To achieve adequate statistical power in our rare variant analysis, we aggregated variants into rare variant burden tests.62 We studied whole-genome sequencing (WGS) data from 4366 ALS patients and 1832 age and sex-matched controls.40,63 Rare variants were identified by population MAF <1%.41 17β-HSD1 is a dimaeric enzyme responsible for the conversion of estrone-3-sulphate into estradiol; 17β-HSD1 is encoded by the gene HSD17B1. Here, HSD17B1 is linked to amyotrophic lateral sclerosis.