Perhaps it's just that DecodeME on its own didn't have the precision to pinpoint BTN2A1, it's only with the DecodeME PheWAS of rare variants that it became a likely candidate. He talked about BTN2A1 during the presentation.
The meta-analysis only has three significant hits left, but includes one on chromosome 2 that we haven't discussed much because it only reached 10^-6 levels in DecodeME.
Potential genes are:
UGP2: converts glucose into UDP-glucose. The short form is primarily located in the brain.
VPS54...
He also refers to Paolo Maccalini's meta-analysis of DecodeME with results from other genetic databases. Not sure if we discussed this before. Looks like impressive work from Paolo.
https://github.com/paolomaccallini-hub/MetaME
If we focus on the ME/CFS category that had the clearest result: 8 out of 2547 (0.31%) had one of the mutations that disrupted BTN2A1.
But this was significantly more than the 50/121,923 (0.04%) in the control group.
This page shows the DNA mutations...
There are multiple ways to identify ME/CFS patients in the UK Biobank, as explained in this paper:
Defining a High-Quality Myalgic Encephalomyelitis/Chronic Fatigue Syndrome cohort in UK Biobank - PMC
Looks like there was also an increased odds ratio for BTN2A1 in the G93.3 ICD diagnosis...
The methods of the Astrazeneca analysis are explained in this 2021 paper:
Wang et al. 2021. Rare variant contribution to human disease in 281,104 UK Biobank exomes | Nature
Chris Ponting mentioned this in this thread:
https://www.s4me.info/threads/genetics-chromosome-6-btn2a2-and-btn3a3-btn2a1.45503/post-689176
The result can be viewed here...
What I don't quite get:
ME/CFS symptoms suggest a disease of T-cell activation
BTN2A1 is involved in activating the T-cell
ME/CFS patients are more likely to have defective BTN2A1
So that doesn't fit with T-cells being overactive after all?
Rather it suggests that at certain times the T-cells...
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