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Genetic Variation and Obesity Prior to the Era of Genome-Wide Association Studies

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The Genetics of Obesity

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Abstract

The purpose of this chapter is to present a comprehensive review of the evidence for how genetic variation contributes to common obesity (which we have chosen to define as affecting >1 % of obese individuals, likely non-syndromic in etiology, and related to diet and inactivity) in the general population prior to the era of genome wide association studies (GWAS). Twin and adoption studies demonstrate that the tendency to be obese is highly heritable, and also suggest that the cumulative effect of gene–environment interactions on body mass index (BMI) seems to increase with age. Before GWAS, one common approach to dissecting the role of genetic variability in common obesity was to investigate candidate genes. Some of the genes implicated in monogenic or syndromic obesity by traditional linkage analysis, for example, MC4R, have milder variants that appear to be important in common obesity as well. By 2004, over 600 candidate genes or chromosomal regions had been implicated in the pathogenesis of obesity, and 18 of these had multiple lines of supporting evidence. Despite this, much of the heritability in obesity remained to be explained. Next-generation sequencing technology should produce additional insights that extended these seminal investigations but despite this, much of the so-called missing heritability identified prior to the era of GWAS persists.

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  1. Division of Endocrinology and Diabetes, Children’s Hospital of Philadelphia, 34th and Civic Center Boulevard, Suite 11NW30, Philadelphia, PA, 19104, USA

    Shana E. McCormack M.D.

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    Struan F.A. Grant

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McCormack, S.E. (2014). Genetic Variation and Obesity Prior to the Era of Genome-Wide Association Studies. In: Grant, S. (eds) The Genetics of Obesity. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-8642-8_1

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