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| Fältnamn | Indikatorer | Metadata |
|---|---|---|
| 000 | 12913naa a22029653a 4500 | |
| 001 | 22159059 | |
| 003 | SE-LIBR | |
| 005 | 20171221151635.0 | |
| 007 | cr|||||||||||| | |
| 008 | 171221s2017 sw |||| o |||| ||eng c | |
| 024 | 7 | a http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-3368272 uri |
| 024 | 7 | a urn:nbn:se:uu:diva-3368272 urn |
| 024 | 7 | a 10.1371/journal.pmed.10023832 doi |
| 040 | a S | |
| 041 | 0 | a eng |
| 042 | 9 EPLK | |
| 100 | 1 | a Wheeler, Eleanor4 aut |
| 245 | 1 0 | a Impact of common genetic determinants of Hemoglobin A1c on type 2 diabetes risk and diagnosis in ancestrally diverse populationsh [Elektronisk resurs]b A transethnic genome-wide meta-analysis |
| 260 | b PUBLIC LIBRARY SCIENCEc 2017 | |
| 500 | a Published | |
| 506 | 0 | a gratis |
| 520 | a Background: Glycated hemoglobin (HbA1c) is used to diagnose type 2 diabetes (T2D) and assess glycemic control in patients with diabetes. Previous genome-wide association studies (GWAS) have identified 18 HbA1c-associated genetic variants. These variants proved to be classifiable by their likely biological action as erythrocytic (also associated with erythrocyte traits) or glycemic (associated with other glucose-related traits). In this study, we tested the hypotheses that, in a very large scale GWAS, we would identify more genetic variants associated with HbA1c and that HbA1c variants implicated in erythrocytic biology would affect the diagnostic accuracy of HbA1c. We therefore expanded the number of HbA1c-associated loci and tested the effect of genetic risk-scores comprised of erythrocytic or glycemic variants on incident diabetes prediction and on prevalent diabetes screening performance. Throughout this multiancestry study, we kept a focus on interancestry differences in HbA1c genetics performance that might influence race-ancestry differences in health outcomes. Methods & findings: Using genome-wide association meta-analyses in up to 159,940 individuals from 82 cohorts of European, African, East Asian, and South Asian ancestry, we identified 60 common genetic variants associated with HbA1c. We classified variants as implicated in glycemic, erythrocytic, or unclassified biology and tested whether additive genetic scores of erythrocytic variants (GS-E) or glycemic variants (GS-G) were associated with higher T2D incidence in multiethnic longitudinal cohorts (N = 33,241). Nineteen glycemic and 22 erythrocytic variants were associated with HbA1c at genome-wide significance. GS-G was associated with higher T2D risk (incidence OR = 1.05, 95% CI 1.04-1.06, per HbA1c-raising allele, p = 3 x 10-29); whereas GS-E was not (OR = 1.00, 95% CI 0.99-1.01, p = 0.60). In Europeans and Asians, erythrocytic variants in aggregate had only modest effects on the diagnostic accuracy of HbA1c. Yet, in African Americans, the X-linked G6PD G202A variant (T-allele frequency 11%) was associated with an absolute decrease in HbA1c of 0.81%-units (95% CI 0.66-0.96) per allele in hemizygous men, and 0.68%-units (95% CI 0.38-0.97) in homozygous women. The G6PD variant may cause approximately 2% (N = 0.65 million, 95% CI0.55-0.74) of African American adults with T2Dto remain undiagnosed when screened with HbA1c. Limitations include the smaller sample sizes for non-European ancestries and the inability to classify approximately one-third of the variants. Further studies in large multiethnic cohorts with HbA1c, glycemic, and erythrocytic traits are required to better determine the biological action of the unclassified variants. Conclusions: As G6PD deficiency can be clinically silent until illness strikes, we recommend investigation of the possible benefits of screening for the G6PD genotype along with using HbA1c to diagnose T2D in populations of African ancestry or groups where G6PD deficiency is common. Screening with direct glucose measurements, or genetically-informed HbA1c diagnostic thresholds in people with G6PD deficiency, may be required to avoid missed or delayed diagnoses. | |
| 650 | 7 | a Medical and Health Sciences2 hsv |
| 650 | 7 | a Medicin och hälsovetenskap2 hsv |
| 700 | 1 | a Leong, Aaron4 aut |
| 700 | 1 | a Liu, Ching-Ti4 aut |
| 700 | 1 | a Hivert, Marie-France4 aut |
| 700 | 1 | a Strawbridge, Rona J.4 aut |
| 700 | 1 | a Podmore, Clara4 aut |
| 700 | 1 | a Li, Man4 aut |
| 700 | 1 | a Yao, Jie4 aut |
| 700 | 1 | a Sim, Xueling4 aut |
| 700 | 1 | a Hong, Jaeyoung4 aut |
| 700 | 1 | a Chu, Audrey Y.4 aut |
| 700 | 1 | a Zhang, Weihua4 aut |
| 700 | 1 | a Wang, Xu4 aut |
| 700 | 1 | a Chen, Peng4 aut |
| 700 | 1 | a Maruthur, Nisa M.4 aut |
| 700 | 1 | a Porneala, Bianca C.4 aut |
| 700 | 1 | a Sharp, Stephen J.4 aut |
| 700 | 1 | a Jia, Yucheng4 aut |
| 700 | 1 | a Kabagambe, Edmond K.4 aut |
| 700 | 1 | a Chang, Li-Ching4 aut |
| 700 | 1 | a Chen, Wei-Min4 aut |
| 700 | 1 | a Elks, Cathy E.4 aut |
| 700 | 1 | a Evans, Daniel S.4 aut |
| 700 | 1 | a Fan, Qiao4 aut |
| 700 | 1 | a Giulianini, Franco4 aut |
| 700 | 1 | a Go, Min Jin4 aut |
| 700 | 1 | a Hottenga, Jouke-Jan4 aut |
| 700 | 1 | a Hu, Yao4 aut |
| 700 | 1 | a Jackson, Anne U.4 aut |
| 700 | 1 | a Kanoni, Stavroula4 aut |
