Genomic regions identified by overlapping clusters of nominally-positive SNPs from genome-wide studies of alcohol and illegal substance dependence.
paper
Primary
Public
- Authors
- Johnson, Catherine; Drgon, Tomas; Walther, Donna; Uhl, George R
- Year
- 2011
- Journal
- PloS one
- PMID
- 21818250
- DOI
- 10.1371/journal.pone.0019210
- PMCID
- PMC3144872
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 is 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 M SNP GWA results for dependence on: a) alcohol (including many individuals with dependence on other addictive substances) and b) at least one illegal substance (including many individuals dependent on alcohol). 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 sets of chromosomal regions. It identifies several genes that are also reported in other independent alcohol-dependence GWA datasets. There is more modest confidence in: a) identification of individual chromosomal regions and genes that are not also identified by data from other independent samples, b) the more modest overlap between results from samples of different racial/ethnic backgrounds and c) the extent to which any gene not identified herein is excluded, since the power of each of these individual samples is modest. Nevertheless, the strong overlap identified among the samples with similar racial/ethnic backgrounds supports contributions to individual differences in vulnerability to addictions that come from newer allelic variants that are common in subsets of current humans.
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| Name | Type |
|---|---|
| abilities to quit smoking local | phenotype |
| Ability to quit smoking | phenotype |
| Acute response to alcohol local | phenotype |
| addiction | phenotype |
| addiction phenotypes | phenotype |
| Addictive Substance local | drug |
| ADH1C | gene |
| adoption studies | cohort |
| Affymetrix | drug |
| Affymetrix 6.0 arrays local | drug |
| Affymetrix 6.0 SNPs local | variant |
| African American | cohort |
| African-American control subjects local | cohort |
| African American data local | cohort |
| African American dataset local | cohort |
| African-American dependent subjects local | cohort |
| African-Americans | cohort |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| alcohol metabolism | phenotype |
| Asian | cohort |
| autosomal SNPs | cohort |
| bipolar disorder | phenotype |
| CADPS local | gene |
| case cohort | cohort |
| cases | cohort |
| case samples | cohort |
| CAST | gene |
| CDH13 | gene |
| CDH13 variant local | variant |
| Center for Inherited Disease Research (CIDR) local | cohort |
| chromosomal clustering local | phenotype |
| cigarettes | phenotype |
| cocaine | phenotype |
| COGEND | cohort |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| complex disorders | phenotype |
| control | cohort |
| controls | cohort |
| Control samples local | phenotype |
| control subjects | cohort |
| CSMD1 | gene |
| dbGaP | cohort |
| dbGAP African-Americans local | cohort |
| dbGAP European-Americans local | cohort |
| dbGAP European-American samples local | cohort |
| dbGAP individuals local | cohort |
| dbGAP samples | cohort |
| dbGAP study phs000092.v1.p1 local | cohort |
| dbGap variable phv00022939.v1.p1.c2 local | cohort |
| dependence | phenotype |
| disease | phenotype |
| disorder | phenotype |
| DSCAM local | gene |
| ERAP local | gene |
| European-American control subjects local | cohort |
| European-American dataset local | cohort |
| European-American dependent subjects local | cohort |
| European ancestry | cohort |
| European population | cohort |
| families | cohort |
| Family study of cocaine dependence (FSCD) local | cohort |
| FTND >4 local | phenotype |
| FTND score >4 local | phenotype |
| FTND scores >4 local | phenotype |
| full sample | cohort |
| functional allelic variant local | variant |
| GABA receptor gene cluster local | gene |
| gene | gene |
| genes | gene |
| Genome-wide association data local | cohort |
| GWA datasets | cohort |
| GWA study | cohort |
| heavy drinking | phenotype |
| Hispanic individuals | cohort |
| illegal behaviors | phenotype |
| Illegal substance use local | phenotype |
| illicit drug dependence | phenotype |
| illicit drug use | phenotype |
| Illumina 1 M SNP arrays local | drug |
| Illumina genotyping | drug |
| Illumina platform | drug |
| independent samples | cohort |
| linkage studies | cohort |
| marijuana | phenotype |
| marijuana dependence | phenotype |
| MNB local | cohort |
| MNB/NIDA European-American local | cohort |
| Modest substance use local | phenotype |
| Monte Carlo simulation local | cohort |
| Mtmr7 | gene |
| nicotine | drug |
| nicotine dependence | phenotype |
| NIDA | cohort |
| NIDA/MNB | cohort |
| NIDA/MNB African-American samples local | cohort |
| NIDA/MNB European American samples local | cohort |
| NIDA/MNB European-American samples local | cohort |
| NIDA/MNB pooled samples local | cohort |
| NIDA/MNB samples local | cohort |
| NIDA pooled samples local | cohort |
| NIDA samples local | cohort |
| nontemplate analyses local | drug |
| oligogenic loci local | gene |
| opioid | drug |
| opioid dependence | phenotype |
| PECR | gene |
| phenotype | phenotype |
| phenotypic differences | phenotype |
| physical abuse | phenotype |
| polygenic influences | cohort |
| polygenic influences local | phenotype |
| pseudopositive SNPs local | variant |
| samples | cohort |
| smoking | phenotype |
| SNP | cohort |
| SNP clusters local | variant |
| substance abuse | phenotype |
| substance use | phenotype |
| Treatment-seeking individuals local | phenotype |
| true positive SNPs local | variant |
| Twin cohort | cohort |
| UBASH3B local | gene |
| unspecified phenotype local | phenotype |
| variant | cohort |
| Vulnerability to Develop Dependence local | phenotype |
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