A cancer of plasma cells, the antibody-producing white blood cells. Three studies that built directly on each other tripled the number of confirmed risk loci in five years, converging on the same developmental process that makes a normal plasma cell in the first place.
Multiple myeloma is a cancer of plasma cells — the white blood cells that mature from B-cells specifically to manufacture antibodies. It disproportionately affects Black Americans, who have more than double the risk compared with other racial and ethnic groups in the US, a disparity current research attributes to a mix of social, environmental and biological factors that is not yet fully understood.
Chubb et al. 2013 ran the field's first large genome-wide scan, in 4,692 cases and 10,990 controls, finding four risk loci: 3q26.2, 6p21.33, 17p11.2 (TNFRSF13B) and 22q13.1 (CBX7, rs877529, P=7.63×10⁻¹⁶).
Mitchell et al. 2016 combined a meta-analysis of existing GWAS with a new scan and replication, reaching 9,866 cases and 239,188 controls. It confirmed all nine loci known by that point and discovered eight new ones — JARID2, ATG5, SMARCD3, CCAT1, CDKN2A, WAC, RFWD3 and PREX1 — bringing the total to 17. Eight of this page's variants come from here: rs34229995 (DTNBP1), rs7193541 (RFWD3), rs6066835 (PREX1), DTNB, ULK4, TNFRSF13B, a second CBX7 position, and ELL2.
Went et al. 2018 pushed further still: 9,974 cases and 247,556 controls, finding six more loci and bringing the confirmed total to 23. This study went beyond statistical association — it integrated gene expression, epigenetic profiling and Hi-C chromatin-contact data across all 23 loci, and concluded that disruption of developmental transcriptional regulators is the likely basis of susceptibility, consistent with altered B-cell differentiation as the key mechanism, alongside recurrently perturbed autophagy/apoptosis and cell-cycle pathways. Four of this page's variants — SP3, CEP120, a locus near CCDC71L, and one near POT1 — come from this study.
Read across all three studies, the story is coherent rather than scattered: myeloma susceptibility loci concentrate in genes that govern how a B-cell becomes a plasma cell in the first place, and in genes that maintain genome stability (DNA repair, telomere maintenance via POT1) once it has.
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 12 more positions 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.
Went M et al. 2024, Nature communications rs9856633 (near GEMIN2P2), rs7621631 (LRRC34), rs75341503 (DNAH11), rs5995688 (CBX7), rs6546615 (near KIF3C), rs3731222 (CDKN2A), rs6090899 (PREX1), rs75712673 (CCDC169-SOHLH2) — PMID:39103364
Verma A et al. 2024, Science (New York, N.Y.) rs1003099744 (near LINC00906), rs142614314 (ANXA13) — PMID:39024449
Duran-Lozano L et al. 2021, Blood cancer journal rs2285803 (PSORS1C2) — PMID:33875642
Swaminathan B et al. 2015, Nature communications rs57104699 (DNAH11) — PMID:26007630
Multiple myeloma is diagnosed with blood and urine tests for abnormal antibody proteins, bone marrow biopsy, and imaging for bone lesions — not by genotype. Treatment has advanced substantially in the last two decades (proteasome inhibitors, immunomodulatory drugs, monoclonal antibodies, and increasingly CAR-T cell therapy), decided by an oncologist based on disease stage and biology. None of that is decided by the variants on this page.
A recent review of the field's genetic architecture makes an important point explicitly: polygenic risk scores built from findings like these provide real insight into inherited susceptibility, but are not yet clinically actionable for risk stratification or screening in multiple myeloma, and remain research tools rather than something a doctor uses today.
The racial disparity in incidence is real and substantial, but is not explained by the common variants on this page alone — the germline loci found so far were discovered predominantly in European-ancestry cohorts, and the disparity's causes are still being actively researched across social, environmental and biological factors together.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Multiple Myeloma comes down to these specific, well-studied positions — not a diagnosis. 31 positions are linked to this page; the ones this page's own text discusses are shown first.
TERC · rs12638862
See detailed info →BCL2L11 · rs12711846
See detailed info →ULK4 · rs6763508
See detailed info →The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 17 of 31 linked studies with a resolved discovery ancestry.
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Multiple Myeloma. MyGeneLog™. https://www.mygenelog.com/conditions/multiple-myeloma
No. Multiple myeloma is diagnosed with blood and urine tests, bone marrow biopsy, and imaging. A recent review states plainly that polygenic risk scores from findings like these are not yet clinically actionable for risk stratification or screening — they remain research tools.
Because it is real and substantial — Black Americans have more than double the risk compared with other racial and ethnic groups in the US — and it is not explained by the common variants on this page, which were found predominantly in European-ancestry cohorts. The causes are still being actively researched.
Integrated analysis across all 23 loci points to disrupted developmental transcriptional regulators, consistent with altered B-cell differentiation — how a B-cell becomes an antibody-producing plasma cell — as the key mechanism, alongside disrupted autophagy/apoptosis and cell-cycle pathways.
Substantially by the numbers alone: the confirmed locus count went from 4 in 2013 to 17 in 2016 to 23 in 2018, each study building directly on the last with much larger sample sizes.
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.