Journal/Magazine Articles

Permanent URI for this collectionhttp://repository.kln.ac.lk/handle/123456789/13

This collection contains original research articles, review articles and case reports published in local and international peer reviewed journals by the staff members of the Faculty of Medicine

Browse

Filter results by typing the first few letters
Now showing 1 - 2 of 2
  • No Thumbnail Available
    Item
    Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study
    (The Lancet, Diabetes & Endocrinology, 2015) Chambers, J.C.; Loh, M.; Lehne, B.; Drong, A.; Kriebel, J.; Motta, V.; Wahl, S.; Elliott., H.R; Rota, F.; Scott, W.R.; Zhang, W.; Tan, S.T.; Campanella, G.; Chadeau-Hyam, M.; Yengo, L.; Richmond, R.C.; Adamowicz-Brice, M.; Afzal, U.; Bozaoglu, K.; Mok, Z.Y.; Ng, H.K.; Pattou, F.; Prokisch, H.; Rozario, M.A.; Tarantini, L.; Abbott, J.; Ala-Korpela, M.; Albetti, B.; Ammerpohl, O.; Bertazzi, P.A.; Blancher, C.; Caiazzo, R.; Danesh, J.; Gaunt, T.R.; de Lusignan, S.; Gieger, C.; Illig, T.; Jha, S.; Jones, S.; Jowett, J.; Kangas, A.J.; Kasturiratne, A.; Kato, N.; Kotea, N.; Kowlessur, S.; Pitkäniemi, J.; Punjabi, P.; Saleheen, D.; Schafmayer, C.; Soininen, P.; Tai, E.S.; Thorand, B.; Tuomilehto, J.; Wickremasinghe, A.R.; Kyrtopoulos, S.A.; Aitman, T.J.; Herder, C.; Hampe, J.; Cauchi, S.; Relton, C.L.; Froguel, P.; Soong, R.; Vineis, P.; Jarvelin, M.R.; Scott, J.; Grallert, H.; Bollati, V.; Elliott, P.; McCarthy, M.I.; Kooner, J.S. J
    BACKGROUND: Indian Asians, who make up a quarter of the world's population, are at high risk of developing type 2 diabetes. We investigated whether DNA methylation is associated with future type 2 diabetes incidence in Indian Asians and whether differences in methylation patterns between Indian Asians and Europeans are associated with, and could be used to predict, differences in the magnitude of risk of developing type 2 diabetes. METHODS: We did a nested case-control study of DNA methylation in Indian Asians and Europeans with incident type 2 diabetes who were identified from the 8-year follow-up of 25 372 participants in the London Life Sciences Prospective Population (LOLIPOP) study. Patients were recruited between May 1, 2002, and Sept 12, 2008. We did epigenome-wide association analysis using samples from Indian Asians with incident type 2 diabetes and age-matched and sex-matched Indian Asian controls, followed by replication testing of top-ranking signals in Europeans. For both discovery and replication, DNA methylation was measured in the baseline blood sample, which was collected before the onset of type 2 diabetes. Epigenome-wide significance was set at p<1 × 10(-7). We compared methylation levels between Indian Asian and European controls without type 2 diabetes at baseline to estimate the potential contribution of DNA methylation to increased risk of future type 2 diabetes incidence among Indian Asians. FINDINGS: 1608 (11•9%) of 13 535 Indian Asians and 306 (4•3%) of 7066 Europeans developed type 2 diabetes over a mean of 8•5 years (SD 1•8) of follow-up. The age-adjusted and sex-adjusted incidence of type 2 diabetes was 3•1 times (95% CI 2•8-3•6; p<0•0001) higher among Indian Asians than among Europeans, and remained 2•5 times (2•1-2•9; p<0•0001) higher after adjustment for adiposity, physical activity, family history of type 2 diabetes, and baseline glycemic measures. The mean absolute difference in methylation level between type 2 diabetes cases and controls ranged from 0•5% (SD 0•1) to 1•1% (0•2). Methylation markers at five loci were associated with future type 2 diabetes incidence; the relative risk per 1% increase in methylation was 1•09 (95% CI 1•07-1•11; p=1•3 × 10(-17)) for ABCG1, 0•94 (0•92-0•95; p=4•2 × 10(-11)) for PHOSPHO1, 0•94 (0•92-0•96; p=1•4 × 10(-9)) for SOCS3, 