title: A Neighborhood-Wide Association Study (NWAS): Example of prostate cancer aggressiveness.
abstract: OBJECTIVE
  Cancer results from complex interactions of multiple variables at the biologic, individual, and social levels. Compared to other levels, social effects that occur geospatially in neighborhoods are not as well-studied, and empiric methods to assess these effects are limited. We propose a novel Neighborhood-Wide Association Study(NWAS), analogous to genome-wide association studies(GWAS), that utilizes high-dimensional computing approaches from biology to comprehensively and empirically identify neighborhood factors associated with disease.
  
  
  METHODS
  Pennsylvania Cancer Registry data were linked to U.S. Census data. In a successively more stringent multiphase approach, we evaluated the association between neighborhood (n = 14,663 census variables) and prostate cancer aggressiveness(PCA) with n = 6,416 aggressive (Stage≥3/Gleason grade≥7 cases) vs. n = 70,670 non-aggressive (Stage<3/Gleason grade<7) cases in White men. Analyses accounted for age, year of diagnosis, spatial correlation, and multiple-testing. We used generalized estimating equations in Phase 1 and Bayesian mixed effects models in Phase 2 to calculate odds ratios(OR) and confidence/credible intervals(CI). In Phase 3, principal components analysis grouped correlated variables.
  
  
  RESULTS
  We identified 17 new neighborhood variables associated with PCA. These variables represented income, housing, employment, immigration, access to care, and social support. The top hits or most significant variables related to transportation (OR = 1.05;CI = 1.001-1.09) and poverty (OR = 1.07;CI = 1.01-1.12).
  
  
  CONCLUSIONS
  This study introduces the application of high-dimensional, computational methods to large-scale, publically-available geospatial data. Although NWAS requires further testing, it is hypothesis-generating and addresses gaps in geospatial analysis related to empiric assessment. Further, NWAS could have broad implications for many diseases and future precision medicine studies focused on multilevel risk factors of disease.
authors.affiliation: Fox Chase Cancer Center, Cancer Prevention and Control, Philadelphia, Pennsylvania, United States of America.
authors.forename: Shannon M
authors.initials: SM
authors.lastname: Lynch
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Nandita
authors.initials: N
authors.lastname: Mitra
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Ross
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Craig
authors.initials: C
authors.lastname: Newcomb
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Karl
authors.initials: K
authors.lastname: Dailey
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.
authors.forename: Tara
authors.initials: T
authors.lastname: Jackson
authors.affiliation: Thomas Jefferson University, Philadelphia, Pennsylvania, United States of America.
authors.forename: Charnita M
authors.initials: CM
authors.lastname: Zeigler-Johnson
authors.affiliation: Old Dominion University, Norfolk, Virginia, United States of America.
authors.forename: Harold
authors.initials: H
authors.lastname: Riethman
authors.affiliation: University of Pennsylvania, Perelman School of Medicine, Philadelphia, Pennsylvania, United States of America.|Columbia University, Mailman School of Public Health, New York, New York, United States of America.
authors.forename: Charles C
authors.initials: CC
authors.lastname: Branas
authors.affiliation: Dana Farber Cancer Institute and Harvard TH Chan School of Public Health, Boston, Massachusetts, United States of America.
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Rebbeck
mesh_terms: D000368:Aged; D006297:Health Services Accessibility; D006801:Humans; D007182:Income; D008297:Male; D008875:Middle Aged; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness / Q000473:pathology*; D011203:Poverty; D011471:Prostatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D012111:Residence Characteristics; D012307:Risk Factors; D012720:Severity of Illness Index; D012944:Social Support