We performed a genome-wide association study (GWAS) in 1,713 Caucasian patients with Parkinson’s disease (PD) and 3,978 controls. After replication in 3,361 cases and 4,573 controls, two strong association signals were observed: in the α-synuclein gene(SNCA) (rs2736990, OR=1.23, p=2.24×10−16) and at the MAPT locus (rs393152, OR=0.77, p=1.95×10−16). We exchanged data with colleagues performing a GWAS in Asian PD cases. Association at SNCA was replicated in the Asian GWAS1, confirming this as a major risk locus across populations. We were able to replicate the effect of a novel locus detected in the Asian cohort (PARK16, rs823128, OR=0.66, p=7.29×10−8) and provide evidence supporting the role of common variability around LRRK2 in modulating risk for PD (rs1491923, OR=1.14, p=1.55×10−5). These data demonstrate an unequivocal role for common genetic variability in the etiology of typical PD and suggest population specific genetic heterogeneity in this disease.

Excess body weight during midlife, including overweight, is associated with an increased risk of death.

This paper describes the Observing Protein and Energy Nutrition (OPEN) Study, conducted from September 1999 to March 2000. The purpose of the study was to assess dietary measurement error using two self-reported dietary instruments-the food frequency questionnaire (FFQ) and the 24-hour dietary recall (24HR)-and unbiased biomarkers of energy and protein intakes: doubly labeled water and urinary nitrogen. Participants were 484 men and women aged 40-69 years from Montgomery County, Maryland. Nine percent of men and 7% of women were defined as underreporters of both energy and protein intake on 24HRs; for FFQs, the comparable values were 35% for men and 23% for women. On average, men underreported energy intake compared with total energy expenditure by 12-14% on 24HRs and 31-36% on FFQs and underreported protein intake compared with a protein biomarker by 11-12% on 24HRs and 30-34% on FFQs. Women underreported energy intake on 24HRs by 16-20% and on FFQs by 34-38% and underreported protein intake by 11-15% on 24HRs and 27-32% on FFQs. There was little underreporting of the percentage of energy from protein for men or women. These findings have important implications for nutritional epidemiology and dietary surveillance.

The American Cancer Society (ACS) publishes Nutrition and Physical ActivityGuidelines to serve as a foundation for its communication, policy, and community strategies and ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and as such, they represent the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines include recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or interferes with healthy behaviors. Community efforts are essential to create a social environment that promotes healthy food choices and physical activity. Therefore, this committee presents one key recommendation for community action to accompany the four recommendations for individual choices to reduce cancer risk. This recommendation for community action recognizes that a supportive social environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from

Multiple-day food records or 24-hour dietary recalls (24HRs) are commonly used as "reference" instruments to calibrate food frequency questionnaires (FFQs) and to adjust findings from nutritional epidemiologic studies for measurement error. Correct adjustment requires that the errors in the adopted reference instrument be independent of those in the FFQ and of true intake. The authors report data from the Observing Protein and Energy Nutrition (OPEN) Study, conducted from September 1999 to March 2000, in which valid reference biomarkers for energy (doubly labeled water) and protein (urinary nitrogen), together with a FFQ and 24HR, were observed in 484 healthy volunteers from Montgomery County, Maryland. Accounting for the reference biomarkers, the data suggest that the FFQ leads to severe attenuation in estimated disease relative risks for absolute protein or energy intake (a true relative risk of 2 would appear as 1.1 or smaller). For protein adjusted for energy intake by using either nutrient density or nutrient residuals, the attenuation is less severe (a relative risk of 2 would appear as approximately 1.3), lending weight to the use of energy adjustment. Using the 24HR as a reference instrument can seriously underestimate true attenuation (up to 60% for energy-adjusted protein). Results suggest that the interpretation of findings from FFQ-based epidemiologic studies of diet-disease associations needs to be reevaluated.

We discuss the implementation of a criterion due to Prentice for the statistical validation of intermediate endpoints for chronic disease. The criterion involves examining in a cohort or intervention study whether an exposure or intervention effect, adjusted for the intermediate endpoint, is reduced to zero. For example, to examine whether serum cholesterol level is an intermediate endpoint for coronary heart disease (CHD), we may investigate the effect of the cholesterol lowering drug cholestyramine on CHD incidence adjusted for serum cholesterol levels. We show that use of this criterion will usually demand some form of model selection. When the unadjusted exposure or treatment effect is less than four times its standard error, the analysis can usually lead only to a weak form of validation, a conclusion that the data are not inconsistent with the validation criterion. More significant unadjusted exposure effects offer the potential for stronger types of validation statement such as 'the intermediate endpoint explains at least 50 per cent (or 75 per cent) of the exposure effect'.

Background & Aims Limited data exist regarding the actual risk of developing advanced adenomas and cancer following polypectomy or the factors that determine risk. Methods We pooled individual data from 8 prospective studies comprising 9167 men and women aged 22 to 80 with previously-resected colorectal adenomas to quantify their risk of developing subsequent advanced adenoma or cancer as well as identify factors associated with development of advanced colorectal neoplasms during surveillance. Results During a median follow-up of 47.2 months, advanced colorectal neoplasia was diagnosed in 1082 (11.8%) of the patients, 58 of whom (0.6%) had invasive cancer. Risk of a metachronous advanced adenoma was higher among patients with 5 or more baseline adenomas (24.1%; SE=2.2) and those with an adenoma 20 mm in size or greater (19.3%; SE=1.5). Risk factor patterns were similar for advanced adenomas and invasive cancer. In multivariate analyses, older age (P <0.0001 for trend) and male sex (odds ratio [OR], 1.40; 95% confidence interval [CI] 1.19–1.65) were significantly associated with increased risk of metachronous advanced neoplasia, as were the number and size of prior adenomas (P <0.0001 for trend), the presence of villous features (OR, 1.28; 95% CI 1.07–1.52), and proximal location (OR, 1.68; 95% CI 1.43–1.98). High-grade dysplasia was not independently associated with metachronous advanced neoplasia after adjustment for other adenoma characteristics. Conclusions Occurrence of advanced colorectal neoplasia is common following polypectomy. Factors that are most strongly associated with risk of advanced neoplasia are patient age and the number and size of prior adenomas.

Adopting a diet that is low in fat and high in fiber, fruits, and vegetables does not influence the risk of recurrence of colorectal adenomas.