The utility of empirically assigning ancestry groups in cross-population genetic studies of addiction.
- Authors
- Peterson, Roseann E; Edwards, Alexis C; Bacanu, Silviu-Alin; Dick, Danielle M; Kendler, Kenneth S; Webb, Bradley T
- Year
- 2017
- Journal
- The American journal on addictions
- PMID
- 28714599
- DOI
- 10.1111/ajad.12586
- PMCID
- PMC5646819
BACKGROUND AND OBJECTIVES: Given moderate heritability and significant heterogeneity among addiction phenotypes, successful genome-wide association studies (GWAS) are expected to need very large samples. As sample sizes grow, so can genetic diversity leading to challenges in analyzing these data. Methods for empirically assigning individuals to genetically informed ancestry groups are needed. METHODS: We describe a strategy for empirically assigning ancestry groups in ethnically diverse GWAS data including extensions of principal component analysis (PCA) and population matching through minimum Mahalanobis distance. We apply these methods to data from Spit for Science (S4S): the University Student Survey, a study following college students longitudinally that includes genetic and environmental data on substance use and mental health (n = 7,603). RESULTS: The genetic-based population assignments for S4S were 48.7% European, 22.5% African, 10.4% Americas, 9.2% East Asian, and 9.2% South Asian descent. Self-reported census categories "More than one race" and "Unknown"as well as "Hawaiian/Pacific Islander" and "American-Indian/Native Alaskan" were empirically assigned representing a +9% sample retention over conventional methods. Although there was high concordance between self-reported race and empirical population-match (+.924), there was reduction in variance for most ancestry PCs for genetic-based population assignments. CONCLUSIONS: We were able to create more genetically homogenous groups and reduce sample and marker loss through cross-ancestry meta-analysis, potentially increasing power to detect etiologically relevant variation. Our approach provides a framework for empirically assigning genetic ancestry groups which can be applied to other ethnically diverse genetic studies. SCIENTIFIC SIGNIFICANCE: Given the important public health impact and demonstrable gains in statistical power from studying diverse populations, empirically sound practices for genetic studies are needed. (Am J Addict 2017;26:494-501).
1KGP population assignment. The first three principal components (PC) plotted for each of the 26 1KGP populations with Mahalanobis distance outliers marked in black.
1KGP super-population assignment. The first three PCs plotted for each of the 5 1KGP super-populations with Mahalanobis distance outliers marked in black.
S4S super-population assignment. The first three PCs plotted for each of the 5 genetic based super-populations determined using Mahalanobis distance.
The first three principal components (PC) plotted for self-reported census race and genetic super-population assignments. Comparison of self-reported census race and genetic super-population assignment plots indicate a reduction of variance in PCs for genetic based super-population assignments.
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