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dc.contributor.authorManning A
dc.contributor.authorHighland HM
dc.contributor.authorGasser J
dc.contributor.authorSim X
dc.contributor.authorTukiainen T
dc.contributor.authorFontanillas P
dc.contributor.authorGrarup N
dc.contributor.authorRivas MA
dc.contributor.authorMahajan A
dc.contributor.authorLocke AE
dc.contributor.authorCingolani P
dc.contributor.authorPers TH
dc.contributor.authorViñuela A
dc.contributor.authorBrown AA
dc.contributor.authorWu Y
dc.contributor.authorFlannick J
dc.contributor.authorFuchsberger C
dc.contributor.authorGamazon ER
dc.contributor.authorGaulton KJ
dc.contributor.authorIm HK
dc.contributor.authorLakka Timo
dc.contributor.authorKuulasmaa Teemu
dc.contributor.authorUusitupa Matti et al.
dc.date.accessioned2017-07-13T12:42:28Z
dc.date.available2017-07-13T12:42:28Z
dc.date.issued2017
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/3480
dc.description.abstractTo identify novel coding association signals and facilitate characterization of mechanisms influencing glycemic traits and type 2 diabetes risk, we analyzed 109,215 variants derived from exome array genotyping together with an additional 390,225 variants from exome sequence in up to 39,339 normoglycemic individuals from five ancestry groups. We identified a novel association between the coding variant (p.Pro50Thr) in AKT2 and fasting plasma insulin (FI), a gene in which rare fully penetrant mutations are causal for monogenic glycemic disorders. The low-frequency allele is associated with a 12% increase in FI levels. This variant is present at 1.1% frequency in Finns but virtually absent in individuals from other ancestries. Carriers of the FI-increasing allele had increased 2-h insulin values, decreased insulin sensitivity, and increased risk of type 2 diabetes (odds ratio 1.05). In cellular studies, the AKT2-Thr50 protein exhibited a partial loss of function. We extend the allelic spectrum for coding variants in AKT2 associated with disorders of glucose homeostasis and demonstrate bidirectional effects of variants within the pleckstrin homology domain of AKT2.en
dc.language.isoENen
dc.publisherAmerican Diabetes Associationen
dc.relation.ispartofseriesDIABETES (NY)en
dc.relation.urihttps://doi.org/10.2337/db16-1329en
dc.rightsAll rights reserveden
dc.titleA Low-Frequency Inactivating AKT2 Variant Enriched in the Finnish Population Is Associated With Fasting Insulin Levels and Type 2 Diabetes Risken
dc.description.versionfinal draften
dc.contributor.departmentSchool of Medicine / Biomedicineen
dc.contributor.departmentSchool of Medicine / Clinical Nutrition,School of Medicine / Clinical Medicineen
uef.solecris.id48118385en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© American Diabetes Associationen
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP7-HEALTH/201681/EU/Novel Prep 1-Dependent Transcriptional Networks In The Control Of Insulin Sensivity/PREPOBEDIAen
dc.relation.projectidinfo:eu-repo/grantAgreement/EC/FP6-LIFESCIHEALTH/5272/EU/Health benefits of exercise: identification of genes and signalling pathways involved in effects of exercise on insulin resistance, obesity and the metabolic syndrome/EXGENESIS
dc.relation.doi10.2337/db16-1329en
dc.description.reviewstatuspeerRevieweden
dc.format.pagerange2019-2032en
dc.relation.issn0012-1797en
dc.relation.issue7en
dc.relation.volume66en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/acceptedVersionen


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