Immune SNP cluster (IRF5 / STAT4 / TYK2) — Is this worth pushing harder on with my doctor? Hoping for expert insight

[Chromowitch]

Hi all—
I’m not a clinician or researcher but do come from a health care background, and have a long autoimmune history and have had to do a lot of digging on my own. I’ve been trying to understand whether what I’m seeing in my raw DNA data (analyzed via Promethease and SNPedia) is meaningful—or just noise and my understanding is this is the place and the people to ask.

Over the past decade, I’ve experienced a persistent collection of autoimmune-adjacent symptoms:

Fatigue, joint/muscle pain

Hematuria (on and off for years)

Cold extremities, photoflushing

Subclinical hypothyroidism and elevated TSH

Dry mouth and GI flares

Positive SS-B (La) antibody

ANA negative (repeat tests pending)


Lab work shows subtle but chronic signs of immune dysfunction. Despite this, I’ve remained “undiifferentiated” in the eyes of most doctors.


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What I found in my SNP data:

I’ve identified a cluster of variants that individually are associated with interferon signaling and B/T cell immune regulation:

IRF5: rs2004640 (T), rs10954213 (A), rs2280714 (T) — all risk alleles

STAT4: rs7574865 (T/T — homozygous risk)

TYK2: rs34536443 (C:G — heterozygous for P1104A)

Other relevant SNPs:

PTPN22: rs2476601 (G:A — heterozygous risk)

TNFAIP3: rs5029939

BANK1: rs10516487

Possible HLA-DRB1 tagging SNPs



These all show up repeatedly in studies of lupus, Sjögren’s, RA, and polyautoimmune/interferonopathies—but I haven’t found resources that explain whether the combination is meaningful, or just coincidental.


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What I’m hoping for:

A reality check from someone familiar with immune-genetic modeling or variant interpretation

Is this the kind of SNP profile that would justify advocating harder with a rheumatologist or immunologist?

Is this combination biologically relevant enough to suggest interferon dysregulation or polyautoimmunity—even if labs are borderline?


I’m not looking for diagnosis—just hoping for guidance from someone who works with immune SNPs and can say:

> “Yes, this is something real you should pursue.”
Or
“No, these don’t carry that kind of cumulative weight.”



Happy to provide anonymized data if helpful.
Thank you so much for your time—and for seeing people like me.


Chromowitch

[Tahir HB]

You should also share the data how have you excluded all these SNPs from being artifacts or noise? Your report should describe that, so if anyone wants to comment would have procedural details as well, such as sequenced on what? oxford minipore ? illuma? i mean you should describe something on method used for variant calling alos before you could ask for any assement on these polymorphs.

[Chromowitch]

You should also share the data how have you excluded all these SNPs from being artifacts or noise? Your report should describe that, so if anyone wants to comment would have procedural details as well, such as sequenced on what? oxford minipore ? illuma? i mean you should describe something on method used for variant calling alos before you could ask for any assement on these polymorphs.

Thanks for your response, Tahir. I appreciate the technical lens, but just to clarify—this wasn’t raw sequencing data or novel variant analysis. My SNPs were called via Ancestry genotyping, and interpreted using Promethease and SNPedia cross-references.
I’m not trying to validate novel findings or ask for functional assays—just hoping for a sanity check from someone familiar with immune SNP clustering: whether this specific set of variants (e.g., IRF5, TYK2, STAT4, BANK1, TNFAIP3) carries enough weight, cumulatively, to merit pushing harder for autoimmune workup—despite borderline labs.

I totally understand if that’s not your focus area, and I welcome any insight from others who work with consumer data in clinical-genetic advocacy contexts. Thanks again.