| 1. |
|
|
| 2. |
|
|
| 3. |
|
|
| 4. |
- Tammiste, A, et al.
(författare)
-
Whole-exome sequencing identifies a polymorphism in the BMP5 gene associated with SSRI treatment response in major depression
- 2013
-
Ingår i: Journal of psychopharmacology (Oxford, England). - : SAGE Publications. - 1461-7285 .- 0269-8811. ; 27:10, s. 915-920
-
Tidskriftsartikel (refereegranskat)abstract
- Although antidepressants are widely used in the pharmacotherapy of major depressive disorder (MDD), their efficacy is still insufficient as approximately one-third of the patients do not fully recover even after several treatment trials. Inter-individual genetic differences are thought to contribute to the variability in antidepressant response; however, current findings from pharmacogenetic studies are uncertain or not clearly replicated. Here we report the first application of full exome sequencing for the analysis of pharmacogenomics on antidepressant treatment. After 12 weeks of treatment with the selective serotonin re-uptake inhibitor escitalopram, we selected five clear responders and five clear non-responders for exome sequencing. By comparing the allele counts of previously known single nucleotide polymorphisms and novel polymorphisms we selected 38 markers for further genotyping in two independent patient samples treated with escitalopram ( n=116 and n=394). The A allele, carried by approximately 30% of the patients with MDD, of rs41271330 in the bone morphogenetic protein (BMP5) gene showed strong association with worse treatment response in both sample sets ( p=0.001), indicating that this is an promising pharmacogenetic marker for prediction of antidepressant therapeutic outcome.
|
|
| 5. |
- Berndt, Sonja I., et al.
(författare)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Tidskriftsartikel (refereegranskat)abstract
- Approaches exploiting trait distribution extremes may be used to identify loci associated with common traits, but it is unknown whether these loci are generalizable to the broader population. In a genome-wide search for loci associated with the upper versus the lower 5th percentiles of body mass index, height and waist-to-hip ratio, as well as clinical classes of obesity, including up to 263,407 individuals of European ancestry, we identified 4 new loci (IGFBP4, H6PD, RSRC1 and PPP2R2A) influencing height detected in the distribution tails and 7 new loci (HNF4G, RPTOR, GNAT2, MRPS33P4, ADCY9, HS6ST3 and ZZZ3) for clinical classes of obesity. Further, we find a large overlap in genetic structure and the distribution of variants between traits based on extremes and the general population and little etiological heterogeneity between obesity subgroups.
|
|
| 6. |
|
|
| 7. |
- Nisula, Sara, et al.
(författare)
-
Incidence, risk factors and 90-day mortality of patients with acute kidney injury in Finnish intensive care units : the FINNAKI study
- 2013
-
Ingår i: Intensive Care Medicine. - : Springer Science and Business Media LLC. - 0342-4642 .- 1432-1238. ; 39:3, s. 420-428
-
Tidskriftsartikel (refereegranskat)abstract
- PURPOSEWe aimed to determine the incidence, risk factors and outcome of acute kidney injury (AKI) in Finnish ICUs.METHODSThis prospective, observational, multi-centre study comprised adult emergency admissions and elective patients whose stay exceeded 24 h during a 5-month period in 17 Finnish ICUs. We defined AKI first by the Acute Kidney Injury Network (AKIN) criteria supplemented with a baseline creatinine and second with the Kidney Disease: Improving Global Outcomes (KDIGO) criteria. We screened the patients' AKI status and risk factors for up to 5 days.RESULTSWe included 2,901 patients. The incidence (95 % confidence interval) of AKI was 39.3 % (37.5-41.1 %). The incidence was 17.2 % (15.8-18.6 %) for stage 1, 8.0 % (7.0-9.0 %) for stage 2 and 14.1 % (12.8-15.4 %) for stage 3 AKI. Of the 2,901 patients 296 [10.2 % (9.1-11.3 %)] received renal replacement therapy. We received an identical classification with the new KDIGO criteria. The population-based incidence (95 % CI) of ICU-treated AKI was 746 (717-774) per million population per year (reference population: 3,671,143, i.e. 85 % of the Finnish adult population). In logistic regression, pre-ICU hypovolaemia, diuretics, colloids and chronic kidney disease were independent risk factors for AKI. Hospital mortality (95 % CI) for AKI patients was 25.6 % (23.0-28.2 %) and the 90-day mortality for AKI patients was 33.7 % (30.9-36.5 %). All AKIN stages were independently associated with 90-day mortality.CONCLUSIONSThe incidence of AKI in the critically ill in Finland was comparable to previous large multi-centre ICU studies. Hospital mortality (26 %) in AKI patients appeared comparable to or lower than in other studies.
|
|
| 8. |
- Parsa, Afshin, et al.
(författare)
-
Common Variants in Mendelian Kidney Disease Genes and Their Association with Renal Function
- 2013
-
Ingår i: Journal of the American Society of Nephrology. - 1046-6673 .- 1533-3450. ; 24:12, s. 2105-2117
-
Tidskriftsartikel (refereegranskat)abstract
- Many common genetic variants identified by genome-wide association studies for complex traits map to genes previously linked to rare inherited Mendelian disorders. A systematic analysis of common single-nucleotide polymorphisms (SNPs) in genes responsible for Mendelian diseases with kidney phenotypes has not been performed. We thus developed a comprehensive database of genes for Mendelian kidney conditions and evaluated the association between common genetic variants within these genes and kidney function in the general population. Using the Online Mendelian Inheritance in Man database, we identified 731 unique disease entries related to specific renal search terms and confirmed a kidney phenotype in 218 of these entries, corresponding to mutations in 258 genes. We interrogated common SNPs (minor allele frequency >5%) within these genes for association with the estimated GFR in 74,354 European-ancestry participants from the CKDGen Consortium. However, the top four candidate SNPs (rs6433115 at LRP2, rs1050700 at TSC1, rs249942 at PALB2, and rs9827843 at ROBO2) did not achieve significance in a stage 2 meta-analysis performed in 56,246 additional independent individuals, indicating that these common SNPs are not associated with estimated GFR. The effect of less common or rare variants in these genes on kidney function in the general population and disease-specific cohorts requires further research.
|
|
