An autoimmune disease that can affect almost any organ, with strong genetic involvement and dozens of known loci that together still explain a small share of it. The variant here was found in Asian populations, which is less common than it should be in this field.
Systemic lupus erythematosus is an autoimmune disease in which the immune system produces antibodies against the body's own material, particularly the contents of cell nuclei. It can affect skin, joints, kidneys, blood, lungs and brain, in almost any combination, and it typically runs in flares and remissions. It is far more common in women, and it is more common and often more severe in people of African, Hispanic and Asian ancestry than in people of European descent.
Lupus has one of the clearer hereditary components among autoimmune diseases, and dozens of susceptibility loci have been found. Together they still account for a small proportion of its heritability — a sentence the field writes about itself, and one worth repeating rather than glossing.
rs7329174 is in ELF1 and was identified in a genome-wide association study in a Hong Kong Chinese cohort with replication in two further Asian populations — 3,164 patients and 4,482 matched controls in total, with an odds ratio of 1.26.
ELF1 belongs to the ETS family of transcription factors and is involved in T cell development and function, which is a reasonable place for a lupus gene to be. The same study found the gene uses three alternative first exons, expressed at similar levels in patients and controls, and could not tie the associated variant directly to a change in those transcript levels — so the mechanism was left open rather than asserted.
Most genetic studies of most diseases have been done in people of European descent, and lupus is a disease where that is a particular problem, because it is more common in the populations studied least. A finding established in Chinese, and replicated in two other Asian populations, is exactly the kind of evidence the field needs more of.
It cannot diagnose lupus, predict it, or say how severe it will be. Diagnosis is clinical and serological — the pattern of organ involvement, antinuclear antibodies and more specific ones such as anti-dsDNA and anti-Sm, complement levels, urine testing for kidney involvement. Treatment decisions follow the disease's behaviour, not a genotype.
If you have unexplained joint pain with rashes, mouth ulcers, hair loss, fatigue or a rash that worsens in sunlight, that is worth a proper assessment. This page is not part of that assessment.
rs7329174 (ELF1). Identified through a GWAS in a Hong Kong Chinese cohort with replication in two further Asian populations, totalling 3,164 patients and 4,482 matched controls; OR 1.26, joint P = 1.47 x 10-8. ELF1 (E74-like factor 1) is an ETS-family transcription factor with established roles in T cell development and function. Database analysis showed transcripts initiated from three alternative first exons, with near-equivalent expression in peripheral blood mononuclear cells from patients and controls; the study did not establish a direct effect of the associated variant on those transcript levels.
Context. Lupus susceptibility includes HLA class II associations, interferon-pathway genes (IRF5, STAT4, IRAK1), complement deficiencies (rare but strong, particularly C1q), and immune-complex clearance genes such as FCGR variants. Rare monogenic causes exist — complement component deficiencies, DNASE1L3, and interferonopathies — and behave quite differently from the common variants recorded here.
Diagnosis and management. Classification uses combinations of clinical and immunological criteria; ANA is sensitive but not specific, while anti-dsDNA and anti-Sm are more specific. Renal involvement is assessed with urinalysis, protein quantification and biopsy where indicated. Treatment ranges from hydroxychloroquine for nearly all patients through corticosteroids and immunosuppressants to biologics, and is guided by organ involvement and activity rather than by genotype.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Systemic Lupus Erythematosus comes down to these specific, well-studied positions — not a diagnosis.
No. Diagnosis is made from the pattern of organ involvement together with antibody and complement testing. No variant, including this one, is used to diagnose, predict or grade the disease.
Because that is where this variant was found and replicated — 3,164 patients and 4,482 controls across three Asian populations. Lupus is more common and often more severe in populations that genetics has studied least, so this kind of evidence matters more here than in most places.
It clusters in families more than chance would explain, and relatives of patients have somewhat higher risk — but most people with lupus have no affected relative, and most relatives never develop it.
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