Question

Deleterious or Protective? --> CADD score >20 but Odds ratio <1

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2.9 years ago

Shab86 ▴ 310

So, I have a variant that has a CADD PHRED score of >20 but the OR is < 1. So, I am not sure whether this is a deleterious or protective variant? Any ideas on how to interpret this?

Thanks, Sabeer

variant deleteriousness genomics • 1.2k views

ADD COMMENT • link updated 2.9 years ago by Kevin Blighe 87k • written 2.9 years ago by Shab86 ▴ 310

score 2 · Accepted Answer · 2021-05-19

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2.9 years ago

Kevin Blighe 87k

Hi, its OR is < 1 from which study design? It may be better to think of CADD scores as measures of 'functionality', and not necessarily pathogenicity. So, a variant that introduces a functional change can be either advantageous or not. Even a deleterious variant can be advantageous.

ADD COMMENT • link 2.9 years ago by Kevin Blighe 87k

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Thanks Kevin for your reply! Its from a case-control design study (200k+ individuals), and that missense variant is genome-wide significant.

ADD REPLY • link 2.9 years ago by Shab86 ▴ 310

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Cool, it would be interesting if you could share the exact variant in question (?). Either way, I think that it is valid for a CADD score to be high for a protective variant.

ADD REPLY • link 2.9 years ago by Kevin Blighe 87k