I have been working on a prototype genetics app based on the hypothesis that phospholipase A2 (PLA2) activation may be increased in at least some people with ME/CFS.
It is not intended to diagnose ME/CFS, and I don’t want to present it as clinically validated. It looks through a person’s genetic data for variants in pathways that could plausibly contribute to increased PLA2 activation. I worked on making the app several months ago, but then paused work on it because I was unsure how accurate the variant scoring would be, and I also became busy with other things. I am now considering posting it online as a work-in-progress, to gain feedback.
The app currently works by grouping variants into pathway categories rather than trying to identify a single “ME/CFS gene”. For example, it looks at possible genetic contributors to:
* immune/cytokine-driven PLA2 activation
* oxidised LDL or lipoprotein-related PLA2 activation
* histamine/mast-cell signalling that could feed into cPLA2 activation
* phosphatidylcholine synthesis and phospholipid buffering
* arachidonic acid handling and eicosanoid pathways
My concern is that although many of the pathways are biologically plausible, the evidence for individual SNPs is variable. Some variants have reasonably clear functional or association data, while others are more speculative or context-dependent. I therefore think it would be much safer and more useful to publish it openly as a hypothesis-generating tool and ask for feedback, rather than treating the output as any kind of medical or diagnostic result.
My aim is not to claim that PLA2 activation explains all ME/CFS, but to explore whether a subgroup of patients might show genetic patterns that make excessive phospholipid hydrolysis more likely.
I think there could be subsets- one subset of people could have increased PLA2 activation due to increased oxidation of LDL, and others may have increased PLA2 activation due to immune pathways, some could be a mixture of both.
It is not intended to diagnose ME/CFS, and I don’t want to present it as clinically validated. It looks through a person’s genetic data for variants in pathways that could plausibly contribute to increased PLA2 activation. I worked on making the app several months ago, but then paused work on it because I was unsure how accurate the variant scoring would be, and I also became busy with other things. I am now considering posting it online as a work-in-progress, to gain feedback.
The app currently works by grouping variants into pathway categories rather than trying to identify a single “ME/CFS gene”. For example, it looks at possible genetic contributors to:
* immune/cytokine-driven PLA2 activation
* oxidised LDL or lipoprotein-related PLA2 activation
* histamine/mast-cell signalling that could feed into cPLA2 activation
* phosphatidylcholine synthesis and phospholipid buffering
* arachidonic acid handling and eicosanoid pathways
My concern is that although many of the pathways are biologically plausible, the evidence for individual SNPs is variable. Some variants have reasonably clear functional or association data, while others are more speculative or context-dependent. I therefore think it would be much safer and more useful to publish it openly as a hypothesis-generating tool and ask for feedback, rather than treating the output as any kind of medical or diagnostic result.
My aim is not to claim that PLA2 activation explains all ME/CFS, but to explore whether a subgroup of patients might show genetic patterns that make excessive phospholipid hydrolysis more likely.
I think there could be subsets- one subset of people could have increased PLA2 activation due to increased oxidation of LDL, and others may have increased PLA2 activation due to immune pathways, some could be a mixture of both.
