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

Author:

Berntzen Bram J.12ORCID,Palviainen Teemu1ORCID,Silventoinen Karri3ORCID,Pietiläinen Kirsi H.24ORCID,Kaprio Jaakko1ORCID

Affiliation:

1. Institute for Molecular Medicine Finland (FIMM) University of Helsinki Helsinki Finland

2. Obesity Research Unit, Research Program for Clinical and Molecular Metabolism, Faculty of Medicine University of Helsinki Helsinki Finland

3. Faculty of Social Sciences, Population Research Unit University of Helsinki Helsinki Finland

4. HealthyWeightHub, Endocrinology, Abdominal Center Helsinki University Hospital and University of Helsinki Helsinki Finland

Abstract

AbstractObjectiveThis study investigated 36‐year BMI trajectories in twins whose BMI in young adulthood was below, within, or above their genetically predicted BMI, with a focus on twin pairs with large intrapair BMI differences (within‐pair ΔBMI ≥ 3 kg/m2).MethodsTogether, 3227 like‐sexed twin pairs (34% monozygotic) were examined at age ~30 years in 1975 and followed up in 1981, 1990, and 2011. An individual's observed BMI in 1975 was considered within (±2.0), below (<−2.0), or above (>+2.0) genetically predicted BMI, measured by a polygenic risk score of 996,919 single nucleotide polymorphisms.ResultsIn monozygotic and dizygotic twin pairs with large intrapair BMI differences, the co‐twin with a higher observed BMI in 1975 deviated above predicted BMI more frequently (~2/3) than the co‐twin with a lower BMI deviated below prediction (~1/3). Individuals below, within, and above prediction in 1975 reached, respectively, normal weight, overweight, and obesity by 2011, with a mean BMI increase of 4.5 (95% CI: 4.3–4.8).ConclusionsCategorizing BMI as below, within, or above polygenic risk score‐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.

Funder

Academy of Finland

Diabetestutkimussäätiö

Helsingin Yliopisto

Jalmari ja Rauha Ahokkaan Säätiö

Novo Nordisk Fonden

Suomen Lääketieteen Säätiö

Sydäntutkimussäätiö

Broad Institute

Publisher

Wiley

Subject

Nutrition and Dietetics,Endocrinology,Endocrinology, Diabetes and Metabolism,Medicine (miscellaneous)

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