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- Berndt, Sonja I., et al.
(författare)
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Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
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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.
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- Ganna, Andrea, et al.
(författare)
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Large-scale Metabolomic Profiling Identifies Novel Biomarkers for Incident Coronary Heart Disease
- 2014
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Ingår i: PLOS Genetics. - : Public Library of Science (PLoS). - 1553-7390 .- 1553-7404. ; 10:12, s. e1004801-
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Tidskriftsartikel (refereegranskat)abstract
- Analyses of circulating metabolites in large prospective epidemiological studies could lead to improved prediction and better biological understanding of coronary heart disease (CHD). We performed a mass spectrometry-based non-targeted metabolomics study for association with incident CHD events in 1,028 individuals (131 events; 10 y. median follow-up) with validation in 1,670 individuals (282 events; 3.9 y. median follow-up). Four metabolites were replicated and independent of main cardiovascular risk factors [lysophosphatidylcholine 18∶1 (hazard ratio [HR] per standard deviation [SD] increment = 0.77, P-value<0.001), lysophosphatidylcholine 18∶2 (HR = 0.81, P-value<0.001), monoglyceride 18∶2 (MG 18∶2; HR = 1.18, P-value = 0.011) and sphingomyelin 28∶1 (HR = 0.85, P-value = 0.015)]. Together they contributed to moderate improvements in discrimination and re-classification in addition to traditional risk factors (C-statistic: 0.76 vs. 0.75; NRI: 9.2%). MG 18∶2 was associated with CHD independently of triglycerides. Lysophosphatidylcholines were negatively associated with body mass index, C-reactive protein and with less evidence of subclinical cardiovascular disease in additional 970 participants; a reverse pattern was observed for MG 18∶2. MG 18∶2 showed an enrichment (P-value = 0.002) of significant associations with CHD-associated SNPs (P-value = 1.2×10-7 for association with rs964184 in the ZNF259/APOA5 region) and a weak, but positive causal effect (odds ratio = 1.05 per SD increment in MG 18∶2, P-value = 0.05) on CHD, as suggested by Mendelian randomization analysis. In conclusion, we identified four lipid-related metabolites with evidence for clinical utility, as well as a causal role in CHD development.
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- Språngberg, A, et al.
(författare)
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SBU. Godartad prostataförstoring med avflödeshinder. En systematisk litteraturöversikt : Godartad prostataförstoring med avflödeshinder
- 2011
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Rapport (övrigt vetenskapligt/konstnärligt)abstract
- Slutsatser Godartad prostataförstoring (benign prostatahyperplasi, BPH) är ett vanligt tillstånd som med stigande ålder drabbar i princip alla män. En del av dessa män får urineringsproblem och cirka 4 500 opereras varje år för en förstorad prostata. Många med lindrigare besvär behandlas med läkemedel eller behöver ingen behandling alls. Avflödeshinder kan obehandlat ge allvarlig urinretention som skadar njurarna, och en urinstämma kan vara livshotande. För att avgränsa den grupp av män där problemen med urineringen beror på en förstorad prostata används ett tiotal olika diagnostiska metoder. När det gäller behandling finns det flera olika kirurgiska metoder, varav några är väl etablerade och andra av mer experimentell karaktär. Under 1990-talet har också flera läkemedel introducerats. SBU har därför bedömt att det funnits ett behov av att göra en systematisk genomgång av den vetenskapliga grunden för dessa olika metoder. Nedan följer de viktigaste slutsatserna av arbetet.
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- Vasan, S K, et al.
(författare)
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A common variant in the FTO locus is associated with waist-hip ratio in Indian adolescents
- 2013
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Ingår i: Pediatric obesity. - : Wiley. - 2047-6310 .- 2047-6302. ; 8:3, s. e45-e49
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Common variants in the FTO locus, and near MC4R locus, have been shown to have a robust association with obesity in children and adults among various ethnic groups. Associations with obesity traits among Indian adolescents have not been determined.OBJECTIVE: To study the association of rs9939609 (FTO) and rs17782313 (MC4R) to obesity related anthropometric traits in Indian adolescents.METHODS: Subjects for the current study were recruited from a cross-sectional cohort of 1,230 adolescents (age mean ± SD: 17.1 ± 1.9 years) from South India.RESULTS: The variant at the FTO locus was found to be associated with waist-hip ratio (WHR) but not with overall obesity in this population. No significant association was observed for obesity-traits and Mc4R variant rs17782313.CONCLUSION: The common variant of FTO (rs9939609) is associated with body fat distribution during early growth in Indian adolescents and may predispose to obesity and metabolic consequences in adulthood.
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- Vasan, Senthil K, et al.
(författare)
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Associations of variants in FTO and near MC4R with obesity traits in South Asian Indians
- 2012
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Ingår i: Obesity. - : Wiley. - 1930-7381 .- 1930-739X. ; 20:11, s. 2268-2277
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Tidskriftsartikel (refereegranskat)abstract
- Recent genome-wide association studies show that loci in FTO and melanocortin 4 receptor (MC4R) associate with obesity-related traits. Outside Western populations the associations between these variants have not always been consistent and in Indians it has been suggested that FTO relates to diabetes without an obvious intermediary obesity phenotype. We investigated the association between genetic variants in FTO (rs9939609) and near MC4R (rs17782313) with obesity- and type 2 diabetes (T2DM)-related traits in a longitudinal birth cohort of 2,151 healthy individuals from the Vellore birth cohort in South India. The FTO locus displayed significant associations with several conventional obesity-related anthropometric traits. The per allele increase is about 1% for BMI, waist circumference (WC), hip circumference (HC), and waist-hip ratio. Consistent associations were observed for adipose tissue-specific measurements such as skinfold thickness reinforcing the association with obesity-related traits. Obesity associations for the MC4R locus were weak or nonsignificant but a signal for height (P < 0.001) was observed. The effect on obesity-related traits for FTO was seen in adulthood, but not at younger ages. The loci also showed nominal associations with increased blood glucose but these associations were lost on BMI adjustment. The effect of FTO on obesity-related traits was driven by an urban environmental influence. We conclude that rs9939609 variant in the FTO locus is associated with measures of adiposity and metabolic consequences in South Indians with an enhanced effect associated with urban living. The detection of these associations in Indians is challenging because conventional anthropometric obesity measures work poorly in the Indian "thin-fat" phenotype.
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