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Clinical and Genetic Study of Prescription Opioid Addiction

处方阿片类药物成瘾的临床和遗传学研究

基本信息

批准号：
10180929
负责人：
Wade H Berrettini
金额：
$ 73.73万
依托单位：
GEISINGER CLINIC
依托单位国家：
美国
项目类别：
财政年份：
2017
资助国家：
美国
起止时间：
2017-09-01 至 2024-05-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/10180929
关键词：
Accounting Acupuncture Therapy Address Adult Agreement Appointment Back Pain Behavior Biological Blood specimen Brain Characteristics Chronic Clinical Clinical Research Collaborations Community Health Consent Contracts Counseling DNA Data Databases Development Disease Dose Drug Screening Electronic Health Record Emergency department visit Enrollment Ensure Epidemic Exposure to Foundations Genes Genetic Variation Genetic study Genomics Genotype Goals Grant Health system Image Individual Ingestion Institutes Integrated Delivery of Health Care Intervention Knowledge Laboratories Link Literature Medical Medical Genetics Medicine Monitor Morphine Musculoskeletal Pain Mutation Nerve Block Non-Malignant Opiate Addiction Opioid Oxycodone Pain Pain Clinics Participant Patient Self-Report Patients Pennsylvania Persons Pharmaceutical Preparations Pharmacologic Substance Pharmacotherapy Phenotype Physicians Population Preventive measure Primary Health Care Probability Public Health Questionnaires Recording of previous events Records Recurrence Reporting Research Resources Risk Risk Factors Sampling Services Source Standardization Structure System Terminology Testing United States Urine Variant Vicodin addiction base biobank candidate marker chronic musculoskeletal pain chronic pain chronic pain patient cohort economic cost exome exome sequencing genetic variant genome wide association study genomic data high risk medical specialties morphine equivalent multidisciplinary neuroimaging non-opioid analgesic opioid therapy opioid use opioid user pain patient patient population patients who use opioids personalized medicine phenotypic data predictive modeling prescription opioid prescription opioid addiction rare variant recruit relating to nervous system risk minimization skeletal tool

项目摘要

Opioid addiction (OA) is a multifactorial disease characterized by aberrant behavior related to obtaining and using opioids. It often arises from treatment of chronic pain patients with prescription opioid (PO) medications and is recognized as a major public health problem. The magnitude of the risk for developing OA remains controversial, because calculated rates suffer from imprecise and poorly defined terminology. This is underscored by the wide range of estimates of PO addiction (POA) in the literature which vary widely from 1% to > 40% of individuals treated long-term with POs for chronic non-progressive musculo-skeletal pain. Notably, there are few data on clinical characteristics and genetic variants that confer risk of POA. This project is focused on identifying the clinical, genetic, and neural characteristics which convey risk for POA. Towards this end, we have assembled a multi-disciplinary team to study a large patient population with a similar history of chronic non-progressive musculoskeletal pain and exposure to PO drugs. We will leverage the central biorepository and electronic health record (EHR) database of the Geisinger Health System to conduct large- scale genomics research and phenotype development. Through a collaboration with Regeneron Pharmaceuticals, the Geisinger biobank currently contains DNA samples on about 110,000 participants and includes both Illumina OmniExpressExome (HOEE) genotyping and whole exome sequence (WES) data, including common and rare variants, from over 60,000 of these subjects. This discovery cohort contains thousands of chronic musculoskeletal pain patients who have been taking greater than 120 mg-equivalents of morphine for more than 3 months and who are considered at high risk for developing POA. Using EHR and self-report tools to develop a case definition and quantitative scoring for POA, we will conduct a robust genome wide association study (GWAS). From the top GWAS candidates, we will identify nearby genes and use the WES data to search for rare variants that could contribute to POA. Using this information, we will derive a clinical/genetic profile of POA. This profile will be enhanced via integration of neuroimaging data. The on-going effort with Regeneron will yield genotype and WES data in a total of 250,000 participants over the next three years, providing additional samples for replication analyses. In the context of long-term opioid therapy, these results will permit identification of chronic non-progressive pain patients at risk for development of POA and provide the basis for preventative measures (non-opioid pharmacotherapy, regular counseling, frequent urine drug screens) and/or alternative pain specialty treatments (acupuncture, stimulators, nerve blocks). This personalized medicine approach will have major clinical impact by minimizing the risk for POA in the chronic pain population.

阿片成瘾（OA）是一种多因素疾病，其特征是与获取和使用相关的异常行为

项目成果

期刊论文数量（6）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Genetics and prescription opioid use (GaPO): study design for consenting a cohort from an existing biobank to identify clinical and genetic factors influencing prescription opioid use and abuse.

DOI：
10.1186/s12920-021-01100-z
发表时间：
2021-10-26
期刊：
BMC medical genomics
影响因子：
2.7
作者：
Troiani V;Crist RC;Doyle GA;Ferraro TN;Beiler D;Ranck S;McBryan K;Jarvis MA;Barbour JS;Han JJ;Ness RJ;Berrettini WH;Robishaw JD
通讯作者：
Robishaw JD

The use of the orbitofrontal H-sulcus as a reference frame for value signals.