Multifactorial and polygenic inheritance and polygenic risk scores
The liability-threshold model, empirical recurrence risks, heritability from twin studies, and what a polygenic risk score can and cannot tell a patient, with worked numbers.
Tier 2Medical sciences concept
Written with AI assistance and fact-checked against the sources below. For exam study, not clinical decisions. How notes are made
At a glance
- Most common diseases (coronary disease, type 2 diabetes, asthma, schizophrenia) and congenital malformations (neural tube defects, cleft lip, congenital heart disease, pyloric stenosis) are multifactorial: many genes of small effect plus environment.
- Polygenic describes the genetic part (many loci, each with odds ratios around 1.05 to 1.2). Multifactorial adds environment.
- Families show clustering without a Mendelian ratio. Recurrence risks are empirical, taken from population data.
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Sources
- Thompson & Thompson Genetics and Genomics in Medicine (9th ed.)Elsevier (Cohn, Scherer and Hamosh, eds), 2023
- Torkamani A, Wineinger NE, Topol EJ. The personal and clinical utility of polygenic risk scores. Nat Rev Genet 2018;19:581-90Nature Reviews Genetics, 2018
- Khera AV et al. Genome-wide polygenic scores for common diseases identify individuals with risk equivalent to monogenic mutations. Nat Genet 2018;50:1219-24Nature Genetics, 2018
- Martin AR et al. Clinical use of current polygenic risk scores may exacerbate health disparities. Nat Genet 2019;51:584-91Nature Genetics, 2019
- Talmud PJ et al. Use of low-density lipoprotein cholesterol gene score to distinguish patients with polygenic and monogenic familial hypercholesterolaemia: a case-control study. Lancet 2013;381:1293-301The Lancet, 2013
- Kaprio J et al. Concordance for type 1 (insulin-dependent) and type 2 (non-insulin-dependent) diabetes mellitus in a population-based cohort of twins in Finland. Diabetologia 1992;35:1060-7Diabetologia, 1992
- Australian guideline for assessing and managing cardiovascular disease riskAU/NZCommonwealth of Australia (Department of Health and Aged Care), 2023
- Last updated
- 14 November 2026
What changed
- 14 November 2026 Personal emails, About story and Australian-style copy