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lukejoconnor / LCV

Software implementing the Latent Causal Variable Model
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Inconsistent LCV results for the same pair of traits #10

Open ElizavetaElgaeva opened 4 years ago

ElizavetaElgaeva commented 4 years ago

Dear LCV developers,

We ran three LCV tests to study a relationship between two UKBB traits - varicose (VV, three sets of GWAS data, rg = 0.98 - 1.00) and ostearthritis (OA) - and obtained controversial GCP estimates (all of them statistically significant, but differ in sign and magnitude). Thus, in two analyses we observed GCP < -0.6, but the third GCP value was equal to 0.12 (please, see the full table with the results LCV_results for OA and VV.xlsx).

We expected to get concordant LCV results for all three analyses since we studied the same trait pair and used the data highly genetically correlated between datasets. What could be a reason for such contradicting results? How should they be interpreted?

Here https://drive.google.com/drive/folders/1_HWYDanaeZ1dT1xaPwZQDOYPk6GjFWdG?usp=sharing you could find processed data for VV and OA, munged using GenomicSEM R-package with maf.filter = 0.05 and HapMap 3 reference data for 1000 people.

The code for the LCV-analyses available via the link https://drive.google.com/drive/folders/1kdBebTmwguEnGD_JWAqb0e_EvLFLMEXI?usp=sharing.

Data description:

For VV, we tested GWAS summary statistics from 3 open UKBB-based resources with a strong genetic correlation between each other (rg = 0.98-1.00, LCV estimates). For OA, we used only one dataset.

Trait 1 – “varicose veins of lower extremities” (VV) • Resource 1 – Gene Atlas (trait: I83: VVs of lower extremities) • Resource 2 – The Neale Lab (trait: I83: VVs of lower extremities) • Resource 2 – PheWeb (PheWAS code 454.1: VVs of lower extremity)

Trait 2 – “osteoarthritis, localized, primary” (OA) • Resource – PheWeb (PheWAS code 740.11: Osteoarthrosis, localized, primary)

humanpaingeneticslab commented 2 years ago

Dear Elizaveta,

in LCV's "Supplementary Table 10: 52 GWAS datasets included in the analysis." they say "estimated genetic correlation ρ_g < 0.9 with other traits." Now I wonder why they choose that; could it be if the genetic correlation is too strong (as in your case) then assumptions about LCV are violated? Will read more...