Body mass index is lower in asymptomatic expansion carriers but not in pathogenic variant carriers compared to gene negatives.

: To examine the relationship between body mass index (BMI) and genotype among pre-symptomatic carriers of different pathogenic variants associated with amyotrophic lateral sclerosis. : carriers, carriers, and pathogenic variant negative controls (Gene-Negatives) were included from 3 largely independent cohorts: ALS Families Project Dominantly inherited ALS and Pre-symptomatic Familial ALS (). First reported () or measured ( and ) weight and height were used to calculate BMI. Age at weight measurement, self-reported sex (male female), and highest education (high school or below college education . graduate school or above) were extracted. The associations between BMI and genotype in each cohort were examined with multivariable linear regression models, adjusted for age, sex, and education. : A total of 223 carriers, 135 carriers, and 191 Gene-Negatives were included, deriving from ( = 114, median age 46, 37% male), ( = 221, median age 46, 30% male), and ( = 214, median age 44, 39% male). Adjusting for age, sex, and education, the mean BMI of carriers was lower than Gene-Negatives by 2.4 units (95% confidence interval [CI] = 0.3-4.6,  = 0.02) in ; 2.7 units (95% CI = 0.9-4.4,  = 0.003) in ; and 1.9 units (95% CI = 0.5-4.2,  = 0.12) in . There were no significant differences in BMI between carriers and Gene-Negatives in any of the 3 cohorts. : Compared to Gene-Negatives, average BMI is lower in asymptomatic carriers across 3 cohorts while no significant difference was found between Gene-Negatives and carriers.