Using metabolite profiling to construct and validate a metabolite risk score for predicting future weight gain

Autoři: Nina Geidenstam aff001;  Yu-Han H. Hsu aff002;  Christina M. Astley aff003;  Josep M. Mercader aff004;  Martin Ridderstråle aff001;  Maria E. Gonzalez aff006;  Clicerio Gonzalez aff006;  Joel N. Hirschhorn aff002;  Rany M. Salem aff008
Působiště autorů: Clinical Obesity, Institution of Clinical Sciences, Malmö, Lund University, Sweden aff001;  Department of Genetics, Harvard Medical School, Boston, MA, United States of America aff002;  Division of Endocrinology and Center for Basic and Translational Obesity Research, Boston Children’s Hospital, Boston, MA, United States of America aff003;  Programs in Metabolism and Medical & Population Genetics, Broad Institute of Harvard and MIT, Cambridge, MA, United States of America aff004;  Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA, United States of America aff005;  Instituto Nacional de Salud Publica, Cuernavaca, Morelos, Mexico aff006;  Centro de Estudios en Diabetes, Mexico City, Mexico aff007;  Department of Family Medicine and Public Health, UC San Diego, San Diego, CA, United States of America aff008
Vyšlo v časopise: PLoS ONE 14(9)
Kategorie: Research Article
doi: 10.1371/journal.pone.0222445



Excess weight gain throughout adulthood can lead to adverse clinical outcomes and are influenced by complex factors that are difficult to measure in free-living individuals. Metabolite profiling offers an opportunity to systematically discover new predictors for weight gain that are relatively easy to measure compared to traditional approaches.

Methods and results

Using baseline metabolite profiling data of middle-aged individuals from the Framingham Heart Study (FHS; n = 1,508), we identified 42 metabolites associated (p < 0.05) with longitudinal change in body mass index (BMI). We performed stepwise linear regression to select 8 of these metabolites to build a metabolite risk score (MRS) for predicting future weight gain. We replicated the MRS using data from the Mexico City Diabetes Study (MCDS; n = 768), in which one standard deviation increase in the MRS corresponded to ~0.03 increase in BMI (kg/m2) per year (i.e. ~0.09 kg/year for a 1.7 m adult). We observed that none of the available anthropometric, lifestyle, and glycemic variables fully account for the MRS prediction of weight gain. Surprisingly, we found the MRS to be strongly correlated with baseline insulin sensitivity in both cohorts and to be negatively predictive of T2D in MCDS. Genome-wide association study of the MRS identified 2 genome-wide (p < 5 × 10−8) and 5 suggestively (p < 1 × 10−6) significant loci, several of which have been previously linked to obesity-related phenotypes.


We have constructed and validated a generalizable MRS for future weight gain that is an independent predictor distinct from several other known risk factors. The MRS captures a composite biological picture of weight gain, perhaps hinting at the anabolic effects of preserved insulin sensitivity. Future investigation is required to assess the relationships between MRS-predicted weight gain and other obesity-related diseases.

Klíčová slova:

Anthropometry – Body Mass Index – Genetic loci – Genome-wide association studies – Insulin – Metabolites – Obesity – Weight gain


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