| 700 | 1 | a Kim, Young Jin4 aut |
| 700 | 1 | a Kleber, Marcus E.4 aut |
| 700 | 1 | a Ladenvall, Claes4 aut |
| 700 | 1 | a Lecoeur, Cecile4 aut |
| 700 | 1 | a Lim, Sing-Hui4 aut |
| 700 | 1 | a Lu, Yingchang4 aut |
| 700 | 1 | a Mahajan, Anubha4 aut |
| 700 | 1 | a Marzi, Carola4 aut |
| 700 | 1 | a Nalls, Mike A.4 aut |
| 700 | 1 | a Navarro, Pau4 aut |
| 700 | 1 | a Nolte, Ilja M.4 aut |
| 700 | 1 | a Rose, Lynda M.4 aut |
| 700 | 1 | a Rybin, Denis V.4 aut |
| 700 | 1 | a Sanna, Serena4 aut |
| 700 | 1 | a Shi, Yuan4 aut |
| 700 | 1 | a Stram, Daniel O.4 aut |
| 700 | 1 | a Takeuchi, Fumihiko4 aut |
| 700 | 1 | a Tan, Shu Pei4 aut |
| 700 | 1 | a van der Most, Peter J.4 aut |
| 700 | 1 | a Van Vliet-Ostaptchouk, Jana V.4 aut |
| 700 | 1 | a Wong, Andrew4 aut |
| 700 | 1 | a Yengo, Loic4 aut |
| 700 | 1 | a Zhao, Wanting4 aut |
| 700 | 1 | a Goel, Anuj4 aut |
| 700 | 1 | a Martinez Larrad, Maria Teresa4 aut |
| 700 | 1 | a Radke, Doert4 aut |
| 700 | 1 | a Salo, Perttu4 aut |
| 700 | 1 | a Tanaka, Toshiko4 aut |
| 700 | 1 | a van Iperen, Erik P. A.4 aut |
| 700 | 1 | a Abecasis, Goncalo4 aut |
| 700 | 1 | a Afaq, Saima4 aut |
| 700 | 1 | a Alizadeh, Behrooz Z.4 aut |
| 700 | 1 | a Bertoni, Alain G.4 aut |
| 700 | 1 | a Bonnefond, Amelia4 aut |
| 700 | 1 | a Boettcher, Yvonne4 aut |
| 700 | 1 | a Bottinger, Erwin P.4 aut |
| 700 | 1 | a Campbell, Harry4 aut |
| 700 | 1 | a Carlson, Olga D.4 aut |
| 700 | 1 | a Chen, Chien-Hsiun4 aut |
| 700 | 1 | a Cho, Yoon Shin4 aut |
| 700 | 1 | a Garvey, W. Timothy4 aut |
| 700 | 1 | a Gieger, Christian4 aut |
| 700 | 1 | a Goodarzi, Mark O.4 aut |
| 700 | 1 | a Grallert, Harald4 aut |
| 700 | 1 | a Hamsten, Anders4 aut |
| 700 | 1 | a Hartman, Catharina A.4 aut |
| 700 | 1 | a Herder, Christian4 aut |
| 700 | 1 | a Hsiung, Chao Agnes4 aut |
| 700 | 1 | a Huang, Jie4 aut |
| 700 | 1 | a Igase, Michiya4 aut |
| 700 | 1 | a Isono, Masato4 aut |
| 700 | 1 | a Katsuya, Tomohiro4 aut |
| 700 | 1 | a Khor, Chiea-Chuen4 aut |
| 700 | 1 | a Kiess, Wieland4 aut |
| 700 | 1 | a Kohara, Katsuhiko4 aut |
| 700 | 1 | a Kovacs, Peter4 aut |
| 700 | 1 | a Lee, Juyoung4 aut |
| 700 | 1 | a Lee, Wen-Jane4 aut |
| 700 | 1 | a Lehne, Benjamin4 aut |
| 700 | 1 | a Li, Huaixing4 aut |
| 700 | 1 | a Liu, Jianjun4 aut |
| 700 | 1 | a Lobbens, Stephane4 aut |
| 700 | 1 | a Luang, Jian'an4 aut |
| 700 | 1 | a Lyssenko, Valeriya4 aut |
| 700 | 1 | a Meitinger, Thomas4 aut |
| 700 | 1 | a Miki, Tetsuro4 aut |
| 700 | 1 | a Miljkovic, Iva4 aut |
| 700 | 1 | a Moon, Sanghoon4 aut |
| 700 | 1 | a Mulas, Antonella4 aut |
| 700 | 1 | a Mueller, Gabriele4 aut |
