title: Replication and heritability of prostate cancer risk variants: impact of population-specific factors.
abstract: BACKGROUND
  Prostate cancer incidence and mortality rates vary across populations, with African American men exhibiting the highest rates. To date, genome-wide association studies have identified 104 SNPs independently associated with prostate cancer in men of European ancestry.
  
  
  METHODS
  We investigated whether the ability to replicate findings for these 104 SNPs in African American, Asian, and Latino populations depends on variation in risk allele frequencies (RAF), strength of associations, and/or patterns of linkage disequilibrium (LD) at the associated loci. We extracted estimates of effect from the literature, and determined RAF and LD information across the populations from the 1000 Genomes Project.
  
  
  RESULTS
  Risk variants were largely replicated across populations. Relative to Europeans, 83% had smaller effect sizes among African Americans and 73% demonstrated smaller effect sizes among Latinos. Among Asians, however, 56% showed larger effect sizes than among Europeans. The largest difference in RAFs was observed between European and African ancestry populations, but this difference did not impact our ability to replicate. The extent of LD within 250 kb of risk loci in Asian ancestry populations was suggestively lower for variants that did not replicate (P = 0.013).
  
  
  CONCLUSIONS
  Despite substantial overlap in prostate cancer risk SNPs across populations, the variation in prostate cancer incidence among different populations may still in part reflect unique underlying genetic architectures.
  
  
  CONCLUSIONS
  Studying different ancestral populations is crucial for deciphering the genetic basis of prostate cancer.
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, California. Department of Biology, Ecole Normale Supérieure de Lyon, Lyon, France.
authors: Victor
authors: V
authors: Virlogeux
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, California.
authors: Rebecca E
authors: RE
authors: Graff
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, California. Institute for Human Genetics, University of California, San Francisco, California.
authors: Thomas J
authors: TJ
authors: Hoffmann
authors: Department of Epidemiology and Biostatistics, University of California, San Francisco, California. Institute for Human Genetics, University of California, San Francisco, California. Department of Urology, University of California, San Francisco, California. UCSF Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, California. jwitte@ucsf.edu.
authors: John S
authors: JS
authors: Witte
mesh_terms: D001741:Black or African American / Q000235:genetics; D044466:Asian People / Q000235:genetics; D005006:Ethnicity / Q000235:genetics*; D005500:Follow-Up Studies; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D011471:Prostatic Neoplasms / Q000208:ethnology* / Q000235:genetics*; D015203:Reproducibility of Results; D012307:Risk Factors; D014481:United States / Q000453:epidemiology; D044465:White People / Q000235:genetics