title: Complex Copy Number Variation of AMY1 does not Associate with Obesity in two East Asian Cohorts.
abstract: The human amylase gene locus at chromosome 1p21.1 is structurally complex. This region contains two pancreatic amylase genes, AMY2B, AMY2A, and a salivary gene AMY1. The AMY1 gene harbors extensive copy number variation (CNV), and recent studies have implicated this variation in adaptation to starch-rich diets and in association to obesity for European and Asian populations. In this study, we showed that by combining quantitative PCR and digital PCR, coupled with careful experimental design and calibration, we can improve the resolution of genotyping CNV with high copy numbers (CNs). In two East Asian populations of Chinese and Malay ethnicity studied, we observed a unique non-normal distribution of AMY1 diploid CN genotypes with even:odd CNs ratio of 4.5 (3.3-4.7), and an association between the common AMY2A CN = 2 genotype and odd CNs of AMY1, that could be explained by the underlying haplotypic structure. In two further case-control cohorts (n = 932 and 145, for Chinese and Malays, respectively), we did not observe the previously reported association between AMY1 and obesity or body mass index. Improved methods for accurately genotyping multiallelic CNV loci and understanding the haplotype complexity at the AMY1 locus are necessary for population genetics and association studies.
authors.affiliation: Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Rita Y Y
authors.initials: RY
authors.lastname: Yong
authors.affiliation: Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Su'Aidah B
authors.initials: SB
authors.lastname: Mustaffa
authors.affiliation: Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.
authors.forename: Pavandip S
authors.initials: PS
authors.lastname: Wasan
authors.affiliation: Unit of Biostatistics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: Liang
authors.initials: L
authors.lastname: Sheng
authors.affiliation: The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Christian R
authors.initials: CR
authors.lastname: Marshall
authors.affiliation: The Centre for Applied Genomics, Genetics and Genome Biology, The Hospital for Sick Children, Toronto, ON, Canada.|Department of Molecular Genetics and McLaughlin Centre, University of Toronto, Toronto, ON, Canada.
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Scherer
authors.affiliation: Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Department of Statistics and Applied Probability, Faculty of Science, National University of Singapore, Singapore.
authors.forename: Yik-Ying
authors.initials: YY
authors.lastname: Teo
authors.affiliation: Defence Medical and Environmental Research Institute, DSO National Laboratories, Singapore.|Saw Swee Hock School of Public Health, National University of Singapore, Singapore.|Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore.
authors.forename: Eric P H
authors.initials: EP
authors.lastname: Yap
mesh_terms: D000293:Adolescent; D044466:Asian People / Q000208:ethnology / Q000235:genetics*; D015992:Body Mass Index; D016022:Case-Control Studies; D002681:China; D056915:DNA Copy Number Variations; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D006801:Humans; D008296:Malaysia; D009765:Obesity / Q000208:ethnology / Q000235:genetics*; D055292:Pancreatic alpha-Amylases / Q000235:genetics; D016133:Polymerase Chain Reaction; D055291:Salivary alpha-Amylases / Q000235:genetics*; D055815:Young Adult
chemical_list: C524788:AMY1A protein, human; C513534:AMY2A protein, human; D055292:Pancreatic alpha-Amylases; D055291:Salivary alpha-Amylases
keywords: AMY1; AMY2A; Chinese; Malay; amylase 1; amylase 2A; copy number variation; obesity