Low copy number of the salivary amylase gene predisposes to obesity

Falchi, Mario, El-Sayed Moustafa, Julia Sarah, Takousis, Petros, Pesce, Francesco, Bonnefond, Amélie, Andersson-Assarsson, Johanna C., Sudmant, Peter H, Dorajoo, Rajkumar, Al-shafai, Mashael Nedham, Bottolo, Leonardo, Ozdemir, Erdal, So, Hon-cheong, Davies, Robert W, Patrice, Alexandre, Dent, Robert, Mangino, Massimo, Hysi, Pirro G., Dechaume, Aurélie, Huyvaert, Marlène, Skinner, Jane, Pigeyre, Marie, Caiazzo, Robert, Raverdy, Violeta, Vaillant, Emmanuel, Field, Sarah, Balkau, Beverley, Marre, Michel, Visvikis-Siest, Sophie, Weill, Jacques, Poulain-Godefroy, Odile, Jacobson, Peter, Sjostrom, Lars, Hammond, Christopher J, Deloukas, Panos, Sham, Pak Chung, Mcpherson, Ruth, Lee, Jeannette, Tai, E Shyong, Sladek, Robert, Carlsson, Lena M. S., Walley, Andrew, Eichler, Evan E, Pattou, Francois, Spector, Timothy D and Froguel, Philippe (2014) Low copy number of the salivary amylase gene predisposes to obesity. Nature Genetics, 46 (5). pp. 492-497. ISSN 1061-4036

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Abstract

Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts. Here we investigated the influence of gene dosage effects on adiposity through a CNV association study of gene expression levels in adipose tissue. We identified significant association of a multi-allelic CNV encompassing the salivary amylase gene (AMY1) with body mass index (BMI) and obesity, and we replicated this finding in 6,200 subjects. Increased AMY1 copy number was positively associated with both amylase gene expression (P = 2.31 × 10^−14) and serum enzyme levels (P < 2.20 × 10^−16), whereas reduced AMY1 copy number was associated with increased BMI (change in BMI per estimated copy = −0.15 (0.02) kg/m^2; P = 6.93 × 10^−10) and obesity risk (odds ratio (OR) per estimated copy = 1.19, 95% confidence interval (CI) = 1.13–1.26; P = 1.46 × 10^−10). The OR value of 1.19 per copy of AMY1 translates into about an eightfold difference in risk of obesity between subjects in the top (copy number > 9) and bottom (copy number < 4) 10% of the copy number distribution. Our study provides a first genetic link between carbohydrate metabolism and BMI and demonstrates the power of integrated genomic approaches beyond genome-wide association studies.

Item Type: Article
Uncontrolled Keywords: gene regulation,genome-wide association studies,obesity
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
Depositing User: Pure Connector
Date Deposited: 30 May 2014 20:06
Last Modified: 21 Apr 2020 23:01
URI: https://ueaeprints.uea.ac.uk/id/eprint/48526
DOI: 10.1038/ng.2939

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