| 1. |
- Amundadottir, Laufey T., et al.
(författare)
-
A common variant associated with prostate cancer in European and African populations
- 2006
-
Ingår i: Nature Genetics. - DeCODE Genet, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Pathol, IS-101 Reykjavik, Iceland. Univ Iceland, Landspitali Hosp, Dept Urol, IS-101 Reykjavik, Iceland. Univ Michigan, Dept Human Genet, Ann Arbor, MI 48109 USA. Orebro Univ Hosp, Dept Urol & Clin Med, Orebro, Sweden. Karolinska Inst, Dept Med Epidemiol & Biostat, SE-17177 Stockholm, Sweden. Univ Michigan, Dept Urol, Ann Arbor, MI 48109 USA. Northwestern Univ, Feinberg Sch Med, Dept Urol, Chicago, IL 60611 USA. Washington Univ, Sch Med, Dept Psychiat, St Louis, MO 63110 USA. Univ Chicago, Dept Human Genet, Chicago, IL 60637 USA. Univ Michigan, Dept Internal Med, Ann Arbor, MI 48109 USA. : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 38:6, s. 652-658
-
Tidskriftsartikel (refereegranskat)abstract
- With the increasing incidence of prostate cancer, identifying common genetic variants that confer risk of the disease is important. Here we report such a variant on chromosome 8q24, a region initially identified through a study of Icelandic families. Allele -8 of the microsatellite DG8S737 was associated with prostate cancer in three case-control series of European ancestry from Iceland, Sweden and the US. The estimated odds ratio (OR) of the allele is 1.62 (P = 2.7 x 10(-11)). About 19% of affected men and 13% of the general population carry at least one copy, yielding a population attributable risk (PAR) of approximately 8%. The association was also replicated in an African American case-control group with a similar OR, in which 41% of affected individuals and 30% of the population are carriers. This leads to a greater estimated PAR (16%) that may contribute to higher incidence of prostate cancer in African American men than in men of European ancestry.
|
|
| 2. |
|
|
| 3. |
- Helgadottir, Anna, et al.
(författare)
-
Genome-wide analysis yields new loci associating with aortic valve stenosis
- 2018
-
Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1
-
Tidskriftsartikel (refereegranskat)abstract
- Aortic valve stenosis (AS) is the most common valvular heart disease, and valve replacement is the only definitive treatment. Here we report a large genome-wide association (GWA) study of 2,457 Icelandic AS cases and 349,342 controls with a follow-up in up to 4,850 cases and 451,731 controls of European ancestry. We identify two new AS loci, on chromosome 1p21 near PALMD (rs7543130; odds ratio (OR) = 1.20, P = 1.2 × 10-22) and on chromosome 2q22 in TEX41 (rs1830321; OR = 1.15, P = 1.8 × 10-13). Rs7543130 also associates with bicuspid aortic valve (BAV) (OR = 1.28, P = 6.6 × 10-10) and aortic root diameter (P = 1.30 × 10-8), and rs1830321 associates with BAV (OR = 1.12, P = 5.3 × 10-3) and coronary artery disease (OR = 1.05, P = 9.3 × 10-5). The results implicate both cardiac developmental abnormalities and atherosclerosis-like processes in the pathogenesis of AS. We show that several pathways are shared by CAD and AS. Causal analysis suggests that the shared risk factors of Lp(a) and non-high-density lipoprotein cholesterol contribute substantially to the frequent co-occurence of these diseases.
|
|
| 4. |
- Johannesdottir, Hera, et al.
(författare)
-
Favourable long-term outcome after coronary artery bypass grafting in a nationwide cohort
- 2017
-
Ingår i: Scandinavian Cardiovascular Journal. - : Informa UK Limited. - 1401-7431 .- 1651-2006. ; 51:6, s. 327-333
-
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%.
|
|
| 5. |
- Kiemeney, Lambertus A, et al.
(författare)
-
A sequence variant at 4p16.3 confers susceptibility to urinary bladder cancer.
- 2010
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 42:5, s. 415-9
-
Tidskriftsartikel (refereegranskat)abstract
- Previously, we reported germline DNA variants associated with risk of urinary bladder cancer (UBC) in Dutch and Icelandic subjects. Here we expanded the Icelandic sample set and tested the top 20 markers from the combined analysis in several European case-control sample sets, with a total of 4,739 cases and 45,549 controls. The T allele of rs798766 on 4p16.3 was found to associate with UBC (odds ratio = 1.24, P = 9.9 x 10(-12)). rs798766 is located in an intron of TACC3, 70 kb from FGFR3, which often harbors activating somatic mutations in low-grade, noninvasive UBC. Notably, rs798766[T] shows stronger association with low-grade and low-stage UBC than with more aggressive forms of the disease and is associated with higher risk of recurrence in low-grade stage Ta tumors. The frequency of rs798766[T] is higher in Ta tumors that carry an activating mutation in FGFR3 than in Ta tumors with wild-type FGFR3. Our results show a link between germline variants, somatic mutations of FGFR3 and risk of UBC.
|
|
| 6. |
|
|
| 7. |
- Rafnar, Thorunn, et al.
(författare)
-
European genome-wide association study identifies SLC14A1 as a new urinary bladder cancer susceptibility gene.
- 2011
-
Ingår i: Human molecular genetics. - : Oxford University Press (OUP). - 1460-2083 .- 0964-6906. ; 20:21, s. 4268-81
-
Tidskriftsartikel (refereegranskat)abstract
- Three genome-wide association studies in Europe and the USA have reported eight urinary bladder cancer (UBC) susceptibility loci. Using extended case and control series and 1000 Genomes imputations of 5 340 737 single-nucleotide polymorphisms (SNPs), we searched for additional loci in the European GWAS. The discovery sample set consisted of 1631 cases and 3822 controls from the Netherlands and 603 cases and 37 781 controls from Iceland. For follow-up, we used 3790 cases and 7507 controls from 13 sample sets of European and Iranian ancestry. Based on the discovery analysis, we followed up signals in the urea transporter (UT) gene SLC14A. The strongest signal at this locus was represented by a SNP in intron 3, rs17674580, that reached genome-wide significance in the overall analysis of the discovery and follow-up groups: odds ratio = 1.17, P = 7.6 × 10(-11). SLC14A1 codes for UTs that define the Kidd blood group and are crucial for the maintenance of a constant urea concentration gradient in the renal medulla and, through this, the kidney's ability to concentrate urine. It is speculated that rs17674580, or other sequence variants in LD with it, indirectly modifies UBC risk by affecting urine production. If confirmed, this would support the 'urogenous contact hypothesis' that urine production and voiding frequency modify the risk of UBC.
|
|
