Genetic risk factors for opioid use disorder have been identified

Summary: A new, large-scale, genome-wide association study has identified 18 new genetic risk factors for opioid use disorder, raising the number of genes associated with OUD from 1-19.

source: Yale

A new human genomics study led by Yale University scientists has identified genetic risk factors for opioid use disorder (OUD) and related substance use disorders according to a new large-scale genome-wide association study — increasing the number of known risk genes from 1 to 19.

This action comes as opioid-related overdoses have reached an all-time high in the United States and continue to rise worldwide. The results are published in Molecular Psychiatry, meeting an urgent need where genetic discovery of agarwood has been limited in recent years. Genetic discovery leads to a better understanding of biology.

Senior author Joel Gelinter, MD, professor of psychiatry at Foundation Trust and professor of genetics and neuroscience at Yale University, said little is known about the specific genetic factors that influence recurrence risk.

In this study, the researchers worked to increase knowledge of OUD genetics by completing a meta-analysis of OUD—that is, pooling data from many different studies—and then by incorporating genetic information from other related substance use disorders for greater gene discovery capacity.

The researchers examined the genetic data of more than 600,000 participants of European and African genetic ancestry, providing more information than previous studies on OUD risk variance.

Scientists have identified genetic variation in 19 genes associated with OUD risk; OPRM1 and FURIN were two genes identified in the analysis of OUD alone, with several genes identified in the analysis that included information from OUD along with cannabis use disorder and alcohol use disorder.

“OPRM1 is a gene that encodes mu opioid receptors in the brain making it a major genetic possibility for OUD—previous work has shown that variation in this gene influences OUD risk. Our challenge has been to bypass OPRM1,” Gellerenter said.

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This action comes as opioid-related overdoses have reached an all-time high in the United States and continue to rise worldwide. The image is in the public domain

“Our efforts brought in as much data as possible at the genome level. We wanted to collect as many data sets and samples as possible,” said Joseph Dick, PhD, a postdoctoral fellow in the Department of Psychiatry in the Yale University Department of Human Genetics and first author of the research paper.

We believe that our findings have identified genetic risks specific to OUD as well as genetic risks more broadly shared with other types of substance use disorders. This is consistent with previous studies showing specific genetic effects of some drugs as well as a shared genetic responsibility for substance use disorders on a larger scale. “

The findings also reveal genetic links between the development of recurrence and related conditions such as chronic pain and inability to function due to illness or disability, and other psychological outcomes such as anxiety, depression and post-traumatic stress disorder.

“These genetic findings are in line with the common features often seen in the clinical presentation of individuals diagnosed with OUD. We found that genetic overlap,” Dick said.

We know that there are many factors that influence the risk of substance use disorders such as audacity. These results do not suggest that anyone with these genetic risk factors should or should be prescribed to deal with pain or anything like that; This work does not support this conclusion, but it may help explain some of the unanswered questions as we continue to expand on these findings in hopes of helping address public health concerns related to opioids.

About this research on genetics and addiction news

author: Christopher Gardner
source: Yale
Contact: Christopher Gardner – Yale
picture: The image is in the public domain

original search: open access.
A genome-wide association study in individuals of European and African descent and a multi-trait analysis of opioid use disorder identifies 19 independent genome-wide risk loci.Written by Joseph D. Dick et al. Molecular Psychiatry


Summary

A genome-wide association study in individuals of European and African descent and a multi-trait analysis of opioid use disorder identifies 19 independent genome-wide risk loci.

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Despite the significant toll of opioid use disorder (OUD), genome-wide association studies (GWAS) of agarwood (OUD) to date have yielded few allergy loci.

We have performed large-scale GWAS of OUD in individuals of European (EUR) and African (AFR) ancestry, improving genetic information by performing MTAG (multiple trait analysis of GWAS) with genetically related substance use disorders (SUDs).

The meta-analysis included seven groups: the Million Veteran Program, Psychogenomics Consortium, iPSYCH, FinnGen, Partners Biobank, BioVU and Yale-Penn 3, resulting in a total n = 639063 (ncases= 20686; neffective= 77,026) across strains. Cases of OUD were defined as having a lifelong diagnosis of OUD, and controls such as no person known to meet the criteria for OUD. We estimated SNP (h . heritability)2SNP ) and genetic links (pgg ).

Based on genetic association, we performed MTAG on OUD, alcohol use disorder (AUD), and cannabis use disorder (CanUD). A polygenic risk score (PRS) analysis was performed to compare OUD and OUD-MTAG PRS as predictors of OUD status in Yale-Penn 3.

The EUR meta-analysis identified three genome-wide associations (GWS; s ≤ 5 x 10−8) lead SNPs – one in foreign (rs11372849; s= 9.54 x 10−10) and two OPRM1variants (rs1799971, s= 4.92 x 10−09; rs79704991, s= 1.11 x 10−08; s2= 0.02). 1799971 Indian rupees (p = 4.91 x 10−08) and another OPRM1variant (rs9478500; s= 1.95 x 10−08; s2= 0.03) in a cross-breed meta-analysis. estimated h2SNPIt was 12.75%, with rgwith CanUD (pg= 0.82; s= 1.14 x 10−47) and AUD (pg= 0.77; s= 6.36 x 10−78).

OUD-MTAG resulted in GWAS NEquivalent= 128,748 and 18 independent GWS loci, some mapping of genes or gene regions that have been previously associated with psychiatric or addiction phenotypes.

The OUD-MTAG PRS represents 3.81% of the OUD variance (beta = 0.61; se = 0.066; s= 2.00 x 10−16) compared to 2.41% (beta = 0.45; se = 0.058; s= 2.90 x 10−13) Explained by OUD PRS. The current study identified different OUD correlations in OPRM1one variable with foreignand 18 GWS associations in the OUD-MTAG.

The genetic structure of OUD is likely to be influenced by both loci for OUD and loci shared across SUDs.