title: Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.
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.
authors.affiliation: Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA.
authors.forename: Christina L
authors.initials: CL
authors.lastname: Usher
authors.affiliation: 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.
authors.forename: Robert E
authors.identifier: 0000000231283547
authors.initials: RE
authors.lastname: Handsaker
authors.affiliation: 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.
authors.forename: Tõnu
authors.identifier: 0000000319826569
authors.initials: T
authors.lastname: Esko
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Tuke
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Michael N
authors.initials: MN
authors.lastname: Weedon
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: Alex R
authors.initials: AR
authors.lastname: Hastie
authors.affiliation: BioNano Genomics, San Diego, California, USA.
authors.forename: Han
authors.initials: H
authors.lastname: Cao
authors.affiliation: 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.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Moon
authors.affiliation: 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.
authors.forename: Seva
authors.initials: S
authors.lastname: Kashin
authors.affiliation: 1] Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. [2] Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Fuchsberger
authors.affiliation: 1] Estonian Genome Center, University of Tartu, Tartu, Estonia. [2] Institute of Molecular and Cell Biology, University of Tartu, Tartu, Estonia.
authors.forename: Andres
authors.initials: A
authors.lastname: Metspalu
authors.affiliation: Department of Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, California, USA.
authors.forename: Carlos N
authors.initials: CN
authors.lastname: Pato
authors.affiliation: Department of Psychiatry and the Behavioral Sciences, University of Southern California, Los Angeles, California, USA.
authors.forename: Michele T
authors.initials: MT
authors.lastname: Pato
authors.affiliation: 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.
authors.forename: Mark I
authors.initials: MI
authors.lastname: McCarthy
authors.affiliation: 1] Department of Biostatistics, University of Michigan, Ann Arbor, Michigan, USA. [2] Center for Statistical Genetics, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: Boehnke
authors.affiliation: 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.
authors.forename: David M
authors.identifier: 0000000272504107
authors.initials: DM
authors.lastname: Altshuler
authors.affiliation: Genetics of Complex Traits, University of Exeter Medical School, University of Exeter, Exeter, UK.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Frayling
authors.affiliation: 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.
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.affiliation: 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.
authors.forename: Steven A
authors.initials: SA
authors.lastname: McCarroll
mesh_terms: D000293:Adolescent; D000328:Adult; D000681:Amylases / Q000235:genetics*; D015992:Body Mass Index; D015331:Cohort Studies; D005260:Female; D018628:Gene Dosage; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D025341:Principal Component Analysis; D055815:Young Adult
chemical_list: D000681:Amylases