Genetics Ethnic and population differences in the genetic predisposition to human obesity C. Stryjecki 1 , A. Alyass 1 and D. Meyre 1,2 1 Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON, Canada, and 2 Department of Pathology and Molecular Medicine, McMaster University, Hamilton, ON, Canada Received 10 April 2017; revised 17 June 2017; accepted 2 August 2017 Address for correspondence: Dr D Meyre, Department of Health Research Methods, Evidence, and Impact, McMaster University, Room 3205, Michael DeGroote Centre for Learning and Discovery, 1280 Main Street West, Hamilton, Ontario L8S 4K1, Canada. E-mail: meyred@mcmaster.ca Summary Obesity rates have escalated to the point of a global pandemic with varying prevalence across ethnic groups. These differences are partially explained by lifestyle factors in addition to genetic predisposition to obesity. This review provides a comprehensive examination of the ethnic differences in the genetic architecture of obesity. Using examples from evolution, heritability, admixture, monogenic and polygenic studies of obesity, we provide explanations for ethnic differences in the prevalence of obesity. The debate over definitions of race and ethnicity, the advantages and limitations of multi-ethnic studies and future directions of research are also discussed. Multi-ethnic studies have great potential to provide a better understanding of ethnic differences in the prevalence of obesity that may result in more targeted and personalized obesity treatments. Keywords: ethnic diversity, genetic susceptibility, obesity. Abbreviations: BBS, Bardet–Biedl syndrome; BMI, body mass index; CNV, copy number variants; G × E, gene × environment interaction; G × G, gene × gene inter- action; GWAS, genome wide association study; LD, linkage disequilibrium; LEP , leptin; LEPR, leptin receptor; MC4R, melanocortin 4 receptor; PCA, principal component analysis; PCSK1, proprotein/prohormone convertase 1; POMC, pro- opiomelanocortin; PWS, Prader–Willi syndrome; RAF, risk allele frequencies; snoRNAs, five small nucleolar RNAs; SNPs, single nucleotide polymorphisms; T2D, type 2 diabetes. Introduction Obesity rates have escalated to the point of a global epi- demic over the last three decades. According to the World Health Organization, approximately 600 million adults worldwide were classified as obese in 2014 (body mass index, BMI ≥ 30 kg m À2 ), while in parallel, the worldwide prevalence of childhood overweight and obesity has increased from 4.2% in 1990 to 6.7% in 2010 and is ex- pected to reach 9.1% by 2020 (1). Obesity is associated with several comorbidities including type 2 diabetes (T2D), cardiovascular disease and some forms of cancer (2). Furthermore, childhood obesity is associated with more serious health outcomes later in life (3). Ultimately, severe forms of obesity reduce life expectancy by 13 and 8 years for men and women respectively (4). Notable differences in the prevalence of obesity have been observed across diverse ethnic groups. In the USA alone, 21.8% of Caucasians, 34.8% of African Americans, 28.3% of Hispanics, 34.3% of Native Americans and 33.0% of Pacific Islanders over the age of 30 were consid- ered to be obese between 2001 and 2002 (5); in contrast, only 4.8% of Asian Americans (individuals of Chinese, Filipina, Asian Indian, Vietnamese, Korean, Japanese and other Asian ancestry) were found to be obese (5). More recently, the National Health and Nutrition Examination Survey found 30% of Caucasians, 45% of African Americans and 36.8% of Mexican American adults over the age of 20 obesity reviews doi: 10.1111/obr.12604 © 2017 World Obesity Federation Obesity Reviews 19, 62–80, January 2018