A 2015 study of every major myositis subtype found that one extended immune haplotype, inherited as a block, accounts for essentially all of the identified genetic risk.
Myositis is a group of autoimmune muscle diseases in which the immune system attacks muscle tissue, causing weakness and, in some subtypes, a distinctive skin rash. The major subtypes — dermatomyositis, polymyositis, and juvenile dermatomyositis — differ somewhat in presentation and age of onset but share an underlying autoimmune mechanism.
Miller et al. 2015 ran a genome-wide association study across the major myositis phenotypes: 1,710 cases in total — 705 adult dermatomyositis, 473 juvenile dermatomyositis, 532 polymyositis, and 202 patients across those subtypes who also carried anti-Jo-1 autoantibodies — compared against 4,724 controls. Every genome-wide-significant signal found, whether the phenotypes were analysed together or separately, fell within the MHC region on chromosome 6, the genomic stretch that shapes how the immune system recognizes self versus foreign tissue.
Imputation and regression analysis went further: alleles making up the HLA 8.1 ancestral haplotype (AH8.1) — a large, extended block of the MHC region that tends to be inherited together as a unit rather than shuffled apart by recombination — accounted for essentially all of the genetic risk identified, across geographically diverse study populations. Some fine structure emerged within that broad finding: HLA-DRB1*03:01 showed a slightly stronger association with dermatomyositis specifically, and HLA-B*08:01 with polymyositis and anti-Jo-1-positive myositis — but the paper found that multiple AH8.1 alleles together were needed for the full risk effect, not any single one alone.
This page's 8 variants — in or near HLA-DQB1, PMSP, HCP5 (twice), HCG26 (twice), MICB, and DDX39B — all sit within or immediately beside the MHC region the AH8.1 haplotype spans, consistent with the paper's central finding that this single extended haplotype, not scattered independent genes, drives myositis risk.
Positions joined since this page was written
What this is The text above discusses the variants this page was written around. Since then the catalogue has joined 1 more position to it, by shared trait or shared paper. They are listed here by the paper each came from; the text does not describe them, and each variant page carries that study's own record.
Sakaue S et al. 2021, Nature genetics rs577482058 (LRP5) — PMID:34594039
Myositis is diagnosed through muscle strength testing, blood markers of muscle damage, autoantibody testing, and often a muscle biopsy — not through any variant on this page. The genetic risk described here is a population-level finding about susceptibility, not a diagnostic or predictive test for an individual.
Because AH8.1 is inherited as a large block rather than as independent alleles, no single variant on this page can be interpreted in isolation from the others — the paper's own finding is that the haplotype's risk comes from the combination, not any one part.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Myositis comes down to these specific, well-studied positions — not a diagnosis.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 9 of 10 linked studies with a resolved discovery ancestry.
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Myositis. MyGeneLog™. https://www.mygenelog.com/conditions/myositis
Myositis is a group of autoimmune muscle diseases — including dermatomyositis, polymyositis, and juvenile dermatomyositis — in which the immune system attacks muscle tissue, causing weakness and sometimes a distinctive skin rash.
Studying 1,710 cases across all major myositis subtypes against 4,724 controls, it found that one extended immune haplotype, the HLA 8.1 ancestral haplotype, accounted for essentially all of the identified genetic risk.
No. Myositis is diagnosed through muscle strength testing, blood markers, autoantibody testing, and often a muscle biopsy — not through genotype.
The HLA 8.1 haplotype spans the MHC region that shapes immune recognition broadly, which may explain why it contributes risk across dermatomyositis, polymyositis, and related autoimmune muscle diseases rather than just one specific subtype.
Free to reuse. This page's text is original writing from freely-available research, licensed CC BY 4.0 — reuse it, including commercially, with attribution to MyGeneLog™. It's general research-derived information, not medical advice or a diagnosis — see Terms of Use.