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Sökning: WFRF:(Kiemeney L) > Khaw Kay Tee

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1.
  • Speliotes, Elizabeth K., et al. (författare)
  • Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
  • 2010
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
  • Tidskriftsartikel (refereegranskat)abstract
    • Obesity is globally prevalent and highly heritable, but its underlying genetic factors remain largely elusive. To identify genetic loci for obesity susceptibility, we examined associations between body mass index and ~2.8 million SNPs in up to 123,865 individuals with targeted follow up of 42 SNPs in up to 125,931 additional individuals. We confirmed 14 known obesity susceptibility loci and identified 18 new loci associated with body mass index (P < 5 × 10−8), one of which includes a copy number variant near GPRC5B. Some loci (at MC4R, POMC, SH2B1 and BDNF) map near key hypothalamic regulators of energy balance, and one of these loci is near GIPR, an incretin receptor. Furthermore, genes in other newly associated loci may provide new insights into human body weight regulation.
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2.
  • 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.
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3.
  • Yang, Jian, et al. (författare)
  • FTO genotype is associated with phenotypic variability of body mass index
  • 2012
  • Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
  • Tidskriftsartikel (refereegranskat)abstract
    • There is evidence across several species for genetic control of phenotypic variation of complex traits(1-4), such that the variance among phenotypes is genotype dependent. Understanding genetic control of variability is important in evolutionary biology, agricultural selection programmes and human medicine, yet for complex traits, no individual genetic variants associated with variance, as opposed to the mean, have been identified. Here we perform a meta-analysis of genome-wide association studies of phenotypic variation using similar to 170,000 samples on height and body mass index (BMI) in human populations. We report evidence that the single nucleotide polymorphism (SNP) rs7202116 at the FTO gene locus, which is known to be associated with obesity (as measured by mean BMI for each rs7202116 genotype)(5-7), is also associated with phenotypic variability. We show that the results are not due to scale effects or other artefacts, and find no other experiment-wise significant evidence for effects on variability, either at loci other than FTO for BMI or at any locus for height. The difference in variance for BMI among individuals with opposite homozygous genotypes at the FTO locus is approximately 7%, corresponding to a difference of similar to 0.5 kilograms in the standard deviation of weight. Our results indicate that genetic variants can be discovered that are associated with variability, and that between-person variability in obesity can partly be explained by the genotype at the FTO locus. The results are consistent with reported FTO by environment interactions for BMI8, possibly mediated by DNA methylation(9,10). Our BMI results for other SNPs and our height results for all SNPs suggest that most genetic variants, including those that influence mean height or mean BMI, are not associated with phenotypic variance, or that their effects on variability are too small to detect even with samples sizes greater than 100,000.
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4.
  • Purdue, Mark P, et al. (författare)
  • Genome-wide association study of renal cell carcinoma identifies two susceptibility loci on 2p21 and 11q13.3
  • 2011
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 43:1, s. 60-65
  • Tidskriftsartikel (refereegranskat)abstract
    • We conducted a two-stage genome-wide association study of renal cell carcinoma (RCC) in 3,772 affected individuals (cases) and 8,505 controls of European background from 11 studies and followed up 6 SNPs in 3 replication studies of 2,198 cases and 4,918 controls. Two loci on the regions of 2p21 and 11q13.3 were associated with RCC susceptibility below genome-wide significance. Two correlated variants (r² = 0.99 in controls), rs11894252 (P = 1.8 × 10⁻⁸) and rs7579899 (P = 2.3 × 10⁻⁹), map to EPAS1 on 2p21, which encodes hypoxia-inducible-factor-2 alpha, a transcription factor previously implicated in RCC. The second locus, rs7105934, at 11q13.3, contains no characterized genes (P = 7.8 × 10⁻¹⁴). In addition, we observed a promising association on 12q24.31 for rs4765623, which maps to SCARB1, the scavenger receptor class B, member 1 gene (P = 2.6 × 10⁻⁸). Our study reports previously unidentified genomic regions associated with RCC risk that may lead to new etiological insights.
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5.
