Genetic Predictors of Change in Waist Circumference and Waist-to-Hip Ratio With Lifestyle Intervention: The Trans-NIH Consortium for Genetics of Weight Loss Response to Lifestyle Intervention

Jeanne M. McCaffery, Department of Allied Health Sciences, University of Connecticut, Storrs, CT.
Kathleen A. Jablonski, Department of Epidemiology, The Biostatistics Center, George Washington University, Rockville, MD.
Qing Pan, Department of Epidemiology, The Biostatistics Center, George Washington University, Rockville, MD.
Arne Astrup, Healthy Weight Center, Novo Nordisk Foundation, Hellerup, Denmark.
Malene Revsbech Christiansen, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Dolores Corella, Department of Preventive Medicine and Public Health and CIBER Physiopathology of Obesity and Nutrition, University of Valencia, Valencia, Spain.
Lauren M. Corso, Department of Allied Health Sciences, University of Connecticut, Storrs, CT.
Jose C. Florez, Diabetes Unit and Center for Genomic Medicine, Massachusetts General Hospital, Boston, MA.
Paul W. Franks, Department of Clinical Sciences, Genetic and Molecular Epidemiology Unit, Lund University Diabetes Centre, Lund University, Malmö, Sweden.
Christopher Gardner, Department of Medicine, Stanford Prevention Research Center, Stanford, CA.
Torben Hansen, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Tuomas O. Kilpeläinen, Novo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
William C. Knowler, National Institute of Diabetes and Digestive and Kidney Diseases, Phoenix, AZ.
Jaana Lindström, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
Wim H. Saris, Department of Human Biology, NUTRIM, School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre, Maastricht, the Netherlands.
Thorkild I. Sørensen, Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Public Health, Section of Epidemiology, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark.
Jaakko Tuomilehto, Population Health Unit, Finnish Institute for Health and Welfare, Helsinki, Finland.
Matti Uusitupa, Institute of Public Health and Clinical Nutrition, University of Eastern Finland, Kuopio, Finland.
Rena R. Wing, Weight Control and Diabetes Research Center, The Miriam Hospital and Warren Alpert School of Medicine at Brown University, Providence, RI.
Tanya Agurs-Collins, Division of Cancer Control and Population Sciences, National Cancer Institute, Rockville, MD.

Document Type

Journal Article

Publication Date

4-1-2022

Journal

Diabetes

Volume

71

Issue

4

DOI

10.2337/db21-0741

Abstract

Genome-wide association studies have identified single nucleotide polymorphisms (SNPs) associated with waist circumference (WC) and waist-to-hip ratio (WHR) adjusted for BMI (WCadjBMI and WHRadjBMI), but it remains unclear whether these SNPs relate to change in WCadjBMI or WHRadjBMI with lifestyle intervention for weight loss. We hypothesized that polygenic scores (PS) comprised of 59 SNPs previously associated with central adiposity would predict less of a reduction in WCadjBMI or WHRadjBMI at 8-10 weeks in two lifestyle intervention trials, NUGENOB and DiOGenes, and at 1 year in five lifestyle intervention trials, Look AHEAD, Diabetes Prevention Program, Diabetes Prevention Study, DIETFITS, and PREDIMED-Plus. One-SD higher PS related to a smaller 1-year change in WCadjBMI in the lifestyle intervention arms at year 1 and thus predicted poorer response (β = 0.007; SE = 0.003; P = 0.03) among White participants overall and in White men (β = 0.01; SE = 0.004; P = 0.01). At average weight loss, this amounted to 0.20-0.28 cm per SD. No significant findings emerged in White women or African American men for the 8-10-week outcomes or for WHRadjBMI. Findings were heterogeneous in African American women. These results indicate that polygenic risk estimated from these 59 SNPs relates to change in WCadjBMI with lifestyle intervention, but the effects are small and not of sufficient magnitude to be clinically significant.

Department

Epidemiology

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