How well a pair of lungs works is heritable and measurable, and it is also mostly the result of what has been breathed. Both halves are true, and the second one is larger.
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.
Lung function is measured by asking someone to blow into a tube. Two numbers come out: how much air leaves in the first second (FEV1), and what share of the total that is (FEV1/FVC). The ratio is the one that says whether airflow is obstructed, which is how COPD is defined.
These are among the better predictors of illness and death in medicine, and they run in families.
A meta-analysis of 20,890 people across four large cohorts identified eight loci associated with FEV1/FVC. That is a real and reproducible result: the shape of a person's lungs and airways is partly inherited.
It is also small. Everything found together explains a modest share of the variation between people, and the variation between a smoker and a non-smoker dwarfs it.
Castaldi et al. 2015 studied lung function specifically in 9,919 current and former smokers, combining that with two further cohorts for a total of 13,532 people. It confirmed the well-known 15q25 nicotinic-receptor region — CHRNA3 and CHRNA5, the same genes most consistently linked to smoking behavior itself — and HHIP, both already tied to COPD, and added new associations at DBH, TGFB2, FAM13A, MMP3/MMP12, and RIN3. This is, by a wide margin, the largest single source behind this page's variant list: 161 of them come from this study — fitting exactly the smoking-and-environment framing below, since it measured lung function in people who actually smoked rather than a general population sample.
Artigas et al. 2015 took the opposite approach: a general-population study of 38,199 people of European ancestry, using newer imputation methods (the 1000 Genomes Project reference panel) to see further into the genome than earlier arrays could, with follow-up in 54,550 more people. It found 14 new loci plus two new signals at loci already known, including rs6856422, near NPNT, and rs61067109, near KCNS3 — both named directly in the paper. Seventeen of this page's variants come from here.
Wain et al. 2017 took a different sampling approach entirely: rather than a random population sample, the discovery stage deliberately selected 48,943 people from the extremes of the UK Biobank lung-function distribution — the people whose lung function was unusually high or low — then followed up in 95,375 more, raising the number of known independent lung-function signals from 54 to 97. A genetic risk score built from those loci showed a 3.7-fold difference in COPD risk between people in the highest and lowest 10% of that risk score. The paper specifically named CHRM3 as a target already being pursued by drugs in development for COPD and asthma — and rs6688537, in CHRM3, is one of this page's own variants. Twelve of this page's variants come from this study.
A 2018 meta-analysis of roughly 90,715 people across European, African, Asian and Hispanic/Latino ancestry found more than 50 new lung-function loci through both ancestry-specific and cross-ancestry analysis — fine-mapped using functional annotation, gene expression and ancestry-specific linkage-disequilibrium patterns rather than a single reference population. Among the newly implicated genes, KCNK2 and CDK12 stood out for having existing or plausible status as drug targets. This page holds 20 of this study's variants.
A 2026 study went a step further, studying lung-function traits and the respiratory diseases they underlie together rather than one at a time — most earlier work, including several of this page's own sources, looked at a single trait or disease in isolation. It found 25 new lung-function loci specifically in people of East Asian ancestry, then built a polygenic score, "PRSxtra," that pools signal across traits and ancestries rather than staying within one of each. That combined score significantly improved prediction of asthma, COPD and lung cancer compared with single-trait, single-ancestry scores in a diverse cohort from the All of Us Research Program — improving the most in exactly the populations single-ancestry lung-function GWAS have served least well. This page holds 15 of this study's variants.
Lung function is the clearest case on this site of a trait that is genuinely heritable and almost entirely about environment.
Both statements are true at once. Within a group of people who have breathed similar air, some of the difference is inherited. Between a person who smoked for thirty years and one who did not, almost none of it is.
A genotype here cannot tell anyone their lung function, and it certainly cannot tell them that smoking is safer for them. If anything the finding runs the other way: people with lower baseline function have less to lose before it matters.
Spirometry is cheap, quick and direct. If breathlessness, a persistent cough or an occupational exposure is the reason for the question, that test answers it — and it answers it about the lungs actually in the room rather than about a population average.
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 17 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.
