Visible varicose veins, skin changes, and occasionally venous ulcers, caused by faulty vein valves that let blood pool in the legs. Common enough that most people know someone affected, yet this page's variant comes from the first genome-wide study of the condition ever conducted.
Chronic venous disease covers a spectrum: visible varicose veins at the mild end, skin changes and venous ulcers at the more serious end, all caused by faulty valves in the leg veins that let blood pool instead of flowing back toward the heart. It is common — most people know someone affected — and usually cosmetic or mildly symptomatic, occasionally progressing to skin breakdown that needs treatment.
Despite how common it is, Ellinghaus et al. 2017 was the first genome-wide association study ever conducted on it.
The study — 2,269 cases and 7,765 controls (from an initial 4,942-person German cohort, with further discovery and replication) — tested over 1.93 million variants and identified two loci. EFEMP1 was the study's strongest finding. KCNH8, the gene the variant on this page sits in, was reported as a suggestive rather than fully confirmed association — weaker evidence than EFEMP1, stated here rather than presented as equally established.
Both loci showed evidence of acting as expression quantitative trait loci — positions that influence how much of a gene's product gets made — in relevant tissue. The paper highlights EFEMP1, a gene involved in the extracellular matrix, as warranting further study for its role in blood vessel formation: a mechanistically sensible direction, given that faulty vein structure is the whole basis of the disease.
2026-04-22 · Genome-Wide Association Study of Chronic Venous Insufficiency and Lymphedema in the Million Veteran Program. Circulation: Genomic and Precision Medicine. 2026. DOI:10.1161/circgen.125.005442
First large genetic study of chronic venous insufficiency and lymphedema finds 11 risk variants
Lymphedema -- fluid accumulation from impaired lymphatic drainage, often occurring alongside chronic venous insufficiency (CVI), cancer or obesity -- has had its genetic contributors understudied despite well-known clinical risk factors. This study analyzed Million Veteran Program participants without cancer, comparing 34,664 people with CVI only, 2,452 with lymphedema only, and 3,283 with both, against 367,684 controls. It identified 11 genome-wide significant variants overall: 8 specific to CVI, plus additional signals for lymphedema and the combined phenotype. This is a substantial addition to a condition this site currently covers with just 1 variant, and the first study to separate genetic contributions to CVI alone, lymphedema alone, and their co-occurrence rather than treating them as one trait.
Chronic venous disease is diagnosed by physical examination and, when needed, ultrasound — not by genotype. Compression stockings, lifestyle measures, and procedures to close or remove faulty veins are the established treatments, chosen based on severity and symptoms rather than any variant listed here.
The KCNH8 signal on this page is explicitly the weaker of the study's two findings. That distinction matters: a "suggestive" association is a real, reported result worth tracking as further studies come in, not the same strength of evidence as a confirmed genome-wide significant locus.
Venous thromboembolism — blood clots in the veins — is a different condition with its own genetics, despite sharing the word "venous." Chronic venous disease is about faulty valves and pooling blood, not clotting.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Chronic Venous Disease comes down to these specific, well-studied positions — not a diagnosis.
Databases, guidelines and references
No. It is diagnosed by physical examination and, when needed, ultrasound. This variant comes from a genome-wide association study and is not used diagnostically.
No — EFEMP1 was the study's strongest, fully confirmed finding. KCNH8, the gene on this page, was reported as a suggestive association, which is weaker evidence, and this page states that distinction rather than treating both genes as equally established.
No — different condition, despite sharing the word "venous." Chronic venous disease is about faulty vein valves letting blood pool; venous thromboembolism is about clot formation. Each is catalogued separately.
This 2017 study was the first genome-wide association study of chronic venous disease ever conducted, despite how common the condition is — a reminder that "common" and "well-studied genetically" do not always go together.
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