Trajectories of genetic risk across dimensions of alcohol use behaviors.
paper
Primary
Public
Preprint
- Authors
- Savage, Jeanne E; Aliev, Fazil; Barr, Peter B; Choi, Maia; Drouard, Gabin; Cooke, Megan E; Kuo, Sally I; Stephenson, Mallory; Brislin, Sarah J; Neale, Zoe E; Spit for Science Working Group, COGA Investigators; Latvala, Antti; Rose, Richard J; Kaprio, Jaakko; Dick, Danielle M; Meyers, Jacquelyn; Salvatore, Jessica E; Posthuma, Danielle
- Year
- 2025
- Journal
- medRxiv : the preprint server for health sciences
- PMID
- 40196263
- DOI
- 10.1101/2025.03.27.25324798
- PMCID
- PMC11974985
- Published as
- Trajectories of genetic risk across dimensions of alcohol use behaviors. →
BACKGROUND: Alcohol use behaviors (AUBs) manifest in a variety of normative and problematic ways across the life course, all of which are heritable. Twin studies show that genetic influences on AUBs change across development, but this is usually not considered in research identifying and investigating the genes linked to AUBs. AIMS: Understanding the dynamics of how genes shape AUBs could point to critical periods in which interventions may be most effective and provide insight into the mechanisms behind AUB-related genes. In this project, we investigate how genetic associations with AUBs unfold across development using longitudinal modelling of polygenic scores (PGSs). DESIGN: Using results from genome-wide association studies (GWASs), we created PGSs to index individual-level genetic risk for multiple AUB-related dimensions: , , a variable pattern of drinking associated with a preference for beer (), and externalizing behavior (). We created latent growth curve models and tested PGSs as predictors of latent growth factors (intercept, slope, quadratic) underlying trajectories of AUBs. SETTING: PGSs were derived in six longitudinal epidemiological cohorts from the US, UK, and Finland. PARTICIPANTS: Participant data were obtained from AddHealth, ALSPAC, COGA, FinnTwin12, the older Finnish Twin Cohort, and Spit for Science (total N = 19,194). These cohorts included individuals aged 14 to 67, with repeated measures collected over a span of 4 to 36 years. MEASUREMENTS: Primary measures included monthly frequency of typical alcohol consumption (CON) and heavy episodic drinking (HED). FINDINGS: Results indicated that higher PGSs for all AUBs are robustly associated with higher mean levels of CON and/or HED (B = 0.064-0.333, < 3.09E-04). However, these same genetic indices were largely not associated with drinking trajectories across cohorts. In the meta-analysis, only PGSs for chronic alcohol consistently predicted a steeper slope (increasing trajectory) of CON across time (B = 0.470, = 4.20E-06). CONCLUSIONS: The results indicate that genetic associations with AUBs not only differ between behaviors, but also across developmental time points and across cohorts. Genetic studies that take such heterogeneity into account are needed to better represent the underlying etiology of AUBs. Individual-level genetic profiles may be useful to point to personalized intervention timelines, particularly for individuals with high alcohol genetic risk scores.
Mean levels per age of A) typical consumption and B) heavy episodic drinking frequencies in five longitudinal cohorts and C) multiple alcohol use behaviors in the older FinnTwin Cohort.
Schematic of the latent growth curve (LGC) model used to estimate the effects of polygenic scores (PGSs) on trajectories of alcohol use behaviors.
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| Name | Type |
|---|---|
| 1000 Genomes EUR reference panel local | drug |
| Add Health | cohort |
| adulthood | cohort |
| adult probands local | cohort |
| alcohol | phenotype |
| alcohol abuse | phenotype |
| alcohol dependence | phenotype |
| alcohol metabolism genes | gene |
| Alcohol Problems | phenotype |
| alcohol sensitivity | phenotype |
| alcohol-specific genes local | gene |
| Alcohol Use | phenotype |
| alcohol use disorders | phenotype |
| ALSPAC | cohort |
| ancestry principal components | drug |
| AUB-related genes local | gene |
| average consumption frequency/quantity local | phenotype |
| average frequency local | phenotype |
| beer | drug |
| BeerPref local | drug |
| BeerPref local | phenotype |
| BeerPref PGS local | phenotype |
| BeerPref PGS local | variant |
| chronic and severe alcohol Problems local | phenotype |
| Collaborative Study on the Genetics of Alcoholism (COGA) | cohort |
| community-ascertained comparison families local | cohort |
| CON | phenotype |
| CON PGS local | phenotype |
| consumption | phenotype |
| Consumption local | drug |
| Consumption frequency local | phenotype |
| Consumption PGS local | phenotype |
| Consumption PGS local | variant |
| co-occurring disorders local | phenotype |
| current consumption quantity local | phenotype |
| drinking | phenotype |
| dynamic AUB measures local | phenotype |
| early substance use | phenotype |
| ethanol consumption | phenotype |
| European population | cohort |
| EUR participants | cohort |
| EXT local | drug |
| EXT | phenotype |
| externalizing behavior | phenotype |
| Externalizing behavior PGS local | variant |
| EXT PGS | phenotype |
| EXT PGS local | variant |
| EXT-related genes local | gene |
| Finland Central Population Registry local | cohort |
| Finnish Twin Cohort (born 1983-1987) local | cohort |
| Finntwin12 | cohort |
| first 5 cohorts local | cohort |
| frequency of alcohol use | phenotype |
| FTC local | cohort |
| FTC local | phenotype |
| FTC cohort local | cohort |
| FTC PGS local | phenotype |
| FTC sample local | cohort |
| genetic sex local | drug |
| gEtOH local | phenotype |
| hard liquor local | drug |
| Heavy local | phenotype |
| heavy drinking | phenotype |
| Heavy drinking (HED) local | phenotype |
| heavy (episodic) drinking local | phenotype |
| Heavy episodic drinking frequency local | phenotype |
| HED | phenotype |
| HED PGS local | phenotype |
| high-risk families | cohort |
| impulsivity | phenotype |
| increasing alcohol use/problems over time local | phenotype |
| intercept | phenotype |
| International longitudinal cohorts local | cohort |
| intoxication | phenotype |
| LGC local | cohort |
| lifetime AUD diagnoses local | phenotype |
| middle adulthood | phenotype |
| nicotine dependence | phenotype |
| older adulthood local | phenotype |
| older cohort | cohort |
| older FTC local | cohort |
| overall quantity and frequency of Consumption of varied alcoholic beverage types local | phenotype |
| PassOut local | phenotype |
| PassOut frequency local | phenotype |
| past-year alcohol problems local | phenotype |
| patterns of AUBs local | phenotype |
| PGs | drug |
| PLINK2 local | drug |
| polygenic risk score | cohort |
| problems | phenotype |
| Problems local | drug |
| Problems PGS local | phenotype |
| Problems PGS local | variant |
| Problems PGSs local | phenotype |
| prospective sample local | cohort |
| PRS-CS | drug |
| quadratic factor local | phenotype |
| rare and structural variants local | variant |
| S4S study local | cohort |
| slope | phenotype |
| smoking behavior | phenotype |
| social drinking habits local | phenotype |
| spirits | drug |
| Spit for Science | cohort |
| static AUB measures local | phenotype |
| study cohort | cohort |
| substance use | phenotype |
| Twin cohort | cohort |
| wine | drug |
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