BibTex format
@article{Lagou:2023:10.1038/s41588-023-01462-3,
author = {Lagou, V and Jiang, L and Ulrich, A and Zudina, L and González, KSG and Balkhiyarova, Z and Faggian, A and Maina, JG and Chen, S and Todorov, PV and Sharapov, S and David, A and Marullo, L and Mägi, R and Rujan, R-M and Ahlqvist, E and Thorleifsson, G and Gao, and vangelou, and Benyamin, B and Scott, RA and Isaacs, A and Zhao, JH and Willems, SM and Johnson, T and Gieger, C and Grallert, H and Meisinger, C and Müller-Nurasyid, M and Strawbridge, RJ and Goel, A and Rybin, D and Albrecht, E and Jackson, AU and Stringham, HM and Corrêa, IR and Farber-Eger, E and Steinthorsdottir, V and Uitterlinden, AG and Munroe, PB and Brown, MJ and Schmidberger, J and Holmen, O and Thorand, B and Hveem, K and Wilsgaard, T and Mohlke, KL and Wang, Z and GWA-PA, Consortium and Shmeliov, A and den, Hoed M and Loos, RJF and Kratzer, W and Haenle, M and Koenig, W and Boehm, BO and Tan, TM and Tomas, A and Salem, V and Barroso, I and Tuomilehto, J and Boehnke, M and Florez, JC and Hamsten, A and Watkins, H},
doi = {10.1038/s41588-023-01462-3},
journal = {Nature Genetics},
pages = {1448--1461},
title = {GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification},
url = {http://dx.doi.org/10.1038/s41588-023-01462-3},
volume = {55},
year = {2023}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Conventional measurements of fasting and postprandial blood glucose levels investigated in genome-wide association studies (GWAS) cannot capture the effects of DNA variability on 'around the clock' glucoregulatory processes. Here we show that GWAS meta-analysis of glucose measurements under nonstandardized conditions (random glucose (RG)) in 476,326 individuals of diverse ancestries and without diabetes enables locus discovery and innovative pathophysiological observations. We discovered 120 RG loci represented by 150 distinct signals, including 13 with sex-dimorphic effects, two cross-ancestry and seven rare frequency signals. Of these, 44 loci are new for glycemic traits. Regulatory, glycosylation and metagenomic annotations highlight ileum and colon tissues, indicating an underappreciated role of the gastrointestinal tract in controlling blood glucose. Functional follow-up and molecular dynamics simulations of lower frequency coding variants in glucagon-like peptide-1 receptor (GLP1R), a type 2 diabetes treatment target, reveal that optimal selection of GLP-1R agonist therapy will benefit from tailored genetic stratification. We also provide evidence from Mendelian randomization that lung function is modulated by blood glucose and that pulmonary dysfunction is a diabetes complication. Our investigation yields new insights into the biology of glucose regulation, diabetes complications and pathways for treatment stratification.
AU - Lagou,V
AU - Jiang,L
AU - Ulrich,A
AU - Zudina,L
AU - González,KSG
AU - Balkhiyarova,Z
AU - Faggian,A
AU - Maina,JG
AU - Chen,S
AU - Todorov,PV
AU - Sharapov,S
AU - David,A
AU - Marullo,L
AU - Mägi,R
AU - Rujan,R-M
AU - Ahlqvist,E
AU - Thorleifsson,G
AU - Gao,
AU - vangelou,
AU - Benyamin,B
AU - Scott,RA
AU - Isaacs,A
AU - Zhao,JH
AU - Willems,SM
AU - Johnson,T
AU - Gieger,C
AU - Grallert,H
AU - Meisinger,C
AU - Müller-Nurasyid,M
AU - Strawbridge,RJ
AU - Goel,A
AU - Rybin,D
AU - Albrecht,E
AU - Jackson,AU
AU - Stringham,HM
AU - Corrêa,IR
AU - Farber-Eger,E
AU - Steinthorsdottir,V
AU - Uitterlinden,AG
AU - Munroe,PB
AU - Brown,MJ
AU - Schmidberger,J
AU - Holmen,O
AU - Thorand,B
AU - Hveem,K
AU - Wilsgaard,T
AU - Mohlke,KL
AU - Wang,Z
AU - GWA-PA,Consortium
AU - Shmeliov,A
AU - den,Hoed M
AU - Loos,RJF
AU - Kratzer,W
AU - Haenle,M
AU - Koenig,W
AU - Boehm,BO
AU - Tan,TM
AU - Tomas,A
AU - Salem,V
AU - Barroso,I
AU - Tuomilehto,J
AU - Boehnke,M
AU - Florez,JC
AU - Hamsten,A
AU - Watkins,H
AU - Njølstad,I
AU - Wichmann,H-E
AU - Caulfield,MJ
AU - Khaw,K-T
AU - van,Duijn CM
AU - Hofman,A
AU - Wareham,NJ
AU - Langenberg,C
AU - Whitfield,JB
AU - Martin,NG
AU - Montgomery,G
AU - Scapoli,C
AU - Tzoulaki,I
AU - Elliott,P
AU - Thorsteinsdottir,U
AU - Stefansson,K
AU - Brittain,EL
AU - McCarthy,MI
AU - Froguel,P
AU - Sexton,PM
AU - Wootten,D
AU - Groop,L
AU - Dupuis,J
AU - Meigs,JB
AU - Deganutti,G
AU - Demirkan,A
AU - Pers,TH
AU - Reynolds,CA
AU - Aulchenko,YS
AU - Kaakinen,MA
AU - Jones,B
AU - Prokopenko,I
AU - Meta-Analysis,of Glucose and Insulin-Related Traits Consortium MAGIC
DO - 10.1038/s41588-023-01462-3
EP - 1461
PY - 2023///
SN - 1061-4036
SP - 1448
TI - GWAS of random glucose in 476,326 individuals provide insights into diabetes pathophysiology, complications and treatment stratification
T2 - Nature Genetics
UR - http://dx.doi.org/10.1038/s41588-023-01462-3
UR - https://www.ncbi.nlm.nih.gov/pubmed/37679419
UR - http://hdl.handle.net/10044/1/106739
VL - 55
ER -