Is MTAG sensitive to sex imbalance?

[NephronTurner]

Hello there,

Thank you for your excellent resource. I wondered if I might ask about whether MTAG is sensitive to sex imbalance. I cannot think why this would be, but wanted to make sure.

I have performed MTAG on GWAS of four correlated traits which were all carried out in the same cohort which is 66% women. Across all four traits there is one borderline GWAS-significant signal near the start of chromosome X. However, the MTAG results show many strongly-associated loci across chromosome X, which come out as conditionally independent on further analysis. One spike becomes our third-strongest signal.

I would just like to check that we are not obtaining spurious associations due to our sex imbalance. For the avoidance of doubt, each individual GWAS was of course adjusted for sex.

Many thanks for your time.

Michael

[paturley]

I can't think of why a sex imbalance would create problems for MTAG as long as the assumptions of MTAG are met. Generally, MTAG inherits the biases of the input GWAS though, so as long as the inputs aren't biased, you should be fine.

On Thu, Nov 24, 2022, 7:32 AM Mike Turner @.***> wrote:

Hello there,

Thank you for your excellent resource. I wondered if I might ask about whether MTAG is sensitive to sex imbalance. I cannot think why this would be, but wanted to make sure.

I have performed MTAG on GWAS of four correlated traits which were all carried out in the same cohort which is 66% women. Across all four traits there is one borderline GWAS-significant signal near the start of chromosome X. However, the MTAG results show many strongly-associated loci across chromosome X, which come out as conditionally independent on further analysis. One spike becomes our third-strongest signal.

I would just like to check that we are not obtaining spurious associations due to our sex imbalance. For the avoidance of doubt, each individual GWAS was of course adjusted for sex.

Many thanks for your time.

Michael

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