Complex traits: familial risk, twins, heritability and polygenic scores
Common diseases run in families without a simple pattern; twin studies, heritability and polygenic scores measure how much genes contribute.
Key facts
- Multifactorial (threshold) model: many genes and environmental factors add up to a liability; disease appears above a threshold.
- Recurrence risk rises with the number of affected relatives, closeness of relationship, severity in the affected person, and when the affected person is of the less commonly affected sex.
- Twin studies: identical twins share almost all their DNA and fraternal twins about half; a much higher concordance in identical twins points to genes, and concordance below 100 % shows the environment's share.
- Heritability is the proportion of variation in a trait within a population explained by genetic differences; it describes a population in a given environment, not an individual.
- A polygenic risk score adds up many common variants of small effect found by genome-wide association studies; it can identify people at several-fold higher risk of, for example, coronary disease.
In detail
- Gene–environment interactions: factor V Leiden with oral contraceptives raises clot risk much more than either alone; APOE ε4 raises Alzheimer risk.
- Some multifactorial disorders have strong single loci: HLA-DQ2/DQ8 in coeliac disease, HLA in type 1 diabetes, RET variants in Hirschsprung disease.
- Polygenic scores work less well in people whose ancestry is under-represented in the studies that built them, which risks widening health inequalities.
- Adoption studies separate shared genes from shared upbringing.
- Also called
- Multifactorial inheritance, Polygenic risk score
Clinical notes
- For a couple with one child with a multifactorial birth defect (cleft lip, neural tube defect), empirical recurrence risks from population studies guide counselling.
- Polygenic scores are not yet routine care; family history remains the practical tool.
Test yourself
Think of the answer, then tap the question to see it.
What does a heritability of 80 % for height mean?
In that population and environment, 80 % of the variation in height between people is explained by genetic differences; it says nothing about one person.
What do twin concordance studies show?
Higher concordance in identical than in fraternal twins points to a genetic contribution; concordance below 100 % in identical twins shows environmental influence.
Why do polygenic scores perform worse in some populations?
They were built mostly from European-ancestry data, so their variants and weights transfer poorly to other ancestries.
Connections
Educational information, not medical advice. For any symptom, see a health professional.
Sources: What is heritability?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); What are genome-wide association studies?: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Polygenic Risk Score (PRS) (National Human Genome Research Institute (NHGRI), 2026).
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Representative model, for educational purposes only.