  • Allen, Naomi E., et al. (författare)
  • Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
  • 2013
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:3, s. 635-644
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous studies have suggested that dietary factors may be important in the development of bladder cancer. We examined macronutrient intake in relation to risk of urothelial cell carcinoma among 469,339 men and women in the European Prospective Investigation into Cancer and Nutrition. Associations were examined using Cox regression, stratified by sex, age at recruitment and centre and further adjusted for smoking status and duration, body mass index and total energy intake. After an average of 11.3 years of follow-up, 1,416 new cases of urothelial cell carcinoma were identified. After allowing for measurement error, a 3% increase in the consumption of energy intake from animal protein was associated with a 15% higher risk (95% confidence interval [CI]: 330%; ptrend = 0.01) and a 2% increase in energy from plant protein intake was associated with a 23% lower risk (95% CI: 367%, ptrend = 0.006). Dietary intake of fat, carbohydrate, fibre or calcium was not associated with risk. These findings suggest that animal and/or plant protein may affect the risk of urothelial cell carcinoma, and examination of these associations in other studies is needed.
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6.
  • Büchner, Frederike L, et al. (författare)
  • Variety in fruit and vegetable consumption and the risk of lung cancer in the European prospective investigation into cancer and nutrition
  • 2010
  • Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:9, s. 2278-2286
  • Tidskriftsartikel (refereegranskat)abstract
    • BACKGROUND: We investigated whether a varied consumption of vegetables and fruits is associated with lower lung cancer risk in the European Prospective Investigation into Cancer and Nutrition study. METHODS: After a mean follow-up of 8.7 years, 1,613 of 452,187 participants with complete information were diagnosed with lung cancer. Diet diversity scores (DDS) were used to quantify the variety in fruit and vegetable consumption. Multivariable proportional hazards models were used to assess the associations between DDS and lung cancer risk. All models were adjusted for smoking behavior and the total consumption of fruit and vegetables. RESULTS: With increasing variety in vegetable subgroups, risk of lung cancer decreases [hazard ratios (HR), 0.77; 95% confidence interval (CI), 0.64-0.94 highest versus lowest quartile; P trend = 0.02]. This inverse association is restricted to current smokers (HR, 0.73; 95% CI, 0.57-0.93 highest versus lowest quartile; P trend = 0.03). In continuous analyses, in current smokers, lower risks were observed for squamous cell carcinomas with more variety in fruit and vegetable products combined (HR/two products, 0.88; 95% CI, 0.82-0.95), vegetable subgroups (HR/subgroup, 0.88; 95% CI, 0.79-0.97), vegetable products (HR/two products, 0.87; 95% CI, 0.79-0.96), and fruit products (HR/two products, 0.84; 95% CI, 0.72-0.97). CONCLUSION: Variety in vegetable consumption was inversely associated with lung cancer risk among current smokers. Risk of squamous cell carcinomas was reduced with increasing variety in fruit and/or vegetable consumption, which was mainly driven by the effect in current smokers. IMPACT: Independent from quantity of consumption, variety in fruit and vegetable consumption may decrease lung cancer risk.
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7.
  • Büchner, Frederike L, et al. (författare)
  • Variety in vegetable and fruit consumption and risk of bladder cancer in the European prospective investigation into cancer and nutrition
  • 2011
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:12, s. 2971-2979
  • Tidskriftsartikel (refereegranskat)abstract
    • Recent research does not show an association between fruit and vegetable consumption and bladder cancer risk. None of these studies investigated variety in fruit and vegetable consumption, which may capture different aspects of consumption. We investigated whether a varied consumption of vegetables and fruits is associated with bladder cancer risk in the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Detailed data on food consumption and complete follow-up for cancer incidence were available for 452,185 participants, who were recruited from ten European countries. After a mean follow-up of 8.7 years, 874 participants were diagnosed with bladder cancer. Diet diversity scores (DDSs) were used to quantify the variety in fruit and vegetable consumption. Multivariable Cox proportional hazard models were used to assess the effect of the DDSs on bladder cancer risk. There was no evidence of a statistically significant association between bladder cancer risk and any of the DDSs when these scores were considered as continuous covariates. However, the hazard ratio (HR) for the highest tertile of the DDS for combined fruit and vegetable consumption was marginally significant compared to the lowest (HR = 1.30, 95% confidence interval: 1.00-1.69, p-trend = 0.05). In EPIC, there is no clear association between a varied fruit and vegetable consumption and bladder cancer risk. This finding provides further evidence for the absence of any strong association between fruit and vegetable consumption as measured by a food frequency questionnaire and bladder cancer risk.
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8.
  • Buechner, Frederike L., et al. (författare)
  • Consumption of vegetables and fruit and the risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition
  • 2009
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:11, s. 2643-2651
  • Tidskriftsartikel (refereegranskat)abstract
    • Previous epidemiologic studies found inconsistent associations between vegetables and fruit consumption and the risk of bladder cancer. We therefore investigated the association between vegetable and fruit consumption and the risk of bladder cancer among participants of the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Data on food consumption and complete follow-up for cancer occurrence was available for a total of 478,533 participants, who were recruited in 10 European countries. Estimates of rate ratios were obtained by Cox proportional hazard models, stratified by age at recruitment, gender and study centre, and adjusted for total energy intake, smoking status, duration of smoking and lifetime intensity of smoking. A calibration study in a subsample was used to control for dietary measurement errors. After a mean follow-up of 8.7 years, 1015 participants were newly diagnosed with bladder cancer. Increments of 100 g/day in fruit and vegetable consumption combined did not affect bladder cancer risk (i.e., calibrated HR = 0.98; 95%CI: 0.95-1.01). Borderline statistically significant lower bladder cancer risks were found among fever smokers with increased consumption of fruit and vegetables combined (HR = 0.94 95%CI: 0.87-1.00 with increments of 100 g/day; calibrate HR = 0.92 95%CI 0.79-1.06) and increased consumption of apples and pears (hard fruit; calibrated HR = 0.90 95%CI: 0.82-0.98 with increments of 25 g/day). For none of the associations a statistically significant interaction with smoking status was found. Our findings do not support an effect of fruit and vegetable consumption, combined or separately, on bladder cancer risk. (c) 2009 UICC
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9.
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10.
  • Ros, Martine M., et al. (författare)
  • Fluid intake and the risk of urothelial cell carcinomas in the European Prospective Investigation into Cancer and Nutrition (EPIC)
  • 2011
  • Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 128:11, s. 2695-2708
  • Tidskriftsartikel (refereegranskat)abstract
    • Results from previous studies investigating the association between fluid intake and urothelial cell carcinomas (UCC) are inconsistent. We evaluated this association among 233,236 subjects in the European Prospective Investigation into Cancer and Nutrition (EPIC), who had adequate baseline information on water and total fluid intake. During a mean follow-up of 9.3 years, 513 first primary UCC occurred. At recruitment, habitual fluid intake was assessed by a food frequency questionnaire. Multivariable hazard ratios were estimated using Cox regression stratified by age, sex and center and adjusted for energy intake, smoking status, duration of smoking and lifetime intensity of smoking. When using the lowest tertile of intake as reference, total fluid intake was not associated with risk of all UCC (HR 1.12; 95% CI 0.86-1.45, p-trend = 0.42) or with risk of prognostically high-risk UCC (HR 1.28; 95% CI 0.85-1.93, p-trend = 0.27) or prognostically low-risk UCC (HR 0.93; 95% CI 0.65-1.33, p-trend = 0.74). No associations were observed between risk of UCC and intake of water, coffee, tea and herbal tea and milk and other dairy beverages. For prognostically low-risk UCC suggestions of an inverse association with alcoholic beverages and of a positive association with soft drinks were seen. Increased risks were found for all UCC and prognostically low-risk UCC with higher intake of fruit and vegetable juices. In conclusion, total usual fluid intake is not associated with UCC risk in EPIC. The relationships observed for some fluids may be due to chance, but further investigation of the role of all types of fluid is warranted.
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