Lutz SM et al. 2015, BMC genetics rs6842889 (near KRT18P51), rs11938745 (near KRT18P51), rs140330585 (CHRNA5), rs13118928 (near KRT18P51), rs7673195 (near GUSBP5), rs28381684 (MMP12), rs737693 (near MMP12), rs72983513 (near MMP12), rs12441426 (AGPHD1), rs191739273 (LINC00871), rs191755093 (LINC00871), rs7163730 (AGPHD1) and 2 more — PMID:26634245
Soler Artigas M et al. 2011, Nature genetics rs1036429 (CCDC38) — PMID:21946350
Hancock DB et al. 2010, Nature genetics rs3817928 (GPR126) — PMID:20010835
He Y et al. 2026, Nature genetics rs10860837 (WASHC3) — PMID:41565855
2026-02-28 · Multi-ancestry genome-wide association study and meta-analysis of lung function decline. Respiratory Research. 2026. DOI:10.1186/s12931-026-03565-x
GWAS of how fast lung function fades over time points to corticosteroids as a repurposing lead
This site's pulmonary function page describes genetics of lung capacity at a point in time; this study asks a different question -- what predicts how fast lung function declines over the years. Analyzing decline in FEV1, FVC and their ratio across 52,056 people (White, Black, Hispanic and Chinese American) in seven cohorts, stratified by ancestry and sex, it found 361 distinct genome-wide significant variants overlapping with previously known pulmonary-trait signals, and gene-level analysis implicated 38 genes with effects consistent across ancestries or decline measures. Annotation analysis found the implicated genes enriched for corticosteroid biosynthesis and metabolism pathways -- pointing toward a specific drug class already in clinical use for lung disease as mechanistically relevant to decline itself, not just symptom control. The drug-repurposing analysis identified 43 already-approved compounds targeting 8 of the implicated genes as candidates worth investigating specifically for slowing lung function decline. Of the significant variants tested in independent COPD-enriched cohorts, about 10% (4 variants) replicated -- a modest but real replication rate the authors report honestly rather than overstating. This site's pulmonary function page carries 203 variants; this entry documents a longitudinal-decline angle distinct from the page's existing point-in-time lung capacity variants.
The source. Hancock et al. (Nat Genet 2010) meta-analysed genome-wide association studies of FEV1 and FEV1/FVC in 20,890 participants of European ancestry from four CHARGE Consortium cohorts — the Atherosclerosis Risk in Communities study, the Cardiovascular Health Study, the Framingham Heart Study and the Rotterdam Study — identifying eight loci associated with FEV1/FVC.
The variants recorded here. rs2070600 in AGER, encoding the receptor for advanced glycation end-products (RAGE), which is constitutively expressed at high levels in lung tissue and participates in inflammatory signalling and alveolar repair; and rs11727189 in the GSTCD region of chromosome 4q24, a locus repeatedly implicated in lung function whose causal gene and mechanism remain unresolved.
Effect size and context. The variance in FEV1/FVC explained by all identified common variants is small in absolute terms and is dwarfed by the effect of smoking, occupational exposure and childhood respiratory illness. Spirometric measures are strong predictors of morbidity and mortality; the genetic contribution to them is real, reproducible and clinically inconsequential at the level of an individual.
Clinical boundary. Airflow obstruction is defined and diagnosed spirometrically, with post-bronchodilator FEV1/FVC below a defined threshold. No genotype is used in diagnosis, staging or management of COPD or asthma, and no position here modifies advice about smoking or occupational exposure.
What a 23andMe/AncestryDNA export or raw VCF can and can't tell you about Pulmonary Function (Lung Capacity) comes down to these specific, well-studied positions — not a diagnosis. 264 positions are linked to this page; the ones this page's own text discusses are shown first.
The studies behind these variants recruited participants from different ancestries — a result found in one population doesn't always transfer to another. Based on 239 of 264 linked studies with a resolved discovery ancestry.
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Pulmonary Function (Lung Capacity). MyGeneLog™. https://www.mygenelog.com/conditions/pulmonary-function
No, and the test that does takes about a minute. Spirometry measures the lungs in the room; these positions shift a population average by a little.
No. Within a group who have breathed similar air, some of the difference is inherited. Between a thirty-year smoker and a non-smoker, almost none of it is. If anything, lower baseline function means less margin before it matters.
FEV1 is how much air leaves the lungs in the first second; FVC is the total. The ratio says whether air is being obstructed on the way out, which is what defines COPD — a small total with a normal ratio is a different problem from a normal total that empties slowly.
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.