title: Polygenic risk scores for cigarettes smoked per day do not generalize to a Native American population.
abstract: Recent studies have demonstrated the utility of polygenic risk scores (PRSs) for exploring the genetic etiology of psychiatric phenotypes and the genetic correlations between them. To date, these studies have been conducted almost exclusively using participants of European ancestry, and thus, there is a need for similar studies conducted in other ancestral populations. However, given that the predictive ability of PRSs are sensitive to differences in linkage disequilibrium (LD) patterns and minor allele frequencies across discovery and target samples, the applicability of PRSs developed in European ancestry samples to other ancestral populations has yet to be determined. Therefore, the current study derived PRSs for cigarettes per day (CPD) from predominantly European-ancestry samples and examined their ability to predict nicotine dependence (ND) in a Native American (NA) population sample.
  
  
  
  Results from the Tobacco and Genetics Consortium's meta-analysis of genome-wide association studies of CPD were used to compute PRSs in a NA community sample (N=288). These scores were then used to predict ND diagnostic status.
  
  
  
  The PRS was not significantly associated with liability for ND in the full sample. However, a significant interaction between PRS and percent NA ancestry was observed. Risk scores were positively associated with liability for ND at higher levels of European ancestry, but no association was observed at higher levels of NA ancestry.
  
  
  
  These findings illustrate how differences in patterns of LD across discovery and target samples can reduce the predictive ability of PRSs for complex traits.
authors.affiliation: Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211, United States.
authors.forename: Jacqueline M
authors.initials: JM
authors.lastname: Otto
authors.affiliation: Department of Psychological Sciences, University of Missouri, 210 McAlester Hall, Columbia, MO 65211, United States.
authors.forename: Ian R
authors.initials: IR
authors.lastname: Gizer
authors.affiliation: Renaissance Computing Institute (RENCI), 100 Europa Drive, Suite 540, Chapel Hill, NC 27517, United States.
authors.forename: Chris
authors.initials: C
authors.lastname: Bizon
authors.affiliation: Renaissance Computing Institute (RENCI), 100 Europa Drive, Suite 540, Chapel Hill, NC 27517, United States; Departments of Genetics and Neurology, University of North Carolina at Chapel Hill, 120 Mason Farm Road, 5093 Genetic Medicine Building, CB#7264, Chapel Hill, NC 27599, United States.
authors.forename: Kirk C
authors.initials: KC
authors.lastname: Wilhelmsen
authors.affiliation: Department of Molecular and Cellular Neurosciences, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, United States. Electronic address: cindye@Scripps.edu.
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Ehlers
mesh_terms: D000328:Adult; D005260:Female; D005787:Gene Frequency; D055106:Genome-Wide Association Study; D006801:Humans; D007198:Indians, North American / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D015201:Meta-Analysis as Topic; D020412:Multifactorial Inheritance; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000235:genetics*; D062789:Tobacco Products / Q000706:statistics & numerical data; D014029:Tobacco Use Disorder / Q000235:genetics*; D044465:White People / Q000235:genetics*
keywords: American Indian; Genetic association; Nicotine dependence; Polygenic; Smoking