ArticleAlcoholism, clinical and experimental research2018
Incorporating Functional Genomic Information to Enhance Polygenic Signal and Identify Variants Involved in Gene-by-Environment Interaction for Young Adult Alcohol Problems.
Article in Alcoholism, clinical and experimental research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.
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Who cites it
7 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- Systematic Review of Polygenic Gene-Environment Interaction in Tobacco, Alcohol, and Cannabis Use.Behavior genetics · 2019Pooled it
- Polygenic Score for Smoking is associated with Externalizing Psychopathology and Disinhibited Personality Traits but not Internalizing Psychopathology in Adolescence.Clinical psychological science : a journal of the Association for Psychological Science · 2021Article
- Using Genetic Marginal Effects to Study Gene-Environment Interactions with GWAS Data.Behavior genetics · 2021Article
- Article
- Recent Efforts to Dissect the Genetic Basis of Alcohol Use and Abuse.Biological psychiatry · 2020Review
- Psychosocial moderation of polygenic risk for cannabis involvement: the role of trauma exposure and frequency of religious service attendance.Translational psychiatry · 2019Article
- FinnTwin12 Cohort: An Updated Review.Twin research and human genetics : the official journal of the International Society for Twin Studies · 2019Review
Corrections and comments
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Authors and funding
11 authors at 5 institutions in 3 countries.
Funding
Abstract
backgroundCharacterizing aggregate genetic risk for alcohol misuse and identifying variants involved in gene-by-environment (G × E) interaction effects has so far been a major challenge. We hypothesized that functional genomic information could be used to enhance detection of polygenic signal underlying alcohol misuse and to prioritize identification of single nucleotide polymorphisms (SNPs) most likely to exhibit G × E effects.
methodsWe examined these questions in the young adult FinnTwin12 sample (n = 1,170). We used genomewide association estimates from an independent sample to derive 2 types of polygenic scores for alcohol problems in FinnTwin12. Genomewide polygenic scores included all SNPs surpassing a designated p-value threshold. DNase polygenic scores were a subset of the genomewide polygenic scores including only variants in DNase I hypersensitive sites (DHSs), which are open chromatin marks likely to index regions with a regulatory function. We conducted parallel analyses using height as a nonpsychiatric model phenotype to evaluate the consistency of effects. For the G × E analyses, we examined whether SNPs in DHSs were overrepresented among SNPs demonstrating significant G × E effects in an interaction between romantic relationship status and intoxication frequency.
resultsContrary to our expectations, we found that DNase polygenic scores were not more strongly predictive of alcohol problems than conventional polygenic scores. However, variants in DNase polygenic scores had per-SNP effects that were up to 1.4 times larger than variants in conventional polygenic scores. This same pattern of effects was also observed in supplementary analyses with height. In G × E models, SNPs in DHSs were modestly overrepresented among SNPs with significant interaction effects for intoxication frequency.
conclusionsThese findings highlight the potential utility of integrating functional genomic annotation information to increase the signal-to-noise ratio in polygenic scores and identify genetic variants that may be most susceptible to environmental modification.
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