Extended Data Fig. 1

Selection coefficients for a large parameter space of onset. a–c, Cumulative incidence of disease onset with age according to change in Mean Age at disease Onset (MAO) and First Age at disease Onset (FAO, with FAO from age 20 to MAO − 5 yrs). If disease onset is confounded with morbidity or full incapacitation, cumulative risk is 1-L^d(x), where L^d(x) is the disease-specific survival at age x. Dashed red lines indicate the median age at disease onset. Age at onset distribution if fitted with a two parameters logistic function (see Supplementary Information 2.2). FAO is defined as the age at which 1% of SALOD carrier have develop the disease (1-L^d(x) = 0.01 and setting 1-L^d(x < FAO) = 0). d, Coefficient of selection s as a function of MAO and FAO. Levels of grey indicate relation of selection to drift. Above s = 2.5e-02 (darker grey) selection is expected in all human populations (all of them having Ne > 100). Below s = 2.5e-04, alleles are neutral in most human populations (for which Ne < 10,000). In between selection levels of selection will vary of ‘small’ (dark grey) or large ‘Ne’ (light grey). Allele is rare, autosomal, dominant, disease in both sexes and penetrance is complete.