Genome-wide admixture mapping of DSM-IV alcohol dependence, criterion count, and the self-rating of the effects of ethanol in African American populations.
paper
Primary
Public
- Authors
- Lai, Dongbing; Kapoor, Manav; Wetherill, Leah; Schwandt, Melanie; Ramchandani, Vijay A; Goldman, David; Chao, Michael; Almasy, Laura; Bucholz, Kathleen; Hart, Ronald P; Kamarajan, Chella; Meyers, Jacquelyn L; Nurnberger, John I; Tischfield, Jay; Edenberg, Howard J; Schuckit, Marc; Goate, Alison; Scott, Denise M; Porjesz, Bernice; Agrawal, Arpana; Foroud, Tatiana
- Year
- 2021
- Journal
- American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
- PMID
- 32652861
- DOI
- 10.1002/ajmg.b.32805
- PMCID
- PMC9376735
African Americans (AA) have lower prevalence of alcohol dependence and higher subjective response to alcohol than European Americans. Genome-wide association studies (GWAS) have identified genes/variants associated with alcohol dependence specifically in AA; however, the sample sizes are still not large enough to detect variants with small effects. Admixture mapping is an alternative way to identify alcohol dependence genes/variants that may be unique to AA. In this study, we performed the first admixture mapping of DSM-IV alcohol dependence diagnosis, DSM-IV alcohol dependence criterion count, and two scores from the self-rating of effects of ethanol (SRE) as measures of response to alcohol: the first five times of using alcohol (SRE-5) and average of SRE across three times (SRE-T). Findings revealed a region on chromosome 4 that was genome-wide significant for SRE-5 (p value = 4.18E-05). Fine mapping did not identify a single causal variant to be associated with SRE-5; instead, conditional analysis concluded that multiple variants collectively explained the admixture mapping signal. PPARGC1A, a gene that has been linked to alcohol consumption in previous studies, is located in this region. Our finding suggests that admixture mapping is a useful tool to identify genes/variants that may have been missed by current GWAS approaches in admixed populations.
Genome-wide admixture mapping of SRE-5. Y-axis is the –log(P-value) for associations. X-axis is physical position of African ancestry blocks across the genome. The red horizontal line indicates genome-wide significance.
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| Name | Type |
|---|---|
| 1000 Genomes Project | cohort |
| AA cohorts | cohort |
| ADH1B | gene |
| admixture mapping association signal local | phenotype |
| African American | cohort |
| African American cohort from the National Institute on Alcohol Abuse and Alcoholism local | cohort |
| African ancestry allele local | variant |
| African ancestry blocks local | drug |
| African ancestry blocks local | variant |
| alcohol | phenotype |
| alcohol dependence | phenotype |
| alcohol-induced cellular toxicity local | phenotype |
| alcohol-related diseases | phenotype |
| alcohol sensitivity | phenotype |
| Alcohol Use | phenotype |
| Alcohol Use Disorder | phenotype |
| Alcohol Use Disorders Identification Test | phenotype |
| birth cohort local | phenotype |
| blood pressure | phenotype |
| brain | anatomy |
| CCDC149 local | gene |
| cellular toxicity local | phenotype |
| CEU | cohort |
| chr4:24,377,777-24,512,590 local | variant |
| chr4_GWS_region_variants local | variant |
| Chromosome 4 locus local | variant |
| cocaine | phenotype |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| Community comparison families | cohort |
| Consequences local | phenotype |
| CREB1 | gene |
| DHX15 local | gene |
| drinking | phenotype |
| Drinking-related problems local | phenotype |
| DSM-IV alcohol dependence | phenotype |
| DSM-IV alcohol dependence criterion count local | phenotype |
| ethanol consumption | phenotype |
| European ancestry | cohort |
| excessive alcohol consumption | phenotype |
| genetic variants | cohort |
| global African ancestry local | phenotype |
| heavy drinking | phenotype |
| Higher rates of recurrent and persistent alcohol dependence local | phenotype |
| Inflammation response local | phenotype |
| Kranzler et al 2019 local | cohort |
| Kranzler et al., 2019 | cohort |
| LGI2 local | gene |
| local African ancestry local | phenotype |
| Lower prevalence of alcohol dependence local | phenotype |
| marijuana | phenotype |
| mice | cohort |
| Million Veteran Project local | cohort |
| Million Veteran Project (MVP) local | cohort |
| mitochondrial dysfunction | phenotype |
| mortality | phenotype |
| N-acetylcysteine | drug |
| neuroendocrine response | phenotype |
| NHGRI-EBI GWAS catalog | cohort |
| NIAAA | cohort |
| NIAAA cohort local | cohort |
| NRF local | gene |
| obesity | phenotype |
| Obstructive sleep apnea local | phenotype |
| onset of drinking | phenotype |
| opioid | drug |
| other drug use | phenotype |
| phenotype | phenotype |
| PPARGC1A | gene |
| problematic alcohol use | phenotype |
| Progression to alcohol dependence local | phenotype |
| rats | cohort |
| Recurrent and persistent alcohol dependence local | phenotype |
| RFMix local | drug |
| rs10018808 local | variant |
| rs11931595 local | variant |
| rs1229984 | variant |
| rs2066702 | variant |
| rs3966916 local | variant |
| rs4770359 local | variant |
| rs72900220 local | variant |
| rs76004436 local | variant |
| rs79462764 local | variant |
| SAGE | cohort |
| sedatives | drug |
| Self-Rating of Effects of Ethanol questionnaire local | phenotype |
| sex | phenotype |
| SHAPEIT2 | drug |
| SOD3 local | gene |
| Spanish Mediterranean sample local | cohort |
| SRE | phenotype |
| SRE-5 score local | phenotype |
| SRE-5 scores local | phenotype |
| SRE questionnaire scores local | phenotype |
| SRE scores | phenotype |
| stimulants | drug |
| Stimulation response to alcohol local | phenotype |
| Stop drinking local | phenotype |
| stress | phenotype |
| Study of Addiction: Genetics and Environment | cohort |
| systemic lupus erythematosus | phenotype |
| United States | cohort |
| Walters et al., 2018 | cohort |
| Yale-Penn | cohort |
| YRI | cohort |
| Zemore et al., 2018 local | cohort |
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In this knowledge base
| Title | Year | PMID |
|---|---|---|
| Gene-based polygenic risk scores analysis of alcohol use disorder in African Americans. | 2022 | 35790736 |
External
| Title | Authors | Journal | Year | Link |
|---|---|---|---|---|
| Clinical, Genomic, and Neurophysiological Correlates of Lifetime Suicide Attempts among Individuals with an Alcohol Use Disorder. | Barr PB et al. | — | 2025 | → |
| Genetic influences on alcohol sensitivity: A critical review. | Yeung EW et al. | — | 2024 | → |
| Systematic comparison of phenome-wide admixture mapping and genome-wide association in a diverse biobank | Cullina S et al. | — | 2024 | — |
| The collaborative study on the genetics of alcoholism: Genetics. | Johnson EC et al. | — | 2023 | → |
| The Collaborative Study on the Genetics of Alcoholism: Overview. | Agrawal A et al. | — | 2023 | → |
| Gene-based polygenic risk scores analysis of alcohol use disorder in African Americans. | Lai D et al. | — | 2022 | → |
| Genome-wide association mapping of ethanol sensitivity in the Diversity Outbred mouse population. | Parker CC et al. | — | 2022 | → |
| Genomics and epigenomics of substance use disorders: An introduction. | Cormand B et al. | — | 2021 | → |