Lupus (SLE) Genetic Risk — lupus has approximately 50% heritability, and monogenic forms caused by complement deficiency, TREX1, or DNASE1L3 variants require different treatment strategies than typical autoimmune SLE.
Whole genome sequencing evaluates complement genes (C1Q, C2, C4), interferonopathy genes (TREX1, DNASE1L3, RNASEH2A/B/C), HLA haplotypes (DRB1), and all additional lupus-associated variants — distinguishing monogenic from polygenic lupus.
Lupus (SLE) — Genetic Risk
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease affecting approximately 200,000-300,000 people in the US, with ~50% heritability. The genetic architecture includes both polygenic susceptibility (HLA-DR2, HLA-DR3, ITGAM, STAT4, IRF5, BLK, TNFAIP3, and >100 additional GWAS loci) and rare monogenic forms. The strongest common genetic risk factor is the HLA class II region — HLA-DRB1*03:01 and HLA-DRB1*15:01 each confer approximately 2-3 fold increased risk. Copy number variation at C4 (complement component 4) is a major genetic determinant — low C4 copy number substantially increases lupus risk.
Monogenic lupus represents approximately 1-3% of all SLE and is critically important to identify. Complement deficiency — particularly C1q (>90% develop lupus), C1r/C1s, C2, and C4 homozygous deficiency — causes severe early-onset lupus through impaired clearance of apoptotic debris and immune complexes. TREX1 deficiency causes Aicardi-Goutières syndrome/familial chilblain lupus through accumulation of endogenous nucleic acids that activate the type I interferon pathway. DNASE1L3 deficiency causes hypocomplementemic lupus with anti-dsDNA antibodies. These monogenic forms have specific pathogenic mechanisms that influence treatment selection.
Treatment implications of genetic lupus subtyping are emerging. Anifrolumab (Saphnelo), an anti-type I interferon receptor antibody, is FDA-approved for moderate-to-severe SLE and is mechanistically most relevant in patients with high interferon signatures — including those with interferonopathy-pathway variants (TREX1, IFIH1, RNASEH2). Complement-deficient lupus may respond to fresh frozen plasma (replacing the missing complement component) or complement inhibitors, but does NOT respond to standard immunosuppression targeting autoimmune pathways. Belimumab (anti-BLyS) targets B-cell activation and may be particularly effective in patients with BLK or BANK1 risk variants.
C1q deficiency causes lupus in >90% of carriers — the highest penetrance of any lupus gene. This complement-deficiency lupus has a different pathogenic mechanism than autoimmune SLE and may not respond to standard immunosuppressive therapy.
Monogenic lupus (complement deficiency, interferonopathy) does not respond to standard immunosuppression. Molecular diagnosis identifies the 1-3% of lupus patients who need different treatment — and the emerging genetic biomarkers for targeted therapies like anifrolumab.
Complement-deficient lupus requires complement replacement, not immunosuppression — wrong treatment delays effective therapy for years
C1q-deficient patients produce lupus-like disease through impaired clearance of apoptotic cells and immune complexes — a waste-disposal problem, not a primary autoimmune attack. Standard lupus immunosuppression (mycophenolate, cyclophosphamide) addresses the wrong mechanism. Fresh frozen plasma infusion (providing functional C1q) can produce dramatic clinical improvement. Without genetic complement deficiency testing, these patients receive escalating immunosuppression for 'treatment-resistant lupus' — when the correct diagnosis would redirect therapy entirely.
C4 copy number variation is the strongest common genetic determinant of lupus risk — WGS quantifies C4A and C4B gene copies
The C4 locus on chromosome 6 is one of the most structurally complex regions in the human genome — C4A and C4B genes exist in variable copy numbers (0-6 copies each). Low C4 copy number (particularly low C4A) substantially increases lupus risk, while high copy number is protective. Standard genetic testing does not evaluate C4 copy number. WGS reads across the entire C4 locus, enabling copy number quantification that provides the most important common genetic lupus risk assessment.
Your full DNA (not just a part of it)
Traditional genetic testing looks at narrow sets of genes, missing most parts of your genome. We sequence your full genome — every gene and every region between genes.
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Easy to read and with answers you and your doctor can act on. Not a file to interpret — 200+ clinical reports, organized by category.
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Your DNA does not change, but genome science is accelerating. Every month, new variant-disease associations are discovered. We validate these findings and update your reports automatically. Your test becomes more valuable every year.
The results doctors bring to their hardest cases.
Forty years of uncertainty. One test.
A patient had spent decades in the UK healthcare system without a diagnosis. Dante data, accepted by NHS clinical teams at Queen Elizabeth University Hospital Glasgow, identified Noonan Syndrome and a RUNX1 leukemia-associated variant that had gone undetected. After 40 years, they finally had an answer.
