Polygenic · Oligogenic · Multifactorial

Complex-disease pedigree software — liability-threshold recurrence risk

Common complex disorders cluster in families but do not follow Mendelian inheritance. Evagene ships a liability-threshold recurrence-risk engine (Carter 1961; Falconer 1965; Reich, James & Morton 1972), empirical Smith / Carter / Harper recurrence-risk tables, and 20+ catalogued conditions — each with heritability, empirical recurrence risks by relationship, and a dedicated in-app help guide.

How the engine decides the base risk

Empirical table

Smith / Carter / Harper family-study figures keyed by degree of relationship — used when available.

Falconer fallback

Liability-threshold calculation from heritability (h²) and prevalence (K) when no empirical table exists.

Population baseline

When no affected relatives are present, recurrence risk equals the population prevalence K.

Four classical modifiers applied on top

Severity of proband — bilateral vs unilateral, severity grade on the individual disease record.

Carter-effect sex bias — e.g. pyloric stenosis M:F 5:1, DDH F:M 6:1.

Multiple affected close relatives — lookup table or doubling-per-extra-relative, capped at 4×.

Parental consanguinity — multiplier of (1 + 2F·h²).

The catalogued conditions

Every entry links to its in-app help page. Filter by inheritance class:

Cleft lip ± palate

K ≈ 1/1,000; 1st-degree recurrence ≈ 4%. Severity-sensitive.

Cleft palate only

Aetiologically distinct from CL±P; separate recurrence tables.

Hirschsprung's disease

RET + interacting loci; strong Carter-effect sex bias.

Type 1 diabetes

HLA-DR3/DR4; sibling recurrence ≈ 6%, MZ twin ≈ 30%.

Type 2 diabetes

Strong polygenic background + environment; MZ twin ≈ 90%.

Late-onset Alzheimer's

APOE ε4 a major modifier; distinguish from deterministic familial AD.

Idiopathic Parkinson's

Age-dependent. Distinguish from monogenic forms (LRRK2, PARK7, PINK1).

Ankylosing spondylitis

HLA-B27 carries most of the liability; h² ≈ 0.9.

Schizophrenia

Sibling ≈ 10%, offspring of one affected ≈ 13%; MZ twin ≈ 50%.

Bipolar disorder

Polygenic; shared liability with schizophrenia and major depression.

Major depression

Catalogued with liability estimates. In-app guide: coming soon.

Epilepsy

Heterogeneous; channelopathy / oligogenic aetiology mixed with common polygenic risk.

Pyloric stenosis

The classical Carter-effect disorder (M:F ≈ 5:1); mothers of affected girls have higher liability.

Neural tube defects

Folate a major environmental modifier; sibling recurrence ≈ 2–5%.

Congenital heart disease

Broad umbrella; if syndromic (e.g. cleft + CHD → 22q11.2), use Mendelian / chromosomal models.

Talipes equinovarus

Sex-biased (M predominant); classical multifactorial recurrence.

Developmental dysplasia of the hip

F:M ≈ 6:1 Carter-effect; breech + family history triggers screening.

Asthma

Shared atopic liability with eczema, allergic rhinitis; strong environmental component.

Atopic dermatitis

Filaggrin (FLG) loss-of-function a major locus; polygenic atopic background.

Coeliac disease

HLA-DQ2 / DQ8 almost required; 1st-degree recurrence ≈ 10%.

Essential hypertension

Highly polygenic; environment (salt, BMI) large modifier.

Obesity

Polygenic BMI liability + environmental; distinguish from monogenic MC4R.

Allergic rhinitis

Shared atopic liability with asthma and eczema.

Legend: M Multifactorial · P Polygenic · O Oligogenic. Classification follows the dominant aetiological model for each condition; all three share the liability-threshold engine.

When not to use the liability-threshold engine

Mendelian disorders — use the autosomal dominant / recessive / X-linked calculators instead.

Chromosomal or imprinted-region syndromes — e.g. 22q11.2 deletion presenting as cleft palate + CHD. Use the karyogram viewer and syndrome-specific guides.

Populations with very different K — e.g. high-HLA-B27 populations for ankylosing spondylitis. Verify local prevalence figures.

Environmental exposures not in the genetic model — folate for NTDs, allergen load for asthma, sodium for hypertension. Cover separately in counselling.