Related Experiment Video

Updated: Jan 21, 2026

Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets
11:19

Genome-wide Analysis using ChIP to Identify Isoform-specific Gene Targets

Published on: July 7, 2010

15.0K

Genome-wide scan identifies opioid overdose risk locus close to MCOLN1

Zhongshan Cheng1, Bao-Zhu Yang1, Hang Zhou1

  • 1Division of Human Genetics, Department of Psychiatry, Yale University School of Medicine and VA CT Healthcare Center, New Haven, CT, USA.

Addiction Biology
|July 31, 2019
PubMed

Insights

Researchers identified potential genetic risk factors for opioid overdose severity. Mucolipin 1 (MCOLN1) gene variants were associated with overdose risk in African Americans, suggesting MCOLN1 as a potential target for preventing opioid overdoses.

Area of Science:

  • Genetics and Genomics
  • Pharmacology
  • Public Health

Background:

  • The United States faces a severe opioid overdose crisis.
  • Genetic predispositions may influence opioid overdose (OpOD) severity.
  • Understanding genetic risk is crucial for developing targeted interventions.

Purpose of the Study:

  • To conduct a genome-wide association study (GWAS) to identify genetic variants associated with opioid overdose severity.
  • To investigate potential genetic risk factors in European American (EA) and African American (AA) populations.
  • To explore the functional role of identified genetic loci in opioid overdose.

Main Methods:

  • Genome-wide association study (GWAS) on 3,477 opioid-exposed individuals (2,032 EA, 1,445 AA), including 1,019 with opioid overdoses.
  • Severity scoring based on overdose status and medical treatment frequency.
  • Post-GWAS analysis including network analysis (gene coexpression) and drug repositioning analysis (Connectivity Map database).

Main Results:

  • Two genome-wide significant (GWS) signals were identified in African Americans near MCOLN1/PNPLA6 (rs115208233, rs116181528, rs114077267) and DDX18 (rs369098800); no GWS signals in European Americans.
  • Network analysis revealed MCOLN1-associated genes enriched in calcium and cation channel activities relevant to OpOD.
  • Drug repositioning analysis suggested MCOLN1 overexpression profiles align with opioid agonist drug effects, identifying potential therapeutic avenues.

Conclusions:

  • Mucolipin 1 (MCOLN1) may be a risk gene for opioid overdose severity, particularly in African American populations.
  • MCOLN1's role in calcium and cation channel activity warrants further investigation for its contribution to OpOD.
  • Findings could guide the identification of novel drug targets for preventing opioid overdose, though replication studies are necessary.
Keywords:
African AmericansEuropean AmericansMCOLN1genome-wide associationopioid overdose

More Related Videos

Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells14:26

Genome-wide Purification of Extrachromosomal Circular DNA from Eukaryotic Cells

Published on: April 4, 2016

25.9K
RNA Next-Generation Sequencing and a Bioinformatics Pipeline to Identify Expressed LINE-1s at the Locus-Specific Level11:04

RNA Next-Generation Sequencing and a Bioinformatics Pipeline to Identify Expressed LINE-1s at the Locus-Specific Level

Published on: May 19, 2019

10.4K

Related Concept Videos

Genome-wide Association Studies-GWAS01:11

Genome-wide Association Studies-GWAS

Genome-wide association studies or GWAS are used to identify whether common SNPs are associated with certain diseases. Suppose specific SNPs are more frequently observed in individuals with a particular disease than those without the disease. In that case, those SNPs are said to be associated with the disease. Chi-square analysis is performed to check the probability of the allele likely to be associated with the disease.
GWAS does not require the identification of the target gene involved in...
15.4K
Opioid Analgesics: Synthetic and Semisynthetic Opioids01:15

Opioid Analgesics: Synthetic and Semisynthetic Opioids

Synthetic and semisynthetic opioids are pivotal in pain management and tackling opioid addiction. Semisynthetic opioids, including morphinans (morphine derivatives), oxycodone, oxymorphone, hydrocodone, and hydromorphone, have improved pharmacokinetic profiles compared to morphine. Additionally, heroin and 6-MAM (6-Monoacetylmorphine) show better CNS penetration than morphine due to heightened lipid solubility. Hydromorphone, a potent opioid, undergoes hepatic metabolism to form the active...
952
Opioid Receptors: Overview01:22

Opioid Receptors: Overview

Opioid receptors, including the mu (μ, MOR), delta (δ, DOR), and kappa (κ, KOR) types, belong to the rhodopsin family of G protein-coupled receptors. These receptors are located throughout the central and peripheral nervous systems and in non-neuronal tissues such as macrophages and astrocytes. Opioid receptor ligands can be categorized into agonists or antagonists. Highly selective agonists include [d-Ala2, MePhe4, Gly(ol)5]-enkephalin or DAMGO for MOR, [D-Pen2,...
4.1K
Genomics02:02

Genomics

Genomics is the science of genomes: it is the study of all the genetic material of an organism. In humans, the genome consists of information carried in 23 pairs of chromosomes in the nucleus, as well as mitochondrial DNA. In genomics, both coding and non-coding DNA is sequenced and analyzed. Genomics allows a better understanding of all living things, their evolution, and their diversity. It has a myriad of uses: for example, to build phylogenetic trees, to improve productivity and...
39.8K
Locus of Control01:26

Locus of Control

Locus of control describes how individuals perceive the causes of events in their lives, influencing motivation and well-being. Introduced by Julian Rotter in 1954, it is categorized into internal and external locus of control.Internal Locus of ControlIndividuals with an internal locus of control believe their actions determine outcomes, fostering responsibility, self-efficacy, and motivation. For example, an employee may attribute career success to hard work. Research links this mindset to...
209
Root-Locus Method01:19

Root-Locus Method

A cruise control system in a car is designed to maintain a specified speed automatically by adjusting the gas pedal. The system continuously measures the vehicle's speed and makes fine adjustments to the pedal to achieve this goal. The root locus method is particularly useful for understanding how the cruise control system's behavior changes under varying conditions, such as when the car goes uphill, downhill, or faces strong wind resistance.
This system can be represented by a block...
483