Genetic associations with temporal shifts in obesity and severe obesity during the obesity epidemic in Norway: A longitudinal population-based cohort (the HUNT Study)

• Published in: PLoS medicine 2020-12, Vol.17 (12), p.e1003452
• Main Authors: Brandkvist, Maria, Bjørngaard, Johan Håkon, Ødegård, Rønnaug Astri, Brumpton, Ben, Smith, George Davey, Åsvold, Bjørn Olav, Sund, Erik R, Kvaløy, Kirsti, Willer, Cristen J, Vie, Gunnhild Åberge
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Age; Aged; Aged, 80 and over; Analysis; Biology and Life Sciences; Body Mass Index; Demographic aspects; Development and progression; Distribution; Epidemics; Female; Gene-Environment Interaction; Genetic aspects; Genetic Association Studies; Genetic Predisposition to Disease; Genetic susceptibility; Genome-wide association studies; Genomes; Health Surveys; Heredity; Heritability; Humans; Longitudinal Studies; Male; Medicine and Health Sciences; Middle Aged; Norway; Norway - epidemiology; Obesity; Obesity - diagnosis; Obesity - epidemiology; Obesity - genetics; Overweight; Phenotype; Population; Population studies; Population-based studies; Prevalence; Risk Assessment; Risk Factors; Severity of Illness Index; Surveillance; Time Factors; Tuberculosis; Weight Gain - genetics; Young Adult
• ISSN: 1549-1676; 1549-1277; 1549-1676
• DOI: 10.1371/journal.pmed.1003452

Obesity has tripled worldwide since 1975 as environments are becoming more obesogenic. Our study investigates how changes in population weight and obesity over time are associated with genetic predisposition in the context of an obesogenic environment over 6 decades and examines the robustness of the findings using sibling design. A total of 67,110 individuals aged 13-80 years in the Nord-Trøndelag region of Norway participated with repeated standardized body mass index (BMI) measurements from 1966 to 2019 and were genotyped in a longitudinal population-based health study, the Trøndelag Health Study (the HUNT Study). Genotyping required survival to and participation in the HUNT Study in the 1990s or 2000s. Linear mixed models with observations nested within individuals were used to model the association between a genome-wide polygenic score (GPS) for BMI and BMI, while generalized estimating equations were used for obesity (BMI ≥ 30 kg/m2) and severe obesity (BMI ≥ 35 kg/m2). The increase in the average BMI and prevalence of obesity was steeper among the genetically predisposed. Among 35-year-old men, the prevalence of obesity for the least predisposed tenth increased from 0.9% (95% confidence interval [CI] 0.6% to 1.2%) to 6.5% (95% CI 5.0% to 8.0%), while the most predisposed tenth increased from 14.2% (95% CI 12.6% to 15.7%) to 39.6% (95% CI 36.1% to 43.0%). Equivalently for women of the same age, the prevalence of obesity for the least predisposed tenth increased from 1.1% (95% CI 0.7% to1.5%) to 7.6% (95% CI 6.0% to 9.2%), while the most predisposed tenth increased from 15.4% (95% CI 13.7% to 17.2%) to 42.0% (95% CI 38.7% to 45.4%). Thus, for 35-year-old men and women, respectively, the absolute change in the prevalence of obesity from 1966 to 2019 was 19.8 percentage points (95% CI 16.2 to 23.5, p < 0.0001) and 20.0 percentage points (95% CI 16.4 to 23.7, p < 0.0001) greater for the most predisposed tenth compared with the least predisposed tenth, defined using the GPS for BMI. The corresponding absolute changes in the prevalence of severe obesity for men and women, respectively, were 8.5 percentage points (95% CI 6.3 to 10.7, p < 0.0001) and 12.6 percentage points (95% CI 9.6 to 15.6, p < 0.0001) greater for the most predisposed tenth. The greater increase in BMI in genetically predisposed individuals over time was apparent after adjustment for family-level confounding using a sibling design. Key limitations include a slightly lower survival to date