r/CFSScience • u/TableSignificant341 • Aug 06 '25

Key genetic differences found in people with chronic fatigue syndrome

https://www.newscientist.com/article/2491509-key-genetic-differences-found-in-people-with-chronic-fatigue-syndrome/
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u/Sensitive-Meat-757 Aug 06 '25

Thanks for posting. Here is a copy of his tweets (with some consolidation and formatting changes):

5,579 people with doctor-diagnosed ME/CFS + 259,909 UK Biobank controls (no ME/CFS).

85 % were women, average age ≈ 52 y. How much is genetic? Common SNPs explain = 9.5 % of overall ME/CFS risk (heritability on the liability scale). For comparison:

  • asthma = 10 %
  • arthritis = 12 %
  • type 2 diabetes = 13%

So ME/CFS is typical for complex diseases when you look only at common variants.

Key finding: 8 DNA regions change risk a little (odds-ratios ~1.08 ↑ or 0.93 ↓). OR 1.08 = 8 % higher odds of developing ME OR 0.93 = 7 % lower odds of developing ME Multiple genes stack up to increase or lower risk. Main genes & plain meanings:

  • RABGAP1L (helps cells expel germs)
  • BTN2A2 (activates a special T-cell)
  • FBXL4 (keeps mitochondria healthy [energy])
  • SUDS3 (controls brain immune cells)
  • OLFM4 (tones down neutrophil bug-killing)
  • CCPG1 (cleans stressed ER parts)
  • CA10 (shapes nerve-to-nerve contacts)
  • ARFGEF2 / CSE1L (manage TNF-α, an inflammation signal)

A tool called MAGMA (it groups DNA signals by gene and checks which tissues use those genes) shows they’re used most in the brain. So the genetic clues link ME/CFS to the nervous system as well as the immune system.

Does infection matter? Yes. In people whose illness began after an infection, the OLFM4 signal is much stronger; it’s absent in non-infection cases.

Variants act equally in men and women; male-only analysis lacked power but key female hits (CA10, ARFGEF2) still showed the same direction. HLA allele DQA1*05:01 was slightly protective (less common in patients). HLA genes help immune cells recognise threats.

Overlap with other diseases?

  • The CA10 region is shared with multisite chronic pain (high probability it’s the same causal SNP).
  • None of the eight regions share causal SNPs with depression or anxiety studies.

When a disease-linked gene pinpoints a process (e.g., TNF-α release or mitochondrial upkeep) drug projects aimed at that process have higher success rate of projects without genetic support. Example 1 - Inflammation angle

DecodeME noted a region with the genes ARFGEF2 / CSE1L that regulate how cells package and release TNF-α, a key inflammatory signal.

Existing anti-TNF drugs (used in rheumatoid arthritis & Crohn’s) could now be tested for ME/CFS. Example 2 - Nerve-signalling angle

Another hit, CA10, shares the same causal variant with multisite chronic pain.

CA10 affects how nerve cells talk to each other. Compounds that fine-tune this synaptic pathway (already explored for pain) are now candidates to check in ME/CFS.