A progressive scarring disease of the lungs with a strong genetic component: two genome-wide studies found risk variants in TOLLIP, SPPL2C and AKAP13 beside the well-known MUC5B signal — and one TOLLIP variant that protects against getting the disease but predicts worse survival in those who get it anyway.
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive disease in which lung tissue is gradually replaced by scar, with high mortality, an uncertain cause and few treatments. "Idiopathic" means no cause is found in the individual case — yet the disease has a clear genetic component, and genome-wide studies have mapped part of it. This page holds 2 variants from two of those studies.
Noth et al. 2013 ran a three-stage genome-wide study in European-American patients. Stage one compared 542 patients with 542 matched controls and flagged 20 loci; stage two, in 544 patients and 687 controls, brought six positions to genome-wide significance: three in TOLLIP, one in MUC5B — both on chromosome 11 — one in MDGA2 and one in SPPL2C. A third stage of 324 patients and 702 controls confirmed all of them except the MDGA2 signal. This page's rs17690703, in SPPL2C, is one of the confirmed six.
The study's most unusual finding was about survival rather than risk. One TOLLIP variant, rs5743890, has a minor allele that protects against developing IPF — yet among 683 patients followed over time, those who carried that protective allele and developed the disease anyway had a higher risk of death (hazard ratio 1.72, 95% confidence interval 1.24 to 2.38). Carriers of the three TOLLIP minor alleles also had lower TOLLIP expression — by about 20%, 40% and 50% respectively — which the authors read as evidence that the gene matters to the disease, not just to the statistics.
Allen et al. 2017 started with 602 UK patients and 3,366 UK Biobank controls matched for age, sex and smoking, then followed up in 2,158 patients and 5,195 controls from two US consortia. They found a new genome-wide signal near AKAP13 — this page's rs62025270, odds ratio 1.27 (95% confidence interval 1.18 to 1.37) — and showed that its risk allele went with higher AKAP13 messenger RNA in lung tissue. The same study confirmed the two best-established IPF signals: MUC5B rs35705950, with an odds ratio of 2.89 (2.56 to 3.26), and DSP rs2076295, at 1.44 (1.35 to 1.54).
MUC5B rs35705950 is the strongest common genetic risk factor for IPF in both studies above — an odds ratio near three is enormous for a common variant — and it is not on this site. The reference database records more than two alleles at that position, and this site's genotype tables are built only for positions with two, so the collector holds it back rather than guess. We say so here because anyone reading about IPF genetics will meet MUC5B first, and should find it named on this page even though it has no page of its own. DSP rs2076295 is in the catalogue's queue and will attach to this page when it arrives.
IPF is diagnosed from high-resolution CT imaging, lung function tests and, when needed, lung biopsy — never from a genotype. Neither variant on this page, and none of the variants named in the studies above, is used by any guideline to diagnose IPF, to decide who should be screened, or to choose between antifibrotic treatments.
The TOLLIP survival finding is the kind of result that sounds actionable and is not, yet: it comes from 683 patients in one study, and the authors present it as evidence about the gene's importance in the disease, not as a prognostic test. A person with IPF, or with a family history of it, gets more from a pulmonologist than from any position on this page.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Idiopathic Pulmonary Fibrosis comes down to these specific, well-studied positions — not a diagnosis.
near SLC35B3 · rs76782037
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 2 of 3 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
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Idiopathic Pulmonary Fibrosis. MyGeneLog™. https://www.mygenelog.com/conditions/idiopathic-pulmonary-fibrosis
A chronic, progressive lung disease in which lung tissue is gradually replaced by scar tissue. "Idiopathic" means no cause is identified in the individual case, but the disease has a clear genetic component that genome-wide studies have partly mapped.
MUC5B. A common variant near it, rs35705950, carries an odds ratio of about 2.89 — very large for a common variant — and was confirmed in both studies behind this page. It is not on this site yet because the reference database records more than two alleles at that position.
One TOLLIP variant has a minor allele that protects against developing IPF, but among 683 patients who developed the disease anyway, carriers of that protective allele had a higher risk of death (hazard ratio 1.72). Carriers also had lower TOLLIP expression. It is a finding about the gene's role, not a test used in care.
No. IPF is diagnosed from CT imaging, lung function tests and sometimes biopsy. The variants here are population-level findings from studies of a few thousand people; none is used to predict, screen for or diagnose the disease in an individual.
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