is a1 reference or effect?

[mgarrett1020]

Hi--
I read in the wiki that a1 is the effect allele:
a1 is considered to be the effect allele, which should also be reflected in the signs of the Z-scores.

The log file however says that a1 is the reference allele:
Interpreting column names as follows:
snpid: Variant ID (e.g., rs number)
n: Sample size
a1: a1, interpreted as ref allele for signed sumstat.
pval: p-Value
a2: a2, interpreted as non-ref allele for signed sumstat.
z: Directional summary statistic as specified by --signed-sumstats.
se: Standard errors of BETA coefficients

Can you please confirm which allele is the tested/effect allele?

Thanks,
Melanie

[paturley]

Hi Melanie, I believe that a1 is the effect allele. That is, the beta is the estimated effect of increasing the a1 allele count by one. When we wrote the MTAG paper, there was some ambiguity in the literature of whether "reference allele" referred to the effect allele or not, so that's caused a lot of confusion. We should've used "effect allele" the whole time. Best, Patrick

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On Wed, Dec 10, 2025 at 10:33 AM mgarrett1020 ***@***.***> wrote: *mgarrett1020* created an issue (JonJala/mtag#247) <#247> Hi-- I read in the wiki that a1 is the effect allele: a1 is considered to be the effect allele, which should also be reflected in the signs of the Z-scores. The log file however says that a1 is the reference allele: Interpreting column names as follows: snpid: Variant ID (e.g., rs number) n: Sample size a1: a1, interpreted as ref allele for signed sumstat. pval: p-Value a2: a2, interpreted as non-ref allele for signed sumstat. z: Directional summary statistic as specified by --signed-sumstats. se: Standard errors of BETA coefficients Can you please confirm which allele is the tested/effect allele? Thanks, Melanie — Reply to this email directly, view it on GitHub <#247>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/AFBUB5KKHPRR6EHQMB5ZJX34BA4MBAVCNFSM6AAAAACOUERT2SVHI2DSMVQWIX3LMV43ASLTON2WKOZTG4YTKNZRGMZDCNI> . You are receiving this because you are subscribed to this thread.Message ID: ***@***.***>