Authors report no biomedical financial interests or potential conflicts of interest.
Article first published online: 16 DEC 2010
Copyright © 2010 Wiley-Liss, Inc.
American Journal of Medical Genetics Part B: Neuropsychiatric Genetics
Volume 156, Issue 2, pages 125–138, March 2011
How to Cite
Drgon, T., Johnson, C. A., Nino, M., Drgonova, J., Walther, D. M. and Uhl, G. R. (2011), “Replicated” genome wide association for dependence on illegal substances: Genomic regions identified by overlapping clusters of nominally positive SNPs. Am. J. Med. Genet., 156: 125–138. doi: 10.1002/ajmg.b.31143
How to Cite this Article: Drgon T, Johnson CA, Nino M, Drgonova J, Walther DM, Uhl GR. 2011. “Replicated” genome wide association for dependence on illegal substances: Genomic regions identified by overlapping clusters of nominally positive SNPs. Am J Med Genet Part B 156:125–138.
- Issue published online: 8 FEB 2011
- Article first published online: 16 DEC 2010
- Manuscript Accepted: 19 OCT 2010
- Manuscript Received: 20 JAN 2010
- NIH Intramural Research Program
- NIH Genes, Environment and Health Initiative (GEI). Grant Number: U01 HG004422
- Gene Environment Association Studies (GENEVA)
- GENEVA Coordinating Center U01. Grant Number: HG004446
- Collaborative Study on the Genetics of Alcoholism (COGA). Grant Number: U10 AA008401
- Collaborative Genetic Study of Nicotine Dependence (COGEND). Grant Number: P01 CA089392
- Family Study of Cocaine Dependence (FSCD). Grant Number: R01 DA013423
- Johns Hopkins University Center for Inherited Disease Research. Grant Number: U01HG004438
- National Institute on Alcohol Abuse and Alcoholism
- National Institute on Drug Abuse
- NIH Contract “High throughput genotyping for studying the genetic contributions to human disease”. Grant Number: HHSN268200782096C
- substance dependence;
Declaring “replication” from results of genome wide association (GWA) studies is straightforward when major gene effects provide genome-wide significance for association of the same allele of the same SNP in each of multiple independent samples. However, such unambiguous replication may be unlikely when phenotypes display polygenic genetic architecture, allelic heterogeneity, locus heterogeneity, and when different samples display linkage disequilibria with different fine structures. We seek chromosomal regions that are tagged by clustered SNPs that display nominally significant association in each of several independent samples. This approach provides one “nontemplate” approach to identifying overall replication of groups of GWA results in the face of difficult genetic architectures. We apply this strategy to 1 million (1M) SNP Affymetrix and Illumina GWA results for dependence on illegal substances. This approach provides high confidence in rejecting the null hypothesis that chance alone accounts for the extent to which clustered, nominally significant SNPs from samples of the same racial/ethnic background identify the same chromosomal regions. There is more modest confidence in: (a) identification of individual chromosomal regions and genes and (b) overlap between results from samples of different racial/ethnic backgrounds. The strong overlap identified among the samples with similar racial/ethnic backgrounds, together with prior work that identified overlapping results in samples of different racial/ethnic backgrounds, support contributions to individual differences in vulnerability to addictions that come from both relatively older allelic variants that are common in many current human populations and newer allelic variants that are common in fewer current human populations. © 2010 Wiley-Liss, Inc.