Risk and polygenic scores: what an odds ratio means for one person

One variant

Risk scale

Baseline risk

Lifetime risk for someone with no copies of the risk allele. Logarithmic slider.

Effect per allele

Odds ratio or relative risk per copy. Most common-variant GWAS hits are below 1.2.

Risk alleles carried

Effect in SD units

Trait SD

For BMI in kg/m², about 4.5. rs9939609 at FTO shifts BMI about 0.10 SD per allele.

Polygenic score

Variance explained by the score

On the liability scale. Good current scores for common disease sit around 0.05 to 0.15.

Prevalence

People simulated

Transfer ratio

Portability tab. Fraction of the variance explained that survives in a population the score was not trained in.

Seed

Why scores travel badly: the weights come from a discovery population, and 80% or more of GWAS participants have been of European ancestry. Linkage disequilibrium between tag and causal variants differs by ancestry, allele frequencies differ, and effect sizes can differ, so Martin and colleagues (2019) found scores kept roughly a third to a half of their accuracy in African-ancestry samples.

One variant

Baseline risk-

Your risk-

Risk difference-

Relative risk-

People per extra case-