| 700 | 1 | a Mueller-Nurasyid, Martina4 aut |
| 700 | 1 | a Nagaraja, Ramaiah4 aut |
| 700 | 1 | a Nauck, Matthias4 aut |
| 700 | 1 | a Pankow, James S.4 aut |
| 700 | 1 | a Polasek, Ozren4 aut |
| 700 | 1 | a Prokopenko, Inga4 aut |
| 700 | 1 | a Ramos, Paula S.4 aut |
| 700 | 1 | a Rasmussen-Torvik, Laura4 aut |
| 700 | 1 | a Rathmann, Wolfgang4 aut |
| 700 | 1 | a Rich, Stephen S.4 aut |
| 700 | 1 | a Robertson, Neil R.4 aut |
| 700 | 1 | a Roden, Michael4 aut |
| 700 | 1 | a Roussel, Ronan4 aut |
| 700 | 1 | a Rudan, Igor4 aut |
| 700 | 1 | a Scott, Robert A.4 aut |
| 700 | 1 | a Scott, William R.4 aut |
| 700 | 1 | a Sennblad, Bengt4 aut |
| 700 | 1 | a Siscovick, David S.4 aut |
| 700 | 1 | a Strauch, Konstantin4 aut |
| 700 | 1 | a Sun, Liang4 aut |
| 700 | 1 | a Swertz, Morris4 aut |
| 700 | 1 | a Tajuddin, Salman M.4 aut |
| 700 | 1 | a Taylor, Kent D.4 aut |
| 700 | 1 | a Teo, Yik-Ying4 aut |
| 700 | 1 | a Tham, Yih Chung4 aut |
| 700 | 1 | a Toenjes, Anke4 aut |
| 700 | 1 | a Wareham, Nicholas J.4 aut |
| 700 | 1 | a Willemsen, Gonneke4 aut |
| 700 | 1 | a Wilsgaard, Tom4 aut |
| 700 | 1 | a Hingorani, Aroon D.4 aut |
| 700 | 1 | a Egan, Josephine4 aut |
| 700 | 1 | a Ferrucci, Luigi4 aut |
| 700 | 1 | a Hovingh, G. Kees4 aut |
| 700 | 1 | a Jula, Antti4 aut |
| 700 | 1 | a Kivimaki, Mika4 aut |
| 700 | 1 | a Kumari, Meena4 aut |
| 700 | 1 | a Njolstad, Inger4 aut |
| 700 | 1 | a Palmer, Colin N. A.4 aut |
| 700 | 1 | a Serrano Rios, Manuel4 aut |
| 700 | 1 | a Stumvoll, Michael4 aut |
| 700 | 1 | a Watkins, Hugh4 aut |
| 700 | 1 | a Aung, Tin4 aut |
| 700 | 1 | a Blueher, Matthias4 aut |
| 700 | 1 | a Boehnke, Michael4 aut |
| 700 | 1 | a Boomsma, Dorret I.4 aut |
| 700 | 1 | a Bornstein, Stefan R.4 aut |
| 700 | 1 | a Chambers, John C.4 aut |
| 700 | 1 | a Chasman, Daniel I.4 aut |
| 700 | 1 | a Chen, Yii-Der Ida4 aut |
| 700 | 1 | a Chen, Yduan-Tsong4 aut |
| 700 | 1 | a Cheng, Ching-Yu4 aut |
| 700 | 1 | a Cucca, Francesco4 aut |
| 700 | 1 | a de Geus, Eco J. C.4 aut |
| 700 | 1 | a Deloukas, Panos4 aut |
| 700 | 1 | a Evans, Michele K.4 aut |
| 700 | 1 | a Fornage, Myriam4 aut |
| 700 | 1 | a Friedlander, Yechiel4 aut |
| 700 | 1 | a Froguel, Philippe4 aut |
| 700 | 1 | a Groop, Leif4 aut |
| 700 | 1 | a Gross, Myron D.4 aut |
| 700 | 1 | a Harris, Tamara B.4 aut |
| 700 | 1 | a Hayward, Caroline4 aut |
| 700 | 1 | a Heng, Chew-Kiat4 aut |
| 700 | 1 | a Ingelsson, Erikd 1975-4 aut0 264196 |
| 700 | 1 | a Kato, Norihiro4 aut |
| 700 | 1 | a Kim, Bong-Jo4 aut |
| 700 | 1 | a Koh, Woon-Puay4 aut |
| 700 | 1 | a Kooner, Jaspal S.4 aut |
| 700 | 1 | a Koerner, Antje4 aut |
