Identifying genetic sources of comorbidity between cannabis and schizophrenia using genome-wide and integrative omics data

使用全基因组和综合组学数据识别大麻和精神分裂症之间共病的遗传来源

基本信息

  • 批准号:
    10594423
  • 负责人:
  • 金额:
    $ 15.73万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2021
  • 资助国家:
    美国
  • 起止时间:
    2021-04-01 至 2026-03-31
  • 项目状态:
    未结题

项目摘要

Project Summary Recreational cannabis use is becoming increasingly common in the United States, even within vulnerable populations. Amidst growing concerns surrounding the possible adverse consequences of chronic cannabis use, there is evidence that cannabis use disorder (CUD) is genetically correlated with susceptibility to several behavioral (e.g., lower educational achievement) and psychiatric (e.g., schizophrenia) outcomes, thus bringing into question prior causal claims. The most aggressively contested discussion surrounds the role of cannabis use and CUD in the etiology of schizophrenia (SCZ) and psychotic illness. While there is now an abundance of evidence supporting shared genetic influences, studies also outline the psychotomimetic effects of especially high potency forms of tetrahydrocannabinol (THC). A systematic search for pleiotropic variants that undergird this comorbidity between CUD and SCZ can not only provide insights into shared biology, but also outline avenues for identifying subgroups of individuals at greatest risk. This Mentored Research Scientist Development Award (K01) proposes a research plan that leverages some of the largest currently available genome-wide association study (GWAS) datasets to (a) conduct a cross-disorder GWAS of CUD with SCZ, and to contrast it with findings from a similar cross-disorder analysis of cannabis use with SCZ, to identify loci of convergent and divergent effect; (b) to test for a causal relationship using a genetically-informed approach and harness curated `omics data from human and rodent models of cannabis exposure and SCZ, to fine-map significant loci and further prioritize causal variants for biological plausibility; and (c) to utilize polygenic risk scores derived from these cross-disorder analyses to identify associations with first-episode psychosis, cannabis-induced psychosis, and childhood psychosis-proneness in independent samples. These research aims are founded on four key training objectives that will enhance the applicant's career goal of becoming an NIH-funded independent investigator who works at the interface of addictions and psychiatric illness. These training objectives include (a) a deep understanding of the clinical effects of acute and chronic exposure to cannabis, (b) integrative bioinformatics approaches for post-GWAS annotation, including cross-species data (c) an appreciation of the neurobiology underlying the comorbidity between cannabis and SCZ, and (d) career development towards leadership and mentorship positions. The applicant builds upon her current funding and training directed at advanced statistical genetics to addressing comorbidity by adding on novel facets relating more broadly to multi- omics data integration and more specifically to the unique yet ubiquitous comorbidity between cannabis and SCZ. Together, this training and research plan will produce some of the first insights into the shared genetic etiology underlying CUD and SCZ and provide opportunities for functionally targeted future studies, with the ultimate objective of producing therapeutic alternatives that can partially mitigate the serious personal costs of chronic cannabis use in SCZ patients.
项目总结

项目成果

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Emma Covey Johnson其他文献

Emma Covey Johnson的其他文献

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{{ truncateString('Emma Covey Johnson', 18)}}的其他基金

Using genomics and extensive phenotyping to dissect the relationships between substance use disorders and chronic pain
利用基因组学和广泛的表型分析来剖析物质使用障碍和慢性疼痛之间的关系
  • 批准号:
    10797779
  • 财政年份:
    2023
  • 资助金额:
    $ 15.73万
  • 项目类别:
Identifying genetic sources of comorbidity between cannabis and schizophrenia using genome-wide and integrative omics data
使用全基因组和综合组学数据识别大麻和精神分裂症之间共病的遗传来源
  • 批准号:
    10364741
  • 财政年份:
    2021
  • 资助金额:
    $ 15.73万
  • 项目类别:
Identifying genetic sources of comorbidity between cannabis and schizophrenia using genome-wide and integrative omics data
使用全基因组和综合组学数据识别大麻和精神分裂症之间共病的遗传来源
  • 批准号:
    10215104
  • 财政年份:
    2021
  • 资助金额:
    $ 15.73万
  • 项目类别:

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