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Before or after LD clumping for PRS calculation in GWAS

Hello I'm new to GWAS analysis and I have a one question about LD clumping step during PRS calculation with plink. If I understand correctyly, PRS score calculation steps can be summarized as shown below.

  1. association test (logistic regression for the binary phenotype)
  2. LD clumping , p-value threholding (avoiding overfitting)
  3. Calculating PRS by using SNPs from step 2 and betavalue from step 1

My question is, Is it wrong that LD clumping precede the association test? I think the SNPs in LD block might affect the beta values during association test quite strongly, so that i think the LD clumping should be conducted prior to the association test. Please let me know if there is any point that i misunderstood . Thank you

KJ

gwas
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written by K Lee • K Lee

1 answer

  1. Association testing are done on each SNP independently. So it would not affect the beta
  2. If you do prunning before association (you cannot do clumping without p-value), you will not capture the most associated SNPs with your trait of interest You can refer to the PGS tutorial paper: https://www.nature.com/articles/s41596-020-0353-1
• 0 views • link
written by Sam Sam
  1. I think i misunderstood logistic regression of association test. Now I understand.
  2. you're right. Thank you for your helpful reply sam!
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written by K Lee • K Lee

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