Concurrent substance use and psychiatric disorders: a pipeline to investigate shared genomic liability and causal effects

Ended Project Grant Awarded Last action

Award ID
R21DA057542
Recipient
Awarding agency
Obligated
$431,403

Award facts

Assistance listing
93.279 Drug Use and Addiction Research Programs
Completion date
Originally
Place of performance
2323 Riverside Dr., Ottawa, ON K1H 1A1, Canada

Award details come from USAspending.gov.

Description

As the agency reported it.

Abstract
Substance use and other psychiatric disorders result in enormous personal, healthcare, and economic costs. Substance use (e.g., tobacco use disorder) and psychiatric (e.g., schizophrenia) disorders are highly comorbid. Three main theories have been proposed to explain the high comorbidity of tobacco use and schizophrenia: 1) self-medication (e.g., schizophrenia promotes tobacco use due to nicotine's effect on reducing cognitive deficits and medication side effects), 2) tobacco use causes schizophrenia, and 3) a shared liability, due to shared genetic and environmental factors. Tobacco use and schizophrenia are each highly heritable (~60- 80%) and we and others have shown that they share several common genetic risk factors. Two traits may share genetic risk factors due pleiotropy (i.e., a gene variant influences both traits) or because one disorder causes the other. Furthermore, shared genetic risk may be present in all individuals (i.e., whole-group pleiotropy) or may be restricted to a subset of individuals (i.e., sub-group heterogeneity). Using our expertise in tobacco use, biomarkers, schizophrenia, statistical genetics, and transcriptional analyses, we will develop a comprehensive analytic pipeline to elucidate the shared genomic liability of tobacco use and schizophrenia, and identify potential causal effects. Our study improves upon initial cross-disorder analyses, and involves 1) obtaining data from the largest available genomics datasets of schizophrenia and tobacco use, 2) examining genetic correlation between the traits, 3) identifying shared genetic variants, 4) examining biological (i.e., mechanistic) pathways, 5) exploring functional effects of the shared genetic variants, and 6) testing causal directions and effects of whole-group pleiotropy versus sub-group heterogeneity. In aim 1, we will become proficient in all 6 steps of the analytic pipeline by analyzing women and men together. In aim 2, we will conduct genome-wide SEX-based analyses of tobacco use to determine the feasibility of using SEX-based genomic analyses in future investigations of concurrent psychiatric disorders. To develop the pipeline, we will use nicotine intake biomarkers, which capture tobacco use more accurately than self-reported measures. However, gwas of self-reported traits or diagnostic criteria could be used when biomarkers are unavailable. This grant will train the young investigator PI for a larger genomics program investigating the shared genomic liability and causality between other pairs of heritable and concurrent psychiatric disorders. We will apply this pipeline to diverse populations as the datasets become available. Through these efforts, we will better understand the biological vulnerability to developing CO-occurring substance use and psychiatric disorders. This work may lead to improved prevention and treatment approaches, as well as reveal novel targets for drug discovery.

Transactions

Action Obligated Date
Amendment $0
Amendment $144,521
Amendment $0
Amendment $0
Amendment $143,441
Original award $143,441

Quick answers

Who received award R21DA057542?

R21DA057542 was awarded to Centre For Addiction And Mental Health by National Institute on Drug Abuse (National Institutes of Health) on September 1, 2023.

How much is award R21DA057542 worth?

$431,403 has been obligated on R21DA057542.

On GovTribe

See this award's full record

  • Every transaction and subaward
  • The recipient's other awards and teaming partners
  • Similar grant awards
  • Ask GovTribe AI about this award
Try for free Login