Migraine and major depressive disorder (MDD) are common brain disorders that frequently co-occur. Despite epidemiological evidence that migraine and MDD share a genetic basis, their overlap at the molecular genetic level has not been thoroughly investigated. Using single-nucleotide polymorphism (SNP) and gene-based analysis of genome-wide association study (GWAS) genotype data, we found significant genetic overlap across the two disorders. LD Score regression revealed a significant SNP-based heritability for both migraine (h = 12%) and MDD (h = 19%), and a significant cross-disorder genetic correlation (r = 0.25; P = 0.04). Meta-analysis of results for 8,045,569 SNPs from a migraine GWAS (comprising 30,465 migraine cases and 143,147 control samples) and the top 10,000 SNPs from a MDD GWAS (comprising 75,607 MDD cases and 231,747 healthy controls), implicated three SNPs (rs146377178, rs672931, and rs11858956) with novel genome-wide significant association (P ≤ 5 × 10) to migraine and MDD. Moreover, gene-based association analyses revealed significant enrichment of genes nominally associated (P ≤ 0.05) with both migraine and MDD (P = 0.001). Combining results across migraine and MDD, two genes, ANKDD1B and KCNK5, produced Fisher's combined gene-based P values that surpassed the genome-wide significance threshold (P ≤ 3.6 × 10). Pathway analysis of genes with P ≤ 1 × 10 suggested several pathways, foremost neural-related pathways of signalling and ion channel regulation, to be involved in migraine and MDD aetiology. In conclusion, our study provides strong molecular genetic support for shared genetically determined biological mechanisms underlying migraine and MDD.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6057914 | PMC |
| http://dx.doi.org/10.1038/s41431-018-0150-2 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Bidirectional two-sample Mendelian randomization analysis identifies causal associations between migraine and five psychiatric disorders.
Front Neurol
August 2024
Key Specialty of Clinical Pharmacy, The First Affiliated Hospital of Guangdong Pharmaceutical University, Guangzhou, China.
Background: The question of whether a correlation exists between migraine and five psychiatric disorders, including posttraumatic stress disorder (PTSD), major depressive disorder (MDD), anorexia nervosa (AN), bipolar disorder (BIP), and schizophrenia (SCZ), remains a matter of controversy. Hence, this research aims to investigate whether there is a possible association between migraine and five psychiatric disorders.
Methods: We performed a bidirectional 2-sample Mendelian randomization (MR) analysis to assess the causality between migraine and five psychiatric disorders.
Understanding the kynurenine pathway: A narrative review on its impact across chronic pain conditions.
Mol Pain
August 2024
Trauma and Surgery Research Center, AJA University of Medical Sciences, Tehran, Iran.
Article Synopsis
- * The kynurenine pathway is crucial for breaking down tryptophan and impacts neurotransmitter regulation, immune responses, and inflammation, making it relevant to various chronic pain conditions and MDD.
- * Research indicates that specific metabolites from this pathway can either protect or damage the nervous system, and targeting this pathway may lead to new, non-opioid pain management strategies.
Associations of long-term exposure to low-level PM and brain disorders in 260,922 middle-aged and older adults.
Chemosphere
August 2024
School of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, 200025, China. Electronic address:
Long-term exposure to high-level ambient PM was associated with increased risks of brain disorders, while the associations remain uncertain when the exposure is lower than current air quality standards in numerous countries. This study aimed to assess the effects of PM exposure on the brain system in the population with annual mean concentrations ≤15 μg/m. We analyzed data from 260,922 participants without preexisting brain diseases at baseline in the UK Biobank.
View Article and Find Full Text PDFEffects of Chronic Pain Diagnoses on the Antidepressant Efficacy of Transcranial Magnetic Stimulation.
Psychosom Med
July 2024
From the VA San Diego Healthcare System (Afshar, Fishbein, Martinez, Chu, Shenasa, Ramanathan, Herbert); Department of Psychiatry (Afshar, Fishbein, Shenasa, Ramanathan, Herbert), University of California; and VA Center of Excellence for Stress and Mental Health (Fishbein, Chu, Ramanathan, Herbert), San Diego, California.
Objective: Major depressive disorder (MDD) and chronic pain are highly comorbid and bidirectionally related. Repetitive transcranial magnetic stimulation (rTMS) over the dorsolateral prefrontal cortex is effective in treating MDD, but additional research is needed to determine if chronic pain interferes with rTMS for MDD.
Methods: Participants were 124 veterans ( Mage = 49.
Migraine and major depression: localizing shared genetic susceptibility in different cell types of the nervous systems.
Front Neurol
November 2023
Department of Surgery, College of Medicine, University of Florida, Gainesville, FL, United States.
Background: There is a bidirectional relationship between migraine and major depression disorder (MDD). They likely share important risk genes associated with different cell types in the central nervous system (CNS) and peripheral nervous system (PNS). Profiling the expression of these genes in specific cell types is critical in understanding the pathophysiology of the relationship between migraine and MDD.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!