Socioeconomic disadvantage and polygenic risk for high BMI magnify obesity risk across childhood: a longitudinal, population, cohort study

Jessica A Kerr; Dorothea Dumuid; Marnie Downes; Katherine Lange; Meredith O'Connor; Lukar Thornton; Suzanne Mavoa; Kate Lycett; Tim S Olds; Ben Edwards; Justin M O'Sullivan; Markus Juonala; David Burgner; Melissa Wake

doi:10.1016/S2214-109X(23)00094-3

Socioeconomic disadvantage and polygenic risk for high BMI magnify obesity risk across childhood: a longitudinal, population, cohort study

Lancet Glob Health. 2023 Mar:11 Suppl 1:S9-S10. doi: 10.1016/S2214-109X(23)00094-3.

Authors

Affiliations

¹ Department of Psychological Medicine, University of Otago Christchurch, Christchurch, New Zealand; Population Health Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Pediatrics, University of Melbourne, Melbourne, VIC, Australia. Electronic address: jessica.kerr@otago.ac.nz.
² Alliance for Research in Exercise, University of South Australia, Adelaide, SA, Australia.
³ Population Health Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia.
⁴ Population Health Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Pediatrics, University of Melbourne, Melbourne, VIC, Australia.
⁵ Department of Marketing, University of Antwerp, Antwerp, Belgium.
⁶ Population Health Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Melbourne School of Population and Global Health, University of Melbourne, Melbourne, VIC, Australia; Environment Protection Authority Victoria, Melbourne, VIC, Australia.
⁷ Population Health Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Pediatrics, University of Melbourne, Melbourne, VIC, Australia; School of Psychology, Deakin University, Burwood, VIC, Australia.
⁸ Population Health Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Alliance for Research in Exercise, University of South Australia, Adelaide, SA, Australia.
⁹ Centre for Social Research and Methods, Australian National University, Canberra, ACT, Australia.
¹⁰ Department of Pediatrics and The Liggins Institute, University of Auckland, Auckland, New Zealand; The Maurice Wilkins Centre, University of Auckland, Auckland, New Zealand; Australian Parkinson's Mission, Garvan Institute of Medical Research, Sydney, NSW, Australia; MRC Lifecourse Epidemiology Unit, University of Southampton, Southampton, UK; Agency for Science Technology and Research, Singapore Institute for Clinical Sciences, Singapore.
¹¹ Infection and Immunity Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Medicine, University of Turku, Turku, Finland; Division of Medicine, Turku University Hospital, Turku, Finland.
¹² Infection and Immunity Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Pediatrics, University of Melbourne, Melbourne, VIC, Australia; Department of Pediatrics, Monash University, Melbourne, Australia.
¹³ Population Health Theme, Murdoch Children's Research Institute, Melbourne, VIC, Australia; Department of Pediatrics, University of Melbourne, Melbourne, VIC, Australia; Department of Pediatrics and The Liggins Institute, University of Auckland, Auckland, New Zealand.

PMID: 36866486
DOI: 10.1016/S2214-109X(23)00094-3

Abstract

Background: Across the life course, socioeconomic disadvantage disproportionately afflicts those with genetic predispositions to inflammatory diseases. We describe how socioeconomic disadvantage and polygenic risk for high BMI magnify the risk of obesity across childhood, and using causal analyses, explore the hypothetical impact of intervening on socioeconomic disadvantage to reduce adolescent obesity.

Methods: Data were drawn from a nationally representative Australian birth cohort, with biennial data collection between 2004 and 2018 (research and ethics committee approved). We generated a polygenic risk score for BMI using published genome-wide association studies. We measured early-childhood disadvantage (age 2-3 years) with a neighbourhood census-based measure and a family-level composite of parent income, occupation, and education. We used generalised linear regression (Poisson-log link) to estimate the risk of overweight or obesity (BMI ≥85th percentile) at age 14-15 years for children with early-childhood disadvantage (quintiles 4-5) versus average (quintile 3) and least disadvantage (quintiles 1-2), for those with high and low polygenic risk separately.

Findings: For 1607 children (n=796 female, n=811 male; 31% of the original cohort [N=5107]), polygenic risk and disadvantage were both associated with overweight or obesity; effects of disadvantage were more marked as polygenic risk increased. Of children with polygenic risk higher than the median (n=805), 37% of children living in disadvantage at age 2-3 years had an overweight or obese BMI by adolescence, compared with 26% of those with least disadvantage. For genetically vulnerable children, causal analyses indicated that early neighbourhood intervention to lessen disadvantage (to quintile 1-2) would reduce risk of adolescent overweight or obesity by 23% (risk ratio 0·77; 95% CI 0·57-1·04); estimates for improving family environments were similar (0·59; 0·43-0·80).

Interpretation: Actions addressing socioeconomic disadvantage could mitigate polygenic risk for developing obesity. This study benefits from population-representative longitudinal data but is limited by sample size.

Funding: Australian National Health and Medical Research Council.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Australia / epidemiology
Body Mass Index
Child
Child, Preschool
Cohort Studies
Female
Genome-Wide Association Study
Humans
Male
Overweight*
Pediatric Obesity* / epidemiology
Pediatric Obesity* / genetics
Socioeconomic Disparities in Health