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Low copy number of the salivary amylase gene predisposes to obesity

Mario Falchi 1 Julie Sarah El-Sayed Moustafa 1 Petros Takousis 1 Francesco Pesce 1, 2 Amélie Bonnefond 3, 4, 5 Johanna Andersson-Assarsson 1, 6 Peter Sudmant 7 Rajkumar Dorajoo 1, 8 Mashael Nedham Al-Shafai 1, 9 Leonardo Bottolo 10 Erdal Ozdemir 1 Hon-Cheong So 11 Robert Davies 12 Alexandre Patrice 5, 13, 14 Robert Dent 15 Massimo Mangino 16 Pirro Hysi 16 Aurélie Dechaume 3, 5 Marlène Huyvaert 3, 5 Jane Skinner 17 Marie Pigeyre 3, 5, 14 Robert Caiazzo 3, 5, 14 Violeta Raverdy 3, 5, 14 Emmanuel Vaillant 3, 5, 14 Sarah Field 18 Beverley Balkau 19, 20 Michel Marre 21, 22 Sophie Visvikis-Siest 23 Jacques Weill 24 Odile Poulain-Godefroy 3, 5 Peter Jacobson 6 Lars Sjostrom 6 Christopher Hammond 16 Panos Deloukas 18, 25, 26 Pak Chung Sham 27 Ruth Mcpherson 12 Jeannette Lee 28 E Shyong Tai 28, 29 Robert Sladek 30, 31, 32 Lena Carlsson 6 Andrew Walley 1, 33 Evan Eichler 7, 34 François Pattou 5, 14, 13 Timothy Spector 16 Philippe Froguel 1, 3, 5, 4
Abstract : Common multi-allelic copy number variants (CNVs) appear enriched for phenotypic associations compared to their biallelic counterparts1,2,3,4. 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/m2; 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.
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Mario Falchi, Julie Sarah El-Sayed Moustafa, Petros Takousis, Francesco Pesce, Amélie Bonnefond, et al.. Low copy number of the salivary amylase gene predisposes to obesity. Nature Genetics, Nature Publishing Group, 2014, 46 (5), pp.492 - 497. ⟨10.1038/ng.2939⟩. ⟨hal-01708422⟩

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