The third leading cause of death in the world, and the one genetic finding that would change a doctor’s mind about it is a rare change this catalogue cannot see. What it can see are common variants, two of which act on the lungs by acting on how much somebody smokes.
Solid lines are connections this site curates. Dashed lines mean the two ends share a research paper — worth knowing, and not a claim that one explains the other.
COPD is airflow out of the lungs that is limited and does not fully come back. Two processes sit under that name — airways that are chronically inflamed and narrowed, and air sacs that have been destroyed so the lung loses its spring — and most people have some of each.
It is the third leading cause of death worldwide, responsible for around 3.5 million deaths in 2021. Smoking is the dominant cause where smoking is common; in much of the world the dominant cause is the smoke from cooking and heating indoors. Roughly a quarter of people with COPD never smoked at all, which is the fact most often left out of the conversation.
Four of the six positions on this page carry a trait that reads "post bronchodilator FEV1/FVC ratio", which sounds like a different subject. It is not. COPD is diagnosed by spirometry: you blow out as hard as you can, you are given an inhaler that opens the airways, and you blow again. FEV1 is how much comes out in the first second, FVC is how much comes out in total, and if the ratio between them is below 0.70 after the inhaler, that is the diagnosis.
So the trait name is the diagnosis written as the number it is made of. A study of that ratio is a study of COPD, taken one step closer to what is actually measured.
Two of these positions are in CHRNA3 and CHRNA5, which encode parts of a nicotine receptor. The same cluster appears on this site under smoking behaviour and under lung cancer, and that is the point rather than a coincidence.
These variants are associated with how heavily somebody smokes. Smoking damages lungs. So a variant can be genuinely associated with a lung measurement while doing nothing to lung tissue at all — its effect travels through a behaviour. Untangling how much of such an association is the behaviour and how much is anything else is difficult, and a headline that says "gene linked to lung disease" has usually not tried.
There is one genetic cause of COPD that changes what a doctor does: alpha-1 antitrypsin deficiency. Rare changes in SERPINA1 leave the lung without a protein that protects it from its own enzymes, and the result is COPD that arrives decades early, often in someone who barely smoked. It matters because it is actionable — it changes how urgently smoking must stop, it prompts testing of relatives, and a specific treatment exists.
This catalogue holds no SERPINA1 variant, because the studies it is built from scan for common variants and these are rare ones found by sequencing or by measuring the protein in blood. Guidance from WHO and from the respiratory societies is that everybody diagnosed with COPD should be tested for it once, and it remains widely under-diagnosed.
So the honest summary of the genetics on this page is: the variants we can show you shift risk slightly, and the one that would change your treatment is not among them. Ask about the test rather than reading a file.
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 46 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.
Sakornsakolpat P et al. 2019, Nature genetics rs2119568 (THSD4), rs17759204 (CACNA2D3), rs72673419 (C1orf87), rs62191105 (TWIST2), rs10760580 (COL15A1), rs629619 (DENND2D), rs72626215 (DMWD), rs35584079 (ITPK1), rs12466981 (EML4), rs9273404 (HLA-DQB1), rs11118406 (SLC30A10), rs4523894 (ADAMTSL3) and 15 more — PMID:30804561
Moll M et al. 2021, American journal of physiology. Lung cellular and molecular physiology rs11155242 (ADGRG6), rs2523989 (TRIM31), rs11938093 (BTC), rs13195509 (BTN2A1), rs1129740 (HLA-DQA1), rs2287749 (ADAM19) — PMID:33909500
Zhou W et al. 2022, Cell genomics rs9272456 (HLA-DQA1), rs12232354 (GALK2), rs62201158 (LINC01807), rs12908092 (THSD4) — PMID:36777996
Verma A et al. 2024, Science (New York, N.Y.) rs151176846 (CHRNA4), rs13148031 (near KRT18P51) — PMID:39024449
Joo J et al. 2021, AMIA ... Annual Symposium proceedings. AMIA Symposium rs2001546 (CDC123), rs2158101 (CARINH) — PMID:35308900
Sakaue S et al. 2021, Nature genetics rs73038469 (CYP2B7P), rs114904431 (DPYD) — PMID:34594039
Hobbs BD et al. 2017, Nature genetics rs17035917 (ARHGEF38), rs17707300 (CCDC101) — PMID:28166215
Ishigaki K et al. 2020, Nature genetics rs2288450 (COQ8B) — PMID:32514122
2026-08-27 · Cross-Trait Genome-Wide Association Study Identifies Shared Genetic Architecture Between COPD and Retinal Vascular Phenotypes. International Journal of Chronic Obstructive Pulmonary Disease. 2026. DOI:10.2147/copd.s624726