| 700 | 1 | a Kuh, Diana4 aut |
| 700 | 1 | a Kuusisto, Johanna4 aut |
| 700 | 1 | a Laakso, Markku4 aut |
| 700 | 1 | a Lin, Xu4 aut |
| 700 | 1 | a Liu, Yongmei4 aut |
| 700 | 1 | a Loos, Ruth J. F.4 aut |
| 700 | 1 | a Magnusson, Patrik K. E.4 aut |
| 700 | 1 | a Maerz, Winfried4 aut |
| 700 | 1 | a McCarthy, Mark I.4 aut |
| 700 | 1 | a Oldehinkel, Albertine J.4 aut |
| 700 | 1 | a Ong, Ken K.4 aut |
| 700 | 1 | a Pedersen, Nancy L.4 aut |
| 700 | 1 | a Pereira, Mark A.4 aut |
| 700 | 1 | a Peters, Annette4 aut |
| 700 | 1 | a Ridker, Paul M.4 aut |
| 700 | 1 | a Sabanayagam, Charumathi4 aut |
| 700 | 1 | a Sale, Michele4 aut |
| 700 | 1 | a Saleheen, Danish4 aut |
| 700 | 1 | a Saltevo, Juha4 aut |
| 700 | 1 | a Schwarz, Peter E. H.4 aut |
| 700 | 1 | a Sheu, Wayne H. H.4 aut |
| 700 | 1 | a Snieder, Harold4 aut |
| 700 | 1 | a Spector, Timothy D.4 aut |
| 700 | 1 | a Tabara, Yasuharu4 aut |
| 700 | 1 | a Tuomilehto, Jaakko4 aut |
| 700 | 1 | a van Dam, Rob M.4 aut |
| 700 | 1 | a Wilson, James G.4 aut |
| 700 | 1 | a Wilson, James F.4 aut |
| 700 | 1 | a Wolffenbuttel, Bruce H. R.4 aut |
| 700 | 1 | a Wong, Tien Yin4 aut |
| 700 | 1 | a Wu, Jer-Yuarn4 aut |
| 700 | 1 | a Yuan, Jian-Min4 aut |
| 700 | 1 | a Zonderman, Alan B.4 aut |
| 700 | 1 | a Soranzo, Nicole4 aut |
| 700 | 1 | a Guo, Xiuqing4 aut |
| 700 | 1 | a Roberts, David J.4 aut |
| 700 | 1 | a Florez, Jose C.4 aut |
| 700 | 1 | a Sladek, Robert4 aut |
| 700 | 1 | a Dupuis, Josee4 aut |
| 700 | 1 | a Morris, Andrew P.4 aut |
| 700 | 1 | a Tai, E-Shyong4 aut |
| 700 | 1 | a Selvin, Elizabeth4 aut |
| 700 | 1 | a Rotter, Jerome I.4 aut |
| 700 | 1 | a Langenberg, Claudia4 aut |
| 700 | 1 | a Barroso, Ines4 aut |
| 700 | 1 | a Meigs, James B.4 aut |
| 710 | 1 2 | a Uppsala universitetb Medicinska och farmaceutiska vetenskapsområdet4 pbl |
| 710 | 1 2 | a Uppsala universitetb Science for Life Laboratory, SciLifeLab4 pbl |
| 710 | 1 2 | a Uppsala universitetb Medicinska och farmaceutiska vetenskapsområdet4 pbl |
| 772 | 1 8 | i channel recordw 19753896 |
| 773 | 0 8 | i Värdpublikationt PLoS Medicineg 14:9x 1549-1277 |
| 856 | 4 0 | u http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-336827 |
| 856 | 4 0 | u http://dx.doi.org/10.1371/journal.pmed.1002383 |
| 856 | 4 0 | u http://uu.diva-portal.org/smash/get/diva2:1168199/FULLTEXT01 |
| 841 | 5 APISa x ab 171222||0000|||||001||||||000000e 1 | |
| 024 | 7 | 5 APISa urn:nbn:se:uu:diva-3368272 urn |
| 852 | 5 APISb APIS | |
| 856 | 4 0 | 5 APISu http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-336827 |
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