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Nat Genet. 2015 Aug;47(8):921-5. doi: 10.1038/ng.3340. Epub 2015 Jun 22.

Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.

Author information

1
Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
2
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
3
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3] Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA. [4] Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA. [5] Estonian Genome Center, University of Tartu, Tartu, Estonia.
4
Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
5
BioNano Genomics, San Diego, California, USA.
6
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3] Center for Basic and Translational Obesity Research, Boston Children's Hospital, Boston, Massachusetts, USA. [4] Division of Endocrinology, Boston Children's Hospital, Boston, Massachusetts, USA.
7
1] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [2] Stanley Center for Psychiatric Research, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA.
8
1] Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. [2] Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
9
1] Estonian Genome Center, University of Tartu, Tartu, Estonia. [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
10
Department of Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, California, USA.
11
1] Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK. [2] Oxford Centre for Diabetes, Endocrinology and Metabolism, University of Oxford, Oxford, UK. [3] Oxford National Institute for Health Research (NIHR) Biomedical Research Centre, Churchill Hospital, Headington, Oxford, UK.
12
1] Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA. [2] Program in Medical and Population Genetics, Broad Institute of MIT and Harvard, Cambridge, Massachusetts, USA. [3] Department of Molecular Biology, Massachusetts General Hospital, Boston, Massachusetts, USA.

Abstract

Hundreds of genes reside in structurally complex, poorly understood regions of the human genome. One such region contains the three amylase genes (AMY2B, AMY2A and AMY1) responsible for digesting starch into sugar. Copy number of AMY1 is reported to be the largest genomic influence on obesity, although genome-wide association studies for obesity have found this locus unremarkable. Using whole-genome sequence analysis, droplet digital PCR and genome mapping, we identified eight common structural haplotypes of the amylase locus that suggest its mutational history. We found that the AMY1 copy number in an individual's genome is generally even (rather than odd) and partially correlates with nearby SNPs, which do not associate with body mass index (BMI). We measured amylase gene copy number in 1,000 obese or lean Estonians and in 2 other cohorts totaling ∼3,500 individuals. We had 99% power to detect the lower bound of the reported effects on BMI, yet found no association.

Comment in

PMID:
26098870
PMCID:
PMC4712930
DOI:
10.1038/ng.3340
[Indexed for MEDLINE]
Free PMC Article

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