Polygenic risk of obesity and BMI trajectories over 36 years: a longitudinal study of adult Finnish twins

Objective We investigated 36-year body mass index (BMI) trajectories in twins whose BMI in young adulthood was below, within, or above their genetically expected BMI, with a focus on twin pairs with large intrapair BMI differences (within-pair ΔBMI ≥ 3 kg/m 2 ). Methods Together, 3227 like-sexed twin pairs (34% monozygotic [MZ]) were examined at age ∼30 in 1975 and followed up in 1981, 1990, and 2011. In 1975, the observed BMI of an individual was considered either within (±2.0 kg/m 2 ), below (+2.0 kg/m 2 ) genetically expected BMI, measured by a polygenic risk score of 996,919 single nucleotide polymorphisms. Results In MZ and DZ twin pairs with large intrapair BMI differences, the co-twin with a higher observed BMI in 1975 deviated above expected BMI more frequently (∼2/3 rd ) than the co-twin with a lower BMI deviated below expectation (∼1/3 rd ). Individuals below, within, and above expectation in 1975 reached, respectively, normal weight, overweight, and obesity by 2011, with a mean BMI increase of 4.5 (95% confidence interval 4.3 to 4.8) kg/m 2 . Conclusion Categorizing BMI as below, within, or above PRS-predicted BMI helps identifying individuals who have been resistant or susceptible to weight gain. This may provide new insights into determinants and consequences of obesity.