Genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease.

INTRODUCTION: Genetic factors and environmental exposures, including pesticides, contribute to the risk of Parkinson's disease (PD). There have been few studies of gene and pesticide exposure interactions in PD, and all of the prior studies used a candidate gene approach. METHODS: We performed the first genome-wide gene-environment interaction analysis of pesticide exposure and risk of Parkinson's disease. Analyses were performed using data on >700,000 single nucleotide polymorphisms (SNPs) in 364 discordant sibling pairs. In addition to testing for SNP-pesticide interaction effects, we also performed exploratory analyses of gene-pesticide interactions at the gene level. RESULTS: None of the gene-environment interaction results were significant after genome-wide correction for multiple testing (α = 1.5E-07 for SNP-level tests; α = 2.1E-06 for gene-level tests). Top results in the SNP-level tests provided suggestive evidence (P < 5.0E-06) that the effect of pesticide exposure on PD risk may be modified by SNPs in the ERCC6L2 gene (P = 2.4E-06), which was also supported by suggestive evidence in the gene-level analysis (P = 4.7E-05). None of the candidate genes assessed in prior studies of gene-pesticide interactions reached statistical support in this genome-wide screen. CONCLUSION: Although no significant interactions were identified, several of the genes with suggestive evidence of gene-environment interaction effects have biological plausibility for PD risk. Further investigation of the role of those genes in PD risk, particularly in the context of pesticide exposure, in large and carefully recruited samples is warranted.

Endoscopic overestimation of colorectal polyp size.

BACKGROUND AND AIMS: Polyp size ≥ 1 cm triggers more frequent colonoscopic surveillance, yet size is typically based on subjective endoscopic estimates. We sought to compare contemporary assessments of polyp size by endoscopic estimation and pathology measurement. METHODS: Colonoscopy and pathology reports were reviewed from the 2012 medical records at a large institution. Only polyps resected in toto with both endoscopic estimates and pathology measurements were included. Pathology measurements were considered the criterion standard. Factors affecting endoscopic miscall rates were assessed by multivariate analyses. RESULTS: From 6067 polyps resected, both endoscopic and pathology sizes were available on 1528. Distribution of polyp size appraised by endoscopy but not by pathology revealed modal clustering, particularly around 1 cm. Among 99 polyps endoscopically called 1 cm, 72% were <1 cm on pathology. Of all 222 polyps estimated as ≥ 1 cm on endoscopy, 46% were <1 cm on pathology; of 1306 polyps estimated as <1 cm, 3.9% were ≥ 1 cm on pathology. By histology, 39% of adenomatous, 59% of sessile serrated, and 73% of hyperplastic polyps were overcalled; P = .008. By configuration, 34% of pedunculated, 49% of sessile, and 61% of flat polyps were overcalled; P = .014. Endoscopic overestimation was more common in women (54%) than in men (40%) (P = .03) and with proximal (56%) than distal (40%) sites; P = .02. Miscall rates were unaffected by endoscopist covariates. CONCLUSIONS: Substantial discordance exists between endoscopic and pathology-based assessments of polyp size. Almost half of polyps called advanced on endoscopic estimates of size ≥ 1 cm fell below this threshold on actual pathology measurements.

The Mayo Clinic Biobank: a building block for individualized medicine.

OBJECTIVE: To report the design and implementation of the first 3 years of enrollment of the Mayo Clinic Biobank. PATIENTS AND METHODS: Preparations for this biobank began with a 4-day Deliberative Community Engagement with local residents to obtain community input into the design and governance of the biobank. Recruitment, which began in April 2009, is ongoing, with a target goal of 50,000. Any Mayo Clinic patient who is 18 years or older, able to consent, and a US resident is eligible to participate. Each participant completes a health history questionnaire, provides a blood sample, and allows access to existing tissue specimens and all data from their Mayo Clinic electronic medical record. A community advisory board provides ongoing advice and guidance on complex decisions. RESULTS: After 3 years of recruitment, 21,736 individuals have enrolled. Fifty-eight percent (12,498) of participants are female and 95% (20,541) of European ancestry. Median participant age is 62 years. Seventy-four percent (16,171) live in Minnesota, with 42% (9157) from Olmsted County, where the Mayo Clinic in Rochester, Minnesota, is located. The 5 most commonly self-reported conditions are hyperlipidemia (8979, 41%), hypertension (8174, 38%), osteoarthritis (6448, 30%), any cancer (6224, 29%), and gastroesophageal reflux disease (5669, 26%). Among patients with self-reported cancer, the 5 most common types are nonmelanoma skin cancer (2950, 14%), prostate cancer (1107, 12% in men), breast cancer (941, 4%), melanoma (692, 3%), and cervical cancer (240, 2% in women). Fifty-six percent (12,115) of participants have at least 15 years of electronic medical record history. To date, more than 60 projects and more than 69,000 samples have been approved for use. CONCLUSION: The Mayo Clinic Biobank has quickly been established as a valuable resource for researchers.

Hospitalizations and emergency department use in Mayo Clinic Biobank participants within the employee and community health medical home.

OBJECTIVE: To evaluate the participants in the Mayo Clinic Biobank for their representativeness to the entire Employee and Community Health program (ECH) primary care population with regard to hospital utilization. PATIENTS AND METHODS: Participants enrolled in the Mayo Clinic Biobank from April 1, 2009, to December 31, 2010, were linked to the ECH population. These individuals were categorized into risk tiers (0-4) on the basis of the number of health conditions present as of December 31, 2010. Outcomes were ascertained through December 31, 2011. Hazard ratios (HRs) and 95% CIs for risk of hospitalization, emergency department (ED) visits, and for risk of hospitalization and emergency department (ED) visits were estimated. RESULTS: The 8927 Biobank participants were part of ECH (N=84,872). Compared with the entire ECH population, the Biobank-ECH participants were more likely to be female (64.3% vs 54.6%), older (median age, 58 years vs 47 years), and categorized to tier 0 (6.4% vs 24.0%). There were strong positive associations between tier (tier 4 vs combined tiers 0 and 1) and risk of hospitalization (HR, 5.8; 95% CI, 4.6-7.5) and ED visits (HR, 5.4; 95% CI, 4.2-6.8) among Biobank-ECH participants. Similar associations for risk of hospitalization (HR, 8.5; 95% CI, 7.8-9.3) and ED visits (HR, 6.9; 95% CI, 6.4-7.5) were observed for the entire ECH population. CONCLUSION: Although the Biobank-ECH participants were older and had more chronic conditions compared with the overall ECH population, the associations of risk tier with utilization outcomes were similar, supporting the use of the Biobank participants to assess biomarkers for health care outcomes in the primary care setting.

Compliance with RSV prophylaxis: Global physicians' perspectives.

Respiratory syncytial virus (RSV) is a significant cause of morbidity in high-risk infants. Palivizumab is proven to prevent serious RSV disease, but compliance with prophylaxis (monthly doses during the RSV season) is essential to ensure protection. We invited 453 pediatricians to participate in a survey to identify their perspectives of barriers to compliance and interventions to improve compliance with palivizumab prophylaxis schedules. One hundred physicians from five continents completed the survey, identifying caregiver inconvenience, distance to clinic, cost of prophylaxis, and lack of understanding of the severity of RSV as the most common reasons for noncompliance. They recommended provision of educational materials about RSV, reminders from hospital or clinic, and administration of prophylaxis at home to increase compliance. Globally, physicians recognize several obstacles to prophylaxis compliance. This survey suggests that focused proactive interventions such as empowering caregivers with educational materials and reducing caregiver inconvenience may be instrumental to increase compliance.