Does polygenic risk for substance-related traits predict ages of onset and progression of symptoms?
Age of onset
alcohol use disorder
milestones
opioid use disorder
polygenic risk scores
prediction
progression measures
smoking
Journal
Addiction (Abingdon, England)
ISSN: 1360-0443
Titre abrégé: Addiction
Pays: England
ID NLM: 9304118
Informations de publication
Date de publication:
09 2023
09 2023
Historique:
received:
26
10
2022
accepted:
25
03
2023
pmc-release:
01
09
2024
medline:
8
8
2023
pubmed:
18
4
2023
entrez:
17
4
2023
Statut:
ppublish
Résumé
Genetic risk can influence disease progression. We measured the impact of genetic risk for substance use disorders (SUDs) on substance use onset and progression of symptoms. Using findings from genome-wide association studies (GWASs) of alcohol use disorder (AUD), opioid use disorder (OUD) and smoking trajectory (SMK) as discovery samples, we calculated polygenic risk scores (PRSs) in a deeply phenotyped independent target sample. Participants in the target sample were recruited from 2000 to 2020 from US inpatient or outpatient settings or through advertisements and comprised 5692 European-ancestry individuals (EUR) (56.2% male) and 4918 African-ancestry individuals (AFR) (54.9% male). This study measured age of first substance use, regular use, reported problems and dependence diagnosis and progression from regular use to onset of problems and dependence for alcohol, opioids and smoking. We examined the contribution of PRS to each milestone and progression measure. EUR and males reported an earlier onset and shorter progression times than AFR and females, respectively. Among EUR, higher AUD PRS predicted earlier onset and more rapid progression to alcohol-related milestones (P < 0.001). Although the AUD PRS was a stronger moderator of problem onset among females (P = 0.017), it was more predictive of the progression to problems among males (P = 0.005). OUD and SMK PRS in EUR also predicted earlier onset of the respective milestones (P < 0.001). Among AFR, where power is lower due to the smaller discovery sample, AUD PRS predicted age of regular alcohol use (P = 0.039) and dependence (P = 0.001) and progression from regular use to diagnosis (P = 0.045), while SMK PRS predicted earlier age of initiation (P = 0.036). Genetic risk for SUDs appears to predict substance use milestones and symptom progression among European-ancestry individuals and, to a lesser extent, African-ancestry individuals.
Sections du résumé
BACKGROUND AND AIMS
Genetic risk can influence disease progression. We measured the impact of genetic risk for substance use disorders (SUDs) on substance use onset and progression of symptoms.
DESIGN, SETTING, PARTICIPANTS
Using findings from genome-wide association studies (GWASs) of alcohol use disorder (AUD), opioid use disorder (OUD) and smoking trajectory (SMK) as discovery samples, we calculated polygenic risk scores (PRSs) in a deeply phenotyped independent target sample. Participants in the target sample were recruited from 2000 to 2020 from US inpatient or outpatient settings or through advertisements and comprised 5692 European-ancestry individuals (EUR) (56.2% male) and 4918 African-ancestry individuals (AFR) (54.9% male).
MEASUREMENTS
This study measured age of first substance use, regular use, reported problems and dependence diagnosis and progression from regular use to onset of problems and dependence for alcohol, opioids and smoking. We examined the contribution of PRS to each milestone and progression measure.
FINDINGS
EUR and males reported an earlier onset and shorter progression times than AFR and females, respectively. Among EUR, higher AUD PRS predicted earlier onset and more rapid progression to alcohol-related milestones (P < 0.001). Although the AUD PRS was a stronger moderator of problem onset among females (P = 0.017), it was more predictive of the progression to problems among males (P = 0.005). OUD and SMK PRS in EUR also predicted earlier onset of the respective milestones (P < 0.001). Among AFR, where power is lower due to the smaller discovery sample, AUD PRS predicted age of regular alcohol use (P = 0.039) and dependence (P = 0.001) and progression from regular use to diagnosis (P = 0.045), while SMK PRS predicted earlier age of initiation (P = 0.036).
CONCLUSIONS
Genetic risk for SUDs appears to predict substance use milestones and symptom progression among European-ancestry individuals and, to a lesser extent, African-ancestry individuals.
Identifiants
pubmed: 37069489
doi: 10.1111/add.16210
pmc: PMC10525011
mid: NIHMS1902950
doi:
Substances chimiques
Ethanol
3K9958V90M
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, U.S. Gov't, Non-P.H.S.
Langues
eng
Sous-ensembles de citation
IM
Pagination
1675-1686Subventions
Organisme : NIAAA NIH HHS
ID : K01 AA028292
Pays : United States
Organisme : NIDA NIH HHS
ID : P30 DA046345
Pays : United States
Organisme : NIAAA NIH HHS
ID : R01 AA026364
Pays : United States
Organisme : NIDA NIH HHS
ID : R01 DA018432
Pays : United States
Informations de copyright
© 2023 Society for the Study of Addiction.
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