Dataset Information

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

ABSTRACT:

Background

Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood.

Methods and findings

We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, range 16-39 y; 51% women; mean ± standard deviation BMI 24 ± 4 kg/m(2)). Circulating metabolites were quantified by high-throughput nuclear magnetic resonance metabolomics and biochemical assays. In cross-sectional analyses, elevated BMI was adversely associated with cardiometabolic risk markers throughout the systemic metabolite profile, including lipoprotein subclasses, fatty acid composition, amino acids, inflammatory markers, and various hormones (p<0.0005 for 68 measures). Metabolite associations with BMI were generally stronger for men than for women (median 136%, interquartile range 125%-183%). A gene score for predisposition to elevated BMI, composed of 32 established genetic correlates, was used as the instrument to assess causality. Causal effects of elevated BMI closely matched observational estimates (correspondence 87% ± 3%; R(2)= 0.89), suggesting causative influences of adiposity on the levels of numerous metabolites (p<0.0005 for 24 measures), including lipoprotein lipid subclasses and particle size, branched-chain and aromatic amino acids, and inflammation-related glycoprotein acetyls. Causal analyses of certain metabolites and potential sex differences warrant stronger statistical power. Metabolite changes associated with change in BMI during 6 y of follow-up were examined for 1,488 individuals. Change in BMI was accompanied by widespread metabolite changes, which had an association pattern similar to that of the cross-sectional observations, yet with greater metabolic effects (correspondence 160% ± 2%; R(2) = 0.92).

Conclusions

Mendelian randomization indicates causal adverse effects of increased adiposity with multiple cardiometabolic risk markers across the metabolite profile in adolescents and young adults within the non-obese weight range. Consistent with the causal influences of adiposity, weight changes were paralleled by extensive metabolic changes, suggesting a broadly modifiable systemic metabolite profile in early adulthood. Please see later in the article for the Editors' Summary.

SUBMITTER: Wurtz P

PROVIDER: S-EPMC4260795 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Publications

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

Würtz Peter P Wang Qin Q Kangas Antti J AJ Richmond Rebecca C RC Skarp Joni J Tiainen Mika M Tynkkynen Tuulia T Soininen Pasi P Havulinna Aki S AS Kaakinen Marika M Viikari Jorma S JS Savolainen Markku J MJ Kähönen Mika M Lehtimäki Terho T Männistö Satu S Blankenberg Stefan S Zeller Tanja T Laitinen Jaana J Pouta Anneli A Mäntyselkä Pekka P Vanhala Mauno M Elliott Paul P Pietiläinen Kirsi H KH Ripatti Samuli S Salomaa Veikko V Raitakari Olli T OT Järvelin Marjo-Riitta MR Smith George Davey GD Ala-Korpela Mika M

PLoS medicine 20141209 12

<h4>Background</h4>Increased adiposity is linked with higher risk for cardiometabolic diseases. We aimed to determine to what extent elevated body mass index (BMI) within the normal weight range has causal effects on the detailed systemic metabolite profile in early adulthood.<h4>Methods and findings</h4>We used Mendelian randomization to estimate causal effects of BMI on 82 metabolic measures in 12,664 adolescents and young adults from four population-based cohorts in Finland (mean age 26 y, ra ...[more]

PMID: 25490400

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Dataset Information

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

Background

Methods and findings

Conclusions

Publications

Metabolic signatures of adiposity in young adults: Mendelian randomization analysis and effects of weight change.

Similar Datasets

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