Genome-wide meta-analysis identifies genetic risk loci for mono- and polyneuropathies in 983 477 individuals, 2026, Broberg et al.

[SNT Gatchaman]

Genome-wide meta-analysis identifies genetic risk loci for mono- and polyneuropathies in 983 477 individuals

Spoiler: Authors

Broberg, Martin; Gen, Finn; Kalso, Eija; Ollila, Hanna M

Peripheral neuropathies are common neurological disorders affecting sensory, autonomic, and motor nerves, with an estimated prevalence exceeding 2% in the general population. Typical symptoms include numbness and distal limb muscle weakness, resulting from somatosensory nerve damage.

Here, we investigate the genetic architecture of mono- and polyneuropathies and their relationships with comorbid traits using data from FinnGen and the UK Biobank. Our genome-wide association study (GWAS) and meta-analysis identified 48 genome-wide significant (P < 5 × 10−8 ) independent loci and 66 fine-mapped credible sets.

These included associations with genes involved in neurotransmitter signaling (HTR3A), immune function (HLA-DQB1, BCL11A), extracellular matrix remodeling (COL11A1, ADAMTS17, LOXL4), axon guidance and neural development (DCC, ETV1, NEGR1), and carpal tunnel syndrome (DIRC3). Public variant association data across cohorts, genetic correlation, and Mendelian randomization analyses supported shared genetic links of neuropathies with sleep problems, chronic pain, and psychiatric disorders.

Together, our results highlight a strong polygenic basis for neuropathies and further confirm their genetic comorbid relationships with sleep, pain, psychiatric, and autoimmune traits.

Web | DOI | PDF | Human Molecular Genetics | Open Access

 

[V.R.T.]

HLA-DQB1

Interesting...

Edit: and DCC

 

[Utsikt]

Interesting...

Edit: and DCC

NEGR1 is also familiar.

 

[SNT Gatchaman]

Also DCC.

Identification of Novel Reproducible Combinatorial Genetic Risk Factors for Myalgic Encephalomyelitis in the DecodeME Patient Cohort and Commonalities with Long COVID (2025)

The genetic architecture of fibromyalgia across 2.5 million individuals (2025)

Neurodevelopment Genes Encoding Olduvai Domains Link Myalgic Encephalomyelitis to Neuropsychiatric Disorders (2025)

 

[forestglip]

Also DCC.

Identification of Novel Reproducible Combinatorial Genetic Risk Factors for Myalgic Encephalomyelitis in the DecodeME Patient Cohort and Commonalities with Long COVID (2025)

The genetic architecture of fibromyalgia across 2.5 million individuals (2025)

Neurodevelopment Genes Encoding Olduvai Domains Link Myalgic Encephalomyelitis to Neuropsychiatric Disorders (2025)

Also DecodeME. While it didn't quite reach the genome-wide significance threshold, it had a p-value of 2.48x10-7, so there's still a good chance it's a real finding. The locus can be seen in this post.

 

[forestglip]

The results from the HLA allele finemapping in FinnGen demonstrated nine HLA alleles significantly associated with neuropathies, of which the top five all are part of a well-established 8.1 ancestral haplotype [25] (Table 5).

Table 5:

It looks like alleles of this haplotype increase risk of neuropathies.

This is the same haplotype that looked to be protective against ME/CFS in Lande 2020, with supporting evidence from other studies:

There were two alleles with a negative association with ME/CFS, suggesting a potential protection, namely B*08:01 (OR = 0.7 [95% CI 0.6–0.9], pnc = 0.01, pc = n.s.) and [...]

The most frequent B*08:01 haplotype in Norway is the highly conserved so-called autoimmune and ancestral AH8.1 haplotype31 (C*07:01-B*08:01-DRB1*03:01-DQB1*02:01). This haplotype had reduced estimated frequency in the patient group compared to the control group (8.2% vs. 10.3%, OR = 0.8, pnc = 0.06), albeit not significantly.

In the existing literature on HLA and CFS, HLA-DRB1 is the locus most frequently studied. In four out of five studies, the frequency of DR3/DRB1*03 was lower in the patient group23,24,25,28, while in the fifth study the frequency was similar in both groups22. Hence, this haplotype seems truly less prevalent among ME/CFS patients.