Publications

BibTex format

@article{Manning:2017:10.2337/db16-1329,
author = {Manning, A and Highland, HM and Gasser, J and Sim, X and Tukiainen, T and Fontanillas, P and Grarup, N and Rivas, MA and Mahajan, A and Locke, AE and Cingolani, P and Pers, TH and Viñuela, A and Brown, AA and Wu, Y and Flannick, J and Fuchsberger, C and Gamazon, ER and Gaulton, KJ and Im, HK and Teslovich, TM and Blackwell, TW and Bork-Jensen, J and Burtt, NP and Chen, Y and Green, T and Hartl, C and Kang, HM and Kumar, A and Ladenvall, C and Ma, C and Moutsianas, L and Pearson, RD and Perry, JR and Rayner, NW and Robertson, NR and Scott, LJ and van, de Bunt M and Eriksson, JG and Jula, A and Koskinen, S and Lehtimäki, T and Palotie, A and Raitakari, OT and Jacobs, SB and Wessel, J and Chu, AY and Scott, RA and Goodarzi, MO and Blancher, C and Buck, G and Buck, D and Chines, PS and Gabriel, S and Gjesing, AP and Groves, CJ and Hollensted, M and Huyghe, JR and Jackson, AU and Jun, G and Justesen, JM and Mangino, M and Murphy, J and Neville, M and Onofrio, R and Small, KS and Stringham, },
doi = {10.2337/db16-1329},
journal = {Diabetes},
pages = {2019--2032},
title = {A Low-Frequency Inactivating Akt2 Variant Enriched in the Finnish Population is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk.},
url = {http://dx.doi.org/10.2337/db16-1329},
volume = {66},
year = {2017}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - To 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 insulin, 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 fasting plasma insulin (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-hour 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.
AU  - Manning,A
AU  - Highland,HM
AU  - Gasser,J
AU  - Sim,X
AU  - Tukiainen,T
AU  - Fontanillas,P
AU  - Grarup,N
AU  - Rivas,MA
AU  - Mahajan,A
AU  - Locke,AE
AU  - Cingolani,P
AU  - Pers,TH
AU  - Viñuela,A
AU  - Brown,AA
AU  - Wu,Y
AU  - Flannick,J
AU  - Fuchsberger,C
AU  - Gamazon,ER
AU  - Gaulton,KJ
AU  - Im,HK
AU  - Teslovich,TM
AU  - Blackwell,TW
AU  - Bork-Jensen,J
AU  - Burtt,NP
AU  - Chen,Y
AU  - Green,T
AU  - Hartl,C
AU  - Kang,HM
AU  - Kumar,A
AU  - Ladenvall,C
AU  - Ma,C
AU  - Moutsianas,L
AU  - Pearson,RD
AU  - Perry,JR
AU  - Rayner,NW
AU  - Robertson,NR
AU  - Scott,LJ
AU  - van,de Bunt M
AU  - Eriksson,JG
AU  - Jula,A
AU  - Koskinen,S
AU  - Lehtimäki,T
AU  - Palotie,A
AU  - Raitakari,OT
AU  - Jacobs,SB
AU  - Wessel,J
AU  - Chu,AY
AU  - Scott,RA
AU  - Goodarzi,MO
AU  - Blancher,C
AU  - Buck,G
AU  - Buck,D
AU  - Chines,PS
AU  - Gabriel,S
AU  - Gjesing,AP
AU  - Groves,CJ
AU  - Hollensted,M
AU  - Huyghe,JR
AU  - Jackson,AU
AU  - Jun,G
AU  - Justesen,JM
AU  - Mangino,M
AU  - Murphy,J
AU  - Neville,M
AU  - Onofrio,R
AU  - Small,KS
AU  - Stringham,HM
AU  - Trakalo,J
AU  - Banks,E
AU  - Carey,J
AU  - Carneiro,MO
AU  - DePristo,M
AU  - Farjoun,Y
AU  - Fennell,T
AU  - Goldstein,JI
AU  - Grant,G
AU  - Hrabé,de Angelis M
AU  - Maguire,J
AU  - Neale,BM
AU  - Poplin,R
AU  - Purcell,S
AU  - Schwarzmayr,T
AU  - Shakir,K
AU  - Smith,JD
AU  - Strom,TM
AU  - Wieland,T
AU  - Lindstrom,J
AU  - Brandslund,I
AU  - Christensen,C
AU  - Surdulescu,GL
AU  - Lakka,TA
AU  - Doney,AS
AU  - Nilsson,P
AU  - Wareham,NJ
AU  - Langenberg,C
AU  - Varga,TV
AU  - Franks,PW
AU  - Rolandsson,O
AU  - Rosengren,AH
AU  - Farook,VS
AU  - Thameem,F
AU  - Puppala,S
AU  - Kumar,S
AU  - Lehman,DM
AU  - Jenkinson,CP
AU  - Curran,JE
AU  - Hale,DE
AU  - Fowler,SP
AU  - Arya,R
AU  - DeFronzo,RA
AU  - Abboud,HE
AU  - Syvänen,AC
AU  - Hicks,PJ
AU  - Palmer,ND
AU  - Ng,MC
AU  - Bowden,DW
AU  - Freedman,BI
AU  - Esko,T
AU  - Mägi,R
AU  - Milani,L
AU  - Mihailov,E
AU  - Metspalu,A
AU  - Narisu,N
AU  - Kinnunen,L
AU  - Bonnycastle,LL
AU  - Swift,A
AU  - Pasko,D
AU  - Wood,AR
AU  - Fadista,J
AU  - Pollin,TI
AU  - Barzilai,N
AU  - Atzmon,G
AU  - Glaser,B
AU  - Thorand,B
AU  - Strauch,K
AU  - Peters,A
AU  - Roden,M
AU  - Müller-Nurasyid,M
AU  - Liang,L
AU  - Kriebel,J
AU  - Illig,T
AU  - Grallert,H
AU  - Gieger,C
AU  - Meisinger,C
AU  - Lannfelt,L
AU  - Musani,SK
AU  - Griswold,M
AU  - Taylor,HA
AU  - Wilson,G
AU  - Correa,A
AU  - Oksa,H
AU  - Scott,WR
AU  - Afzal,U
AU  - Tan,ST
AU  - Loh,M
AU  - Chambers,JC
AU  - Sehmi,J
AU  - Kooner,JS
AU  - Lehne,B
AU  - Cho,YS
AU  - Lee,JY
AU  - Han,BG
AU  - Käräjämäki,A
AU  - Qi,Q
AU  - Qi,L
AU  - Huang,J
AU  - Hu,FB
AU  - Melander,O
AU  - Orho-Melander,M
AU  - Below,JE
AU  - Aguilar,D
AU  - Wong,TY
AU  - Liu,J
AU  - Khor,CC
AU  - Chia,KS
AU  - Lim,WY
AU  - Cheng,CY
AU  - Chan,E
AU  - Tai,ES
AU  - Aung,T
AU  - Linneberg,A
AU  - Isomaa,B
AU  - Meitinger,T
AU  - Tuomi,T
AU  - Hakaste
DO  - 10.2337/db16-1329
EP  - 2032
PY  - 2017///
SN  - 0012-1797
SP  - 2019
TI  - A Low-Frequency Inactivating Akt2 Variant Enriched in the Finnish Population is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk.
T2  - Diabetes
UR  - http://dx.doi.org/10.2337/db16-1329
UR  - http://hdl.handle.net/10044/1/46081
VL  - 66
ER  -

Download

ProfessorPhilippeFroguel

Contact

Assistant

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)