Figure 1 Allele frequency and effect size for ALS-associated genes Figure 1 | Allele frequency and effect size for ALS-associated genes. Certain traits and conditions, such as height, BMI and schizophrenia, are influenced by the cumulative effect of tens or hundreds of gene variants, each only contributing a small amount to overall risk. Owing to the small effect of each variant, removal of these variants from the population by natural selection is weak, and they can become common. Diseases such as cystic fibrosis or Huntington disease result from single gene mutations that greatly increase the risk of disease. Owing to their large effects, such variants tend to be removed from the population by natural selection and remain rare, unless, as is the case for cystic fibrosis, they confer some selective advantage in certain environments. Genes associated with amyotrophic lateral sclerosis (ALS) include both types, but the majority of associated variants have an intermediate effect size. In the figure, blue areas indicate genetic variants implicated in phenotypes other than ALS, and grey areas indicate genetic variants implicated in ALS, with the name of the corresponding gene listed. The x-axis shows the number of genetic variants involved in a phenotype, ranging from Mendelian (single gene variant) to polygenic (multiple gene variants). Al-Chalabi, A. et al. (2016) Gene discovery in amyotrophic lateral sclerosis: implications for clinical management Nat. Rev. Neurol. doi:10.1038/nrneurol.2016.182