I searched the keyword ALDH1A2 and arrived at this web link for the ALDH1A2 gene: Open Targets Genetics.
I downloaded the CSV file on ALDH1A2 variants correlated with different phenotypes and measurements and then extracted the variants associated with kidney function- or damage-related biomarkers.
I next tried to find details of the ALDH1A2 variants in the above table.
Surprisingly, I found 7 variant IDs associated with Cystatin-C, Scr and eGFR are missense or intron variants of CGNL1 and they do not seem to be related to ALDH1A2.
Index Variant RSID
rs1620402
rs16977594
rs16977594
rs1994887
rs1623697
rs1994887
rs57995724
The remaining five associated with serum albumin levels, TNF and KIM-1 are all ALDH1A2 intron variants.
Index Variant RSID
rs1532085
rs7182229
rs261334
rs1601934
rs1601934
Could you please kindly advise why CGNL1 Variants become hits when searching for ALDH1A2 variants?
In addition, could you please kindly advise on the best way to interpret the Beta value? For example, in studies on gene variant associations with TNF levels, KIM-1 levels and serum albumin levels, if the Beta values are -0.05, -0.074 and 0.0155, respectively, does it mean that the corresponding variants are associated with lower TNF levels, lower KIM-1 and higher serum albumin levels, respectively?
Welcome to Open Targets genetics! Thank you for your questions!
For the ALDH1A2 gene page, it is displaying studies which contain association loci that show evidence of interacting with ALDH1A2. From this table, the list of variants pasted has weak evidence towards interacting with ALDH1A2 (far away in genomic distance, no colocalisation, etc.). Hence the gene prioritisation pipelines are highlighting CGNL1 instead.
If you clicked directly on the link to the variants, you will arrive at the “variant page”, under which the gene assignment score shown is the study-agnostic V2G score, this is derived differently from the L2G score. If instead you click on the “gene prioritisation” button, it will redirect you to the full L2G summary for your variant in the study you are interested in.
Regarding your query about the interpretation of the beta value in the association table, they are the beta values from the study. Therefore in your example of TNF associations, the variants would be associated with the levels of TNF. The L2G score does not directly demonstrate directionality of effect for KIM-1 levels on TNF levels, although the colocalisation results can provide some insight into this, as the QTL beta values are displayed in the colocalisation tables.
Many thanks for replying to my enquiry. To further understand your message, is it possible to have a Zoom, Teams or WeChat chat online? I am based in London, the UK.