Structural forms of the human amylase locus and their relationships to SNPs, haplotypes and obesity.
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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. |
Year of Publication | 2015
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Journal | Nat Genet
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Volume | 47
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Issue | 8
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Pages | 921-5
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Date Published | 2015 Aug
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ISSN | 1546-1718
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URL | |
DOI | 10.1038/ng.3340
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PubMed ID | 26098870
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PubMed Central ID | PMC4712930
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Grant list | WT097835MF / Wellcome Trust / United Kingdom
G0500070 / Medical Research Council / United Kingdom
R56 DK062370 / DK / NIDDK NIH HHS / United States
R01 DK075787 / DK / NIDDK NIH HHS / United States
R01 DK062370 / DK / NIDDK NIH HHS / United States
R01 HG006855 / HG / NHGRI NIH HHS / United States
U01 DK062370 / DK / NIDDK NIH HHS / United States
DK062370 / DK / NIDDK NIH HHS / United States
P30 DK020572 / DK / NIDDK NIH HHS / United States
G0601261 / Medical Research Council / United Kingdom
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