Emphysema can be hereditary. The clearest genetic cause is a condition called alpha-1 antitrypsin deficiency (AATD), which accounts for roughly 1 to 3% of all COPD cases and can trigger emphysema decades earlier than usual. But genetics also play a subtler role: even without a single identifiable gene, inherited variations across your DNA can raise your susceptibility to emphysema, especially if you smoke.
How Genetic Emphysema Works
Your lungs rely on a protective protein called alpha-1 antitrypsin (AAT) to keep immune-system enzymes in check. White blood cells release powerful enzymes to fight infection, but those same enzymes can chew through healthy lung tissue if nothing stops them. AAT acts as the brake. In people with AATD, the body produces too little functional AAT, and those enzymes destroy the tiny air sacs (alveoli) where oxygen enters the bloodstream. Over time, this damage becomes emphysema.
The gene responsible is called SERPINA1. Everyone inherits two copies, one from each parent. The normal version is labeled “M,” so a person with two normal copies has the MM genotype and produces healthy levels of the protective protein. The most clinically significant variant is the “Z” allele. Someone who inherits two Z copies (the ZZ genotype) has severely reduced AAT levels, typically producing only about a quarter of the normal amount. An estimated 235,000 people worldwide carry the ZZ genotype, with about half of them living in Europe.
Emphysema normally appears between ages 60 and 80. In people with severe AATD, it can develop before age 55, sometimes much earlier. Rarer genetic mutations in genes that affect connective tissue or lung structure can cause emphysema in infancy or early childhood, though these conditions are extremely uncommon.
What Each Genotype Means for Risk
Not every gene combination carries the same level of danger. Here’s how the main genotypes compare:
- ZZ (two deficient copies): The highest-risk group. In one study of people with COPD, 100% of ZZ individuals had moderate to severe disease. They also scored significantly worse on measures of breathlessness, exercise capacity, and quality of life compared to people without the variant.
- SZ or other compound combinations (one Z copy plus another variant): Still high risk. Six out of seven people with these combinations had moderate to severe COPD in the same study, with notably impaired small-airway function and AAT levels roughly 40% of normal.
- MZ (one normal copy, one Z copy): This is the carrier state, and it’s far more common than ZZ. Carriers produce about 60% of normal AAT levels. On its own, carrying one Z allele modestly increases emphysema measures, but the real danger is smoking: MZ carriers who smoke face a 5 to 10 times greater risk of developing COPD compared to MM smokers.
That last point is critical. If you’re an MZ carrier and never smoke, your odds of serious lung disease remain relatively low. Smoking removes the safety margin that your one good gene copy provides.
Genetics Beyond a Single Gene
AATD is the most dramatic example of hereditary emphysema, but it’s not the whole story. Researchers have identified numerous spots across the genome that each contribute a small amount of risk for reduced lung function, COPD, and emphysema. When scientists combine these into a polygenic risk score (essentially a tally of how many risk-raising variants you carry), higher scores correlate with more emphysema on CT scans, thicker airway walls, and reduced lung growth during development.
This means two smokers with identical habits can have very different outcomes partly because of their genetic background. One person’s lungs may tolerate decades of exposure while another’s deteriorate rapidly. Family history of COPD or emphysema, even without a known AATD diagnosis, is a meaningful signal that your genetic deck may be stacked toward lung vulnerability.
How Hereditary Emphysema Is Diagnosed
Testing for AATD is straightforward: a simple blood draw measures your AAT protein level. If that level falls below a certain threshold (roughly 57 mg/dL), your doctor will order genetic testing to identify which SERPINA1 variants you carry. Levels above about 100 mg/dL generally rule out clinically significant deficiency, but results in the gray zone between those numbers warrant further investigation with specialized testing.
Major respiratory guidelines recommend testing anyone diagnosed with COPD or emphysema at least once for AATD, regardless of age or smoking history. Testing is also recommended for people with a family member who has the deficiency, unexplained liver disease, or emphysema that appears unusually early. Despite these recommendations, AATD remains widely underdiagnosed. Many people carry the ZZ genotype for years before anyone thinks to check.
Treatment for Genetic Emphysema
People with hereditary emphysema receive the same baseline treatments as anyone with COPD: inhalers, pulmonary rehabilitation, and, most importantly, complete avoidance of smoking. But those with confirmed severe AATD have an additional option: augmentation therapy. This involves regular infusions of the missing AAT protein, sourced from donated blood plasma. It’s currently the only disease-modifying treatment specifically approved for AATD.
A major clinical trial (the RAPID trial) demonstrated that augmentation therapy slows the rate of lung tissue loss as measured by CT scans. It doesn’t reverse existing damage, but it puts the brakes on further destruction. Because it slows emphysema progression, researchers predict it will improve long-term survival, though the therapy requires ongoing infusions, typically weekly, for life.
For carriers (MZ genotype), augmentation therapy is not currently recommended. The most impactful intervention for carriers is never smoking or quitting immediately. Given their 5 to 10 times elevated risk when exposed to tobacco, removing that trigger is the single most protective step an MZ carrier can take.
What This Means for Families
Because AATD follows a straightforward inheritance pattern, the implications for relatives are clear. If one parent carries the ZZ genotype, every child will inherit at least one Z allele, making them at minimum an MZ carrier. If both parents are MZ carriers, each child has a 25% chance of being ZZ, a 50% chance of being MZ, and a 25% chance of being MM. Siblings of someone diagnosed with AATD should get tested even if they feel perfectly healthy, since early identification allows for protective lifestyle changes and monitoring before lung damage accumulates.
For the broader genetic risk that doesn’t trace to a single gene, there’s no equivalent test you can act on today. But a family pattern of COPD or emphysema, particularly in people who smoked lightly or never smoked, should raise your awareness. Protecting your lungs from smoke, air pollution, and occupational dust becomes especially important when your family history suggests inherited vulnerability.