A complete read delivers a complete picture.
A patient came to Dante to investigate periodic paralysis. Reading the complete genome identified a concurrent hereditary cardiac finding — Brugada syndrome — that their doctor confirmed with an ECG. The result also explained a family member's unresolved cardiac history. One test. Every answer in it.
Sequenced in 2019. The data worked in 2021.
Jennifer sequenced her genome with Dante two years before her breast cancer diagnosis. When treatment began, Dante's pharmacogenomics data showed her prescribed chemotherapy would cause serious adverse effects. Her doctor selected an alternative — and she started effective treatment from day one.
Every genetic question deserves a complete answer.
Whether you are searching for answers today or protecting your health for tomorrow, a complete read of your entire genome is the only place to start.
It runs in your family. Now you can know if it runs in your genes.
Your genome contains inherited variants associated with medical conditions like cardiac, cancer, and neurological. We read all of them — with the clinical depth to give the result meaning.
Learn more →When traditional lab tests say you're fine. And you know you're not.
Standard diagnostic tests check for a pre-selected set of answers. We sequence your full DNA — including parts that no test was designed to check. If the answer is in your genome, we will help you find it.
Learn more →Your diagnosis may be right. Your treatment plan may be incomplete.
Your genes determine which treatments are most likely to work — and which are not. We give your doctor the tools and insights to inform your treatment plan.
Learn more →You want to know before something forces the question.
Some people don't wait for a diagnosis or a family history to act. Whole genome sequencing gives you the complete genetic picture now — so you and your doctor can make informed decisions before anything becomes urgent.
Learn more →You already took a DNA test. Here's what it couldn't tell you.
Most consumer DNA tests read less than 0.1% of your genome. We read all of it.
Learn more →Clinical-grade results. Chosen by individuals, trusted by doctors for their most complex cases.
Dante Genome Test helped specialists at a UK national acute hospital in the identification of Noonan Syndrome and a rare leukemia-associated genetic variant that had gone undetected. That result changed the medical care of the patient.
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Common questions about whole genome sequencing.
What is the difference between whole genome sequencing and a targeted genetic test?
Targeted genetic tests — including standard hereditary cancer panels — read a pre-defined list of known variants in a specific set of genes. They are designed to find what they already know to look for. Whole genome sequencing reads your entire genome: all 6 billion base pairs, every gene, every region between genes. A Mayo Clinic study published in JAMA Oncology found that standard testing guidelines missed more than half of patients with inherited cancer mutations. Genome Test does not have a fixed list.
What will I receive when my results are ready?
Your Dante Genome delivers 200+ physician-ready reports organized by clinical category — hereditary cancer, cardiac conditions, rare diseases, pharmacogenomics, carrier status, and more. Reports are delivered to your secure Genome Manager and are formatted for direct clinical use. Your genome data is permanently retained and re-analyzed automatically as science advances.
What happens if a clinically significant variant is found?
If a pathogenic or likely-pathogenic variant is identified, it will be clearly flagged in your physician-ready report with clinical context, published evidence, and recommended next steps. We recommend sharing any clinically significant finding with your physician or a genetic counselor, who can guide decisions about surveillance, risk reduction, or cascade testing for family members.
How is this different from a consumer DNA test like 23andMe or AncestryDNA?
Consumer DNA tests use genotyping chips that read less than 0.1% of your genome — a tiny pre-selected set of common variants. They are optimized for ancestry and population-level traits, not clinical genetic findings. The Dante Genome Test sequences 100% of your genome at 30X coverage, the same standard used in clinical diagnostic settings. The two tests are not comparable in scope, methodology, or clinical utility.
How long does it take to get results, and how are they delivered?
Your collection kit ships within 48 hours of ordering. Once your sample arrives at our CLIA-certified laboratory, sequencing and analysis takes 6–8 weeks. Results are delivered securely to your Genome Manager, where you can access your reports, share them with your physician, and receive automatic updates as new findings are validated against your genome.
We work with patient advocacy groups worldwide.
Dante Labs works with patient advocacy groups of any size — for Lupus (SLE) — Genetic Risk and other conditions, rare and common. We support groups in any country, including virtual patient advocacy groups.
We can provide customized reports, group discounts, and packages tailored for your members. Please reach out using the form and we'll be in touch within two business days.
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One kit, sent to your home. Your entire genome sequenced at the clinical standard used for diagnostic decisions. 200+ physician-ready reports delivered to your Genome Manager in 6–8 weeks — permanent and updated as science advances.
Ships within 48 hours · Results in 6–8 weeks
