as secondary graft to other coronary targets. Methods. 1,507 consecutive patients that underwent myocardial revascularization during 2001-2012 in Iceland. Mean follow-up was 6.8 years. Major adverse cardiac and cerebrovascular events were depicted using the Kaplan-Meier method. Cox-regression was used to define risk factors. Relative survival was estimated by comparing overall survival to the survival of Icelanders of the same age and gender. Results. Mean age was 66 years, 83% were males, mean EuroSCOREst was 4.5, and 23% of the procedures were performed off-pump. At 5 years, 19.7% had suffered a major adverse cardiac or cerebrovascular event, 4.5% a stroke, 2.2% myocardial infarction, and 6.2% needed repeat revascularization. Overall 5-year survival was 89.9%, with a relative survival of 0.990. Independent predictors of major adverse cardiac and cerebrovascular events were left ventricular ejection fraction 30%, a previous history of percutaneous coronary intervention, chronic obstructive lung disease, chronic kidney disease, diabetes, and old age. The same variables and an earlier year of operation were predictors of long-term mortality. Conclusions. The long-term outcome following myocardial revascularization, using the left internal mammary artery and the great saphenous vein as conduits, is favourable and improving. This is reflected by the 5-year survival of 89.9%, deviating minimally from the survival rate of the general Icelandic population, together with a freedom from major adverse cardiac and cerebrovascular events of 80.3%.
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| 7. |
- Potjer, Thomas P., et al.
(författare)
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CM-Score : A validated scoring system to predict CDKN2A germline mutations in melanoma families from Northern Europe
- 2018
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Ingår i: Journal of Medical Genetics. - : BMJ. - 0022-2593 .- 1468-6244. ; 55:10, s. 661-668
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Tidskriftsartikel (refereegranskat)abstract
- Background: Several factors have been reported that influence the probability of a germline CDKN2A mutation in a melanoma family. Our goal was to create a scoring system to estimate this probability, based on a set of clinical features present in the patient and his or her family. Methods: Five clinical features and their association with CDKN2A mutations were investigated in a training cohort of 1227 Dutch melanoma families (13.7% with CDKN2A mutation) using multivariate logistic regression. Predefined features included number of family members with melanoma and with multiple primary melanomas, median age at diagnosis and presence of pancreatic cancer or upper airway cancer in a family member. Based on these five features, a scoring system (CDKN2A Mutation(CM)-Score) was developed and subsequently validated in a combined Swedish and Dutch familial melanoma cohort (n=421 families; 9.0% with CDKN2A mutation). Results: All five features were significantly associated (p<0.05) with a CDKN2A mutation. At a CM-Score of 16 out of 49 possible points, the threshold of 10% mutation probability is approximated (9.9%; 95% CI 9.8 to 10.1). This probability further increased to >90% for families with ≥36 points. A CM-Score under 16 points was associated with a low mutation probability (≤4%). CM-Score performed well in both the training cohort (area under the curve (AUC) 0.89; 95% CI 0.86 to 0.92) and the external validation cohort (AUC 0.94; 95% CI 0.90 to 0.98). Conclusion: We developed a practical scoring system to predict CDKN2A mutation status among melanoma-prone families. We suggest that CDKN2A analysis should be recommended to families with a CM-Score of ≥16 points.
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| 8. |
- Styrkarsdottir, Unnur, et al.
(författare)
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Whole-genome sequencing identifies rare genotypes in COMP and CHADL associated with high risk of hip osteoarthritis
- 2017
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 49:5, s. 801-805
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Tidskriftsartikel (refereegranskat)abstract
- We performed a genome-wide association study of total hip replacements, based on variants identified through whole-genome sequencing, which included 4,657 Icelandic patients and 207,514 population controls. We discovered two rare signals that strongly associate with osteoarthritis total hip replacement: a missense variant, c.1141G>C (p.Asp369His), in the COMP gene (allelic frequency = 0.026%, P = 4.0 × 10-12, odds ratio (OR) = 16.7) and a frameshift mutation, rs532464664 (p.Val330Glyfs∗106), in the CHADL gene that associates through a recessive mode of inheritance (homozygote frequency = 0.15%, P = 4.5 × 10-18, OR = 7.71). On average, c.1141G>C heterozygotes and individuals homozygous for rs532464664 had their hip replacement operation 13.5 years and 4.9 years earlier than others (P = 0.0020 and P = 0.0026), respectively. We show that the full-length CHADL transcript is expressed in cartilage. Furthermore, the premature stop codon introduced by the CHADL frameshift mutation results in nonsense-mediated decay of the mutant transcripts.
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| 10. |
- Garoarsdottir, Helga Run, et al.
(författare)
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Árangur kransæðahjáveituaðgerða hjá konum á Íslandi
- 2018
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Ingår i: Laeknabladid. - : LAEKNAFELAG ISLANDS-ICELANDIC MEDICAL ASSOC. - 0023-7213 .- 1670-4959. ; 104:7-8, s. 335-340
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Tidskriftsartikel (refereegranskat)abstract
- InngangurMarkmið þessarar rannsóknar var að bera saman árangur kransæða-hjáveituaðgerða hjá konum og körlum á Íslandi með áherslu á snemm- og síðkomna fylgikvilla, 30 daga dánartíðni og langtímalifun.Efniviður og aðferðirAfturskyggn rannsókn á öllum sjúklingum sem gengust undir kransæðahjáveituaðgerð á Íslandi á árunum 2001-2013. Upplýsingar fengust úr sjúkraskrám og Dánarmeinaskrá Embættis landlæknis. Fylgikvillum var skipt í snemm- og síðkomna fylgikvilla og heildarlif-un reiknuð með aðferð Kaplan-Meier. Fjölþátta aðhvarfsgreining var notuð til að meta forspárþætti dauða innan 30 daga og Cox aðhvarfs-greining til að meta forspárþætti verri langtímalifunar. Meðaleftirfylgd var 6,8 ár. NiðurstöðurAf 1755 sjúklingum voru 318 konur (18%). Meðalaldur þeirra var fjórum árum hærri en karla (69 ár á móti 65 árum, p<0,001), þær höfðu oftar sögu um háþrýsting (72% á móti 64%, p=0,009) og EuroSCOREst þeirra var hærra (6,1 á móti 4,3, p<0,001). Hlutfall annarra áhættu-þátta eins og sykursýki var hins vegar sambærilegt, líkt og útbreiðsla kransæðasjúkdóms. Alls létust 12 konur (4%) og 30 karlar (2%) innan 30 daga frá aðgerð en munurinn var ekki marktækur (p=0,08). Tíðni snemmkominna fylgikvilla, bæði minniháttar (53% á móti 48% p=0,07) og alvarlegra (13% á móti 11%, p=0,2), var sambærileg. Fimm árum frá aðgerð var lifun kvenna 87% borin saman við 90% hjá körlum (p=0,09). Þá var tíðni síðkominna fylgikvilla sambærileg hjá konum og körlum 5 árum frá aðgerð (21% á móti 19%, p=0,3). Kvenkyn reyndist hvorki sjálfstæður forspárþáttur 30 daga dánartíðni (OR 0,99; 95%-ÖB: 0,97-1,01) né verri lifunar (HR 1,08; 95%-ÖB: 0,82-1,42).Ályktun Mun færri konur en karlar gangast undir kransæðahjáveituaðgerð á Íslandi og eru þær fjórum árum eldri þegar kemur að aðgerð. Árangur kransæðahjáveitu er góður hjá konum líkt og körlum, en 5 árum eftir aðgerð eru 87% kvenna á lífi.
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