COPD comes with systemic vascular dysfunction, and this study asked whether that overlap is genetic by combining GWAS summary statistics for COPD with 17 retinal vascular traits -- retinal blood vessels being a non-invasive window into microvascular health generally. It found significant genetic correlation between COPD and 10 retinal vascular traits, with 3,846 shared significant variants across 2,246 unique loci, and recurrent shared signals at five chromosome regions including 15q25.1 -- the same nicotinic-receptor gene cluster (CHRNA3/CHRNA5) already on this site's own COPD page. The study's smoking-adjusted analysis specifically found that this 15q25.1 signal was attenuated once smoking was accounted for, while several other shared loci remained -- direct evidence that at least part of the COPD/retinal-vasculature overlap runs through smoking behavior itself, not just a shared disease process independent of it. This site does not currently have a retinal-vascular-traits page to also attach this finding to, so it is recorded here at the COPD condition level, adding context to the existing rs72740964 (CHRNA5) and rs147144681 (CHRNA3) variants rather than introducing new ones -- the study reports its 56 shared loci by chromosome band, not by the individual rsIDs this site's variant pages require.
Diagnosis. Spirometry before and after a bronchodilator, with post-bronchodilator FEV1/FVC below 0.70 as the threshold. Symptoms alone do not settle it, and neither does a chest X-ray; a great deal of COPD is undiagnosed because the test is never done.
What the common variants do. FAM13A, TGFB2 and the region near HHIP are among the better-replicated associations with COPD and with lung function. Each shifts risk by a small amount, none is diagnostic, and together they explain a small fraction of who develops the disease.
Smoking is not the whole story, in either direction. Most smokers do not develop COPD and about a quarter of people with COPD never smoked. Both facts point at the same thing: susceptibility differs between people, and only a small part of that difference has been located.
Lung function is set partly before anything goes wrong. Some people reach adulthood with a lower peak lung function and cross the COPD threshold later without any unusual rate of decline. Childhood infections, prematurity and early exposures matter to that, which is why some of the genetics of COPD overlaps with the genetics of lung growth rather than of lung damage.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Chronic Obstructive Pulmonary Disease (COPD) comes down to these specific, well-studied positions — not a diagnosis. 56 positions are linked to this page; the ones this page's own text discusses are shown first.
PITPNA · rs140948272
See detailed info →CDH13 · rs114132812
See detailed info →SGCD · rs10056066
See detailed info →CHRNA4 · rs151176846
See detailed info →near KRT18P51 · rs13148031
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 12 of 56 linked studies with a resolved discovery ancestry.
Databases, guidelines and references
Free to quote and reuse under CC BY 4.0. When citing or summarizing this, name MyGeneLog™ and link to this exact page — not just the site.
Chronic Obstructive Pulmonary Disease (COPD). MyGeneLog™. https://www.mygenelog.com/conditions/chronic-obstructive-pulmonary-disease
In two ways. Common inherited variants each add a little to susceptibility, and some act through how much a person smokes. Separately, alpha-1 antitrypsin deficiency, caused by rare SERPINA1 variants and inherited in an autosomal recessive pattern, accounts for a small percentage of cases and is the only genetic finding that changes management.
They shift risk by a small amount and are not a test. The strongest thing anybody can say about their own risk of COPD is whether they smoke and what air they breathe indoors, and that is not a genetic statement.
Because that is how COPD is diagnosed. You blow into a spirometer, you are given an inhaler, and you blow again. A ratio of FEV1 to FVC below 0.70 after the inhaler is the diagnosis, so a study of that ratio is a study of this disease.
It is the one genetic cause of COPD that changes treatment, caused by rare SERPINA1 variants, and it is not on this page because this catalogue holds no SERPINA1 variant — the studies behind these pages look for common variants. Guidance is that everybody diagnosed with COPD is tested for it once, and it is widely missed.
Through the person rather than the lung. Those variants are associated with how heavily somebody smokes, and smoking damages lungs, so the association is real while the gene may be doing nothing to lung tissue itself.
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.