Low copy number of the salivary amylase gene predisposes to obesity

Mario Falchi; Julie Sarah El-Sayed Moustafa; Petros Takousis; Francesco Pesce; Amélie Bonnefond; Johanna Andersson-Assarsson; Peter Sudmant; Rajkumar Dorajoo; Mashael Nedham Al-Shafai; Leonardo Bottolo; Erdal Ozdemir; Hon-Cheong So; Robert Davies; Alexandre Patrice; Robert Dent; Massimo Mangino; Pirro Hysi; Aurélie Dechaume; Marlène Huyvaert; Jane Skinner; Marie Pigeyre; Robert Caiazzo; Violeta Raverdy; Emmanuel Vaillant; Sarah Field; Beverley Balkau; Michel Marre; Sophie Visvikis-Siest; Jacques Weill; Odile Poulain-Godefroy; Peter Jacobson; Lars Sjostrom; Christopher Hammond; Panos Deloukas; Pak Chung Sham; Ruth Mcpherson; Jeannette Lee; E Shyong Tai; Robert Sladek; Lena Carlsson; Andrew Walley; Evan Eichler; François Pattou; Timothy Spector; Philippe Froguel; Sahlgrenska akademin

doi:10.1038/ng.2939

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Low copy number of the salivary amylase gene predisposes to obesity

Journal article

Peer reviewed

Low copy number of the salivary amylase gene predisposes to obesity

Mario Falchi, Julie Sarah El-Sayed Moustafa, Petros Takousis, Francesco Pesce, Amélie Bonnefond, Johanna Andersson-Assarsson, Peter Sudmant, Rajkumar Dorajoo, Mashael Nedham Al-Shafai, Leonardo Bottolo, …

Nature genetics, Vol.46(5), pp.492-497

01/05/2014

DOI: https://doi.org/10.1038/ng.2939

PMCID: PMC6485469

PMID: 24686848

Abstract

Genetics

Human genetics

Life Sciences

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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Title: Low copy number of the salivary amylase gene predisposes to obesity
Creators - without role: Mario Falchi - Genomics
Julie Sarah El-Sayed Moustafa - Genomics
Petros Takousis - Genomics
Francesco Pesce - Genomics
Amélie Bonnefond - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Johanna Andersson-Assarsson - Genomics
Peter Sudmant - University of Washington
Rajkumar Dorajoo - Genomics
Mashael Nedham Al-Shafai - Genomics
Leonardo Bottolo - Institute for Mathematical Sciences
Erdal Ozdemir - Genomics
Hon-Cheong So - City University of Hong Kong
Robert Davies - University of Ottawa
Alexandre Patrice - European Genomic Institute for Diabetes
Robert Dent - Ottawa Hospital
Massimo Mangino - King's College London
Pirro Hysi - King's College London
Aurélie Dechaume - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Marlène Huyvaert - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Jane Skinner - Norwich Medical School
Marie Pigeyre - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Robert Caiazzo - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Violeta Raverdy - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Emmanuel Vaillant - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Sarah Field - Wellcome Sanger Institute
Beverley Balkau - Epidémiologie cardiovasculaire et métabolique
Michel Marre - Service d'endocrinologie, diabétologie et nutrition [CHU Bichat]
Sophie Visvikis-Siest - Gene
Jacques Weill - Service d'endocrinologie pédiatrique [CHU Lille]
Odile Poulain-Godefroy - Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283
Peter Jacobson - University of Gothenburg
Lars Sjostrom - University of Gothenburg
Christopher Hammond - King's College London
Panos Deloukas - Wellcome Sanger Institute
Pak Chung Sham - Chinese University of Hong Kong
Ruth Mcpherson - University of Ottawa
Jeannette Lee - National University of Singapore
E Shyong Tai - National University of Singapore
Robert Sladek - Department of Human Genetics [Montréal]
Lena Carlsson - University of Gothenburg
Andrew Walley - Genomics
Evan Eichler - University of Washington
François Pattou - European Genomic Institute for Diabetes
Timothy Spector - King's College London
Philippe Froguel - Genomics
Sahlgrenska akademin
Publication Details: Nature genetics, Vol.46(5), pp.492-497
Publisher: Nature Publishing Group
Identifiers: 9938196808331
Academic Unit: King Abdulaziz University
Language: English
Resource Type: Journal article