Is associated snp authenticated by mtag valid when they are in HLA locus?

[Davidseye]

I am interested in IBD and another inflammatory disease(not typically immune-associated but contains a subclass which is auto-immune ), MTAG founds pleiotropy locus all in hla locus. The pvalue of all the snps authenticated in IBD are <10^-8, but in anpther disease ,they are usually 10^-4 .Should I reserve them? Actually, I dont want to give them up, however, most of study even those study IBD excludes HLA locus.

[paturley]

It's hard for me to make a suggestion here without disease-specific context. MTAG requires that the genetic correlation between the sets of traits is roughly constant across the whole genome. A way this could be violated is if there are regions of the genome that are important for one trait and not for others. In such a case, you may see inflated test statistics in the regions that are causal from the secondary trait but not for the focal trait. So the validity of the MTAG results depends a bit on whether you believe MTAG's assumptions.

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On Sun, Dec 1, 2024 at 7:00 AM Davidseye ***@***.***> wrote: I am interested in IBD and another inflammatory disease(not typically immune-associated but contains a subclass which is auto-immune ), MTAG founds pleiotropy locus all in hla locus. The pvalue of all the snps authenticated in IBD are <10^-8, but in anpther disease ,they are usually 10^-4 .Should I reserve them? Actually, I dont want to give them up, however, most of study even those study IBD excludes HLA locus. — Reply to this email directly, view it on GitHub <#224>, or unsubscribe <https://github.com/notifications/unsubscribe-auth/AFBUB5LY6QAXGTEVUVHOT2D2DL26RAVCNFSM6AAAAABSZTG4DWVHI2DSMVQWIX3LMV43ASLTON2WKOZSG4YDSMBZG4ZTMNI> . You are receiving this because you are subscribed to this thread.Message ID: ***@***.***>

[Davidseye]

Thanks for your reply! The issue I'm more concerned about is the mhc rigeon. Will the&nbsp; high LD influence the result of MTAG?

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---Original--- From: ***@***.***&gt; Date: Tue, Dec 3, 2024 23:30 PM To: ***@***.***&gt;; Cc: ***@***.******@***.***&gt;; Subject: Re: [JonJala/mtag] Is associated snp authenticated by mtag valid whenthey are in HLA locus? (Issue #224) It's hard for me to make a suggestion here without disease-specific context. MTAG requires that the genetic correlation between the sets of traits is roughly constant across the whole genome. A way this could be violated is if there are regions of the genome that are important for one trait and not for others. In such a case, you may see inflated test statistics in the regions that are causal from the secondary trait but not for the focal trait. So the validity of the MTAG results depends a bit on whether you believe MTAG's assumptions. On Sun, Dec 1, 2024 at 7:00 AM Davidseye ***@***.***&gt; wrote: &gt; I am interested in IBD and another inflammatory disease(not typically &gt; immune-associated but contains a subclass which is auto-immune ), MTAG &gt; founds pleiotropy locus all in hla locus. The pvalue of all the snps &gt; authenticated in IBD are <10^-8, but in anpther disease ,they are usually &gt; 10^-4 .Should I reserve them? Actually, I dont want to give them up, &gt; however, most of study even those study IBD excludes HLA locus. &gt; &gt; — &gt; Reply to this email directly, view it on GitHub &gt; <#224&gt;, or unsubscribe &gt; <https://github.com/notifications/unsubscribe-auth/AFBUB5LY6QAXGTEVUVHOT2D2DL26RAVCNFSM6AAAAABSZTG4DWVHI2DSMVQWIX3LMV43ASLTON2WKOZSG4YDSMBZG4ZTMNI&gt; &gt; . &gt; You are receiving this because you are subscribed to this thread.Message &gt; ID: ***@***.***&gt; &gt; — Reply to this email directly, view it on GitHub, or unsubscribe. You are receiving this because you authored the thread.Message ID: ***@***.***&gt;