SAIGE Step 2 Error
I am trying to run an association test across chromosome 11 using SAIGE. I managed to use the step 1 tool (SAIGE GWAS GRM) without error, but am getting this error on part two (SAIGE GWAS - Single Variant Association Tests):
‘LOCO is TRUE but the null model file .rda does not contain LOCO results. In order to apply Leave-one-chromosome-out, please run Step 1 using LOCO. Otherwise, please set LOCO=FALSE in this step (Step 2).’
I can't find anything about setting the LOCO command to true/false when setting up my analysis with the tool. How can I fix this?
Thanks!
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1 comment
My assistant said…
This is a classic SAIGE “you asked for LOCO but didn’t bake LOCO into the cake” situation 🍰🧬 You ran Step 1 (null model / GRM) without LOCO, but Step 2 is trying to use LOCO. Step 2 cannot magically invent chromosome-specific null models. It only consumes what Step 1 produced. Let’s decode and fix it cleanly. --- 🧠 What’s Happening In SAIGE: Step 1 builds the null model (.rda) Step 2 runs association tests If Step 2 is set to: LOCO=TRUE then the .rda file must contain LOCO results generated in Step 1. Yours does not. Hence the error: > LOCO is TRUE but the null model file .rda does not contain LOCO results --- ✅ Two Ways to Fix It 🔹 Option 1 — Easiest: Turn LOCO OFF in Step 2 If you don’t specifically need LOCO: In the Step 2 tool settings: Find the parameter called LOCO Set it to: FALSE Re-run Step 2. Done. --- 🔹 Option 2 — Proper GWAS Practice: Re-run Step 1 with LOCO=TRUE If you do want LOCO (recommended for chromosome-wide tests): Re-run Step 1 with: LOCO=TRUE This will: Generate chromosome-specific null models Store LOCO results inside the .rda Allow Step 2 to run per chromosome correctly Then re-run Step 2 with: LOCO=TRUE Now they match. Harmony restored. --- 🧬 Should You Use LOCO? For chromosome-wide GWAS (like your chr11 test): Yes — LOCO is generally recommended. Why? Because when testing variants on chromosome 11: You don’t want the GRM built from chromosome 11 influencing its own test statistics. LOCO removes that chromosome from the random effects model. Think of it as temporarily excusing chromosome 11 from jury duty while it’s on trial ⚖️ --- 🔍 Why You Couldn't Find the Setting On RAP apps, LOCO is usually: A boolean toggle Or buried under “advanced options” Sometimes defaulted differently between Step 1 and Step 2 The key rule: > Step 1 LOCO setting must match Step 2 LOCO setting. Always. --- 🚀 Recommended Action For You Since you're running chromosome 11: I recommend: 1. Re-run Step 1 with LOCO=TRUE 2. Then re-run Step 2 with LOCO=TRUE 3. Run per chromosome as intended That’s the statistically clean approach. --- If you'd like, tell me: Are you running this through RAP app? Swiss Army Knife? Command line? WDL? I’ll give you the exact parameter location for your setup.
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