1•07 (1•04-1•09; p=2•1 × 10(-10)) for SREBF1, and 0•92 (0•90-0•94; p=1•2 × 10(-17)) for TXNIP. A methylation score combining results for the five loci was associated with future type 2 diabetes incidence (relative risk quartile 4 vs quartile 1 3•51, 95% CI 2•79-4•42; p=1•3 × 10(-26)), and was independent of established risk factors. Methylation score was higher among Indian Asians than Europeans (p=1 × 10(-34)). INTERPRETATION: DNA methylation might provide new insights into the pathways underlying type 2 diabetes and offer new opportunities for risk stratification and prevention of type 2 diabetes among Indian Asians. FUNDING: The European Union, the UK National Institute for Health Research, the Welcome Trust, the UK Medical Research Council, Action on Hearing Loss, the UK Biotechnology and Biological Sciences Research Council, the Oak Foundation, the Economic and Social Research Council, Helmholtz Zentrum Munchen, the German Research Center for Environmental Health, the German Federal Ministry of Education and Research, the German Center for Diabetes Research, the Munich Center for Health Sciences, the Ministry of Science and Research of the State of North Rhine-Westphalia, and the German Federal Ministry of Health. Copyright © 2015 Elsevier Ltd. All rights reserved.
  • No Thumbnail Available
    Item
    Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation
    (Nature Publishing Company, 2015) Kato, N.; Loh, M.; Takeuchi, F.; Verweij, N.; Wang, X.; Zhang, W.; Kelly, T.N.; Saleheen, D.; Lehne, B.; Leach, I.M.; Drong, A.W.; Abbott, J.; Wahl, S.; Tan, S.T.; Scott, W.R.; Campanella, G.; Chadeau-Hyam, M.; Afzal, U.; Ahluwalia, T.S.; Bonder, M.J.; Chen, P.; Dehghan, A.; Edwards, T.L.; Esko, T.; Go, M.J.; Harris, S.E.; Hartiala, J.; Kasela, S.; Kasturiratne, A.; Khor, C.C.; Kleber, M.E.; Li, H.; Mok, Z.Y.; Nakatochi, M.; Sapari, N.S.; Saxena, R.; Stewart, A.F.; Stolk, L.; Tabara, Y.; Teh, A.L.; Wu, Y.; Wu, J.Y.; Zhang, Y.; Aits, I.; Da Silva Couto Alves, A.; Das, S.; Dorajoo, R.; Hopewell, J.C.; Kim, Y.K.; Koivula, R.W.; Luan, J.; Lyytikäinen, L.P.; Nguyen, Q.N.; Pereira, M.A.; Postmus, I.; Raitakari, O.T.; Bryan, M.S.; Scott, R.A.; Sorice, R.; Tragante, V.; Traglia, M.; White, J.; Yamamoto, K.; Zhang, Y.; Adair, L.S.; Ahmed, A.; Akiyama, K.; Asif, R.; Aung, T.; Barroso, I.; Bjonnes, A.; Braun, T.R.; Cai, H.; Chang, L.C.; Chen, C.H.; Cheng, C.Y.; Chong, Y.S.; Collins, R.; Courtney, R.; Davies, G.; Delgado, G.; Do, L.D.; Doevendans, P.A.; Gansevoort, R.T.; Gao, Y.T.; Grammer, T.B.; Grarup, N.; Grewal, J.; Gu, D.; Wander, G.S.; Hartikainen, A.L.; Hazen, S.L.; He, J.; Heng, C.K.; Hixson, J.E.; Hofman, A.; Hsu, C.; Huang, W.; Husemoen, L.L.; Hwang, J.Y.; Ichihara, S.; Igase, M.; Isono, M.; Justesen, J.M.; Katsuya, T.; Kibriya, M.G.; Kim, Y.J.; Kishimoto, M.; Koh, W.P.; Kohara, K.; Kumari, M.; Kwek, K.; Lee, N.R.; Lee, J.; Liao, J.; Lieb, W.; Liewald, D.C.; Matsubara, T.; Matsushita, Y.; Meitinger, T.; Mihailov, E.; Milani, L.; Mills, R.; Mononen, N.; Müller-Nurasyid, M.; Nabika, T.; Nakashima, E.; Ng, H.K.; Nikus, K.; Nutile, T.; Ohkubo, T.; Ohnaka, K.; Parish, S.; Paternoster, L.; Peng, H.; Peters, A.; Pham, S.T.; Pinidiyapathirage, M.J.; Rahman, M.; Rakugi, H.; Rolandsson, O.; Rozario, M.A.; Ruggiero, D.; Sala, C.F.; Sarju, R.; Shimokawa, K.; Snieder, H.; Sparso, T.; Spiering, W.; Starr, J.M.; Stott, D.J.; Stram, D.O.; Sugiyama, T.; Szymczak, S.; Tang, W.H.; Tong, L.; Trompet, S.; Turjanmaa, V.; Ueshima, H.; Uitterlinden, A.G.; Umemura, S.; Vaarasmaki, M.; van Dam, R.M.; van Gilst, W.H.; van Veldhuisen, D.J.; Viikari, J.S.; Waldenberger, M.; Wang, Y.; Wang, A.; Wilson, R.; Wong, T.Y.; Xiang, Y.B.; Yamaguchi, S.; Ye, X.; Young, R.D.; Young, T.L.; Yuan, J.M.; Zhou, X.; Asselbergs, F.W.; Ciullo, M.; Clarke, R.; Deloukas, P.; Franke, A.; