| 1. |
- Berndt, Sonja I., et al.
(author)
-
Genome-wide meta-analysis identifies 11 new loci for anthropometric traits and provides insights into genetic architecture
- 2013
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:5, s. 501-U69
-
Journal article (peer-reviewed)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.
|
|
| 2. |
- Speliotes, Elizabeth K., et al.
(author)
-
Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:11, s. 937-948
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- Yang, Jian, et al.
(author)
-
FTO genotype is associated with phenotypic variability of body mass index
- 2012
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 490:7419, s. 267-272
-
Journal article (peer-reviewed)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.
|
|
| 4. |
|
|
| 5. |
- Buechner, Frederike L., et al.
(author)
-
Consumption of vegetables and fruit and the risk of bladder cancer in the European Prospective Investigation into Cancer and Nutrition
- 2009
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:11, s. 2643-2651
-
Journal article (peer-reviewed)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
|
|
| 6. |
- Crowe, Francesca L., et al.
(author)
-
Dietary fat intake and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition
- 2008
-
In: American Journal of Clinical Nutrition. - 1938-3207. ; 87:5, s. 1405-1413
-
Journal article (peer-reviewed)abstract
- Background: Findings from early observational studies have suggested that the intake of dietary fat might be a contributing factor in the etiology of prostate cancer. However, the results from more recent prospective studies do not support this hypothesis, and the possible association between different food sources of fat and prostate cancer risk also remains unclear. Objective: The objectives were to assess whether intakes of dietary fat, subtypes of fat, and fat from animal products were associated with prostate cancer risk. Design: This was a multicenter prospective study of 142 520 men in the European Prospective Investigation into Cancer and Nutrition (EPIC). Dietary fat intake was estimated with the use of country-specific validated food questionnaires. The association between dietary fat and risk of prostate cancer was assessed by using Cox regression, stratified by recruitment center and adjusted for height, weight, smoking, education, marital status, and energy intake. Results: After a median follow-up time of 8.7 y, prostate cancer was diagnosed in 2727 men. There was no significant association between dietary fat (total, saturated, monounsaturated, and polyunsaturated fat and the ratio of polyunsaturated to saturated fat) and risk of prostate cancer. The hazard ratio for prostate cancer for the highest versus the lowest quintile of total fat intake was 0.96 (95% CI: 0.84, 1.09; P for trend = 0.155). There were no significant associations between prostate cancer risk and fat from red meat, dairy products, and fish. Conclusion: The results from this large multicenter study suggest that there is no association between dietary fat and prostate cancer risk.
|
|
| 7. |
|
|
| 8. |
- Johansson, Mattias, et al.
(author)
-
Circulating concentrations of folate and vitamin B12 in relation to prostate cancer risk : results from the European prospective investigation into cancer and nutrition study
- 2008
-
In: Cancer Epidemiol Biomarkers Prev. - 1055-9965. ; 17:2, s. 279-285
-
Journal article (peer-reviewed)abstract
- Background: Determinants of one-carbon metabolism, such as folate and vitamin B12, have been implicated in cancer development. Previous studies have not provided conclusive evidence for the importance of circulating concentrations of folate and vitamin B12 in prostate cancer etiology. The aim of the present study was to investigate the relationship between prostate cancer risk and circulating concentrations of folate and vitamin B12 in a large prospective cohort. Methods: We analyzed circulating concentrations of folate and vitamin B12 in 869 cases and 1,174 controls, individually matched on center, age, and date of recruitment, nested within the European Prospective Investigation into Cancer and Nutrition cohort. Relative risks (RR) for prostate cancer were estimated using conditional logistic regression models. Results: Overall, no significant associations were observed for circulating concentrations of folate (Ptrend = 0.62) or vitamin B12 (Ptrend = 0.21) with prostate cancer risk. RRs for a doubling in folate and vitamin B12 concentrations were 1.03 [95% confidence interval (95% CI), 0.92-1.16] and 1.12 (95% CI, 0.94-1.35), respectively. In the subgroup of cases diagnosed with advanced stage prostate cancer, elevated concentrations of vitamin B12 were associated with increased risk (RR for a doubling in concentration, 1.69; 95% CI, 1.05-2.72, Ptrend = 0.03). No other subgroup analyses resulted in a statistically significant association. Conclusion: This study does not provide strong support for an association between prostate cancer risk and circulating concentrations of folate or vitamin B12. Elevated concentrations of vitamin B12 may be associated with an increased risk for advanced stage prostate cancer, but this association requires examination in other large prospective studies. (Cancer Epidemiol Biomarkers Prev 2007;17(2):279–85)
|
|
| 9. |
- Johnsen, Nina Fans, et al.
(author)
-
Physical activity and risk of prostate cancer in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort
- 2009
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 125:4, s. 902-908
-
Journal article (peer-reviewed)abstract
- The evidence concerning the possible association between physical activity and the risk of prostate cancer is inconsistent and additional data are needed. We examined the association between risk of prostate cancer and physical activity at work and in leisure time in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In our study, including 127,923 men aged 20-97 years from 8 European countries, 2,458 cases of prostate cancer were identified during 8.5 years of followup. Using the Cox proportional hazards model, we investigated the associations between prostate cancer incidence rate and occupational activity and leisure time activity in terms of participation in sports, cycling, walking and gardening; a metabolic equivalent (MET) score based on weekly time spent on the 4 activities; and a physical activity index. MET hours per week of leisure time activity, higher score in the physical activity index, participation in any of the 4 leisure time activities, and the number of leisure time activities in which the participants were active were not associated with prostate cancer incidence. However, higher level of occupational physical activity was associated with lower risk of advanced stage prostate cancer (p(trend) = 0.024). In conclusion, our data support the hypothesis of an inverse association between advanced prostate cancer risk and occupational physical activity, but we found no support for an association between prostate cancer risk and leisure time physical activity. (C) 2009 UICC
|
|
| 10. |
- Allen, Naomi E., et al.
(author)
-
Macronutrient intake and risk of urothelial cell carcinoma in the European prospective investigation into cancer and nutrition
- 2013
-
In: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 132:3, s. 635-644
-
Journal article (peer-reviewed)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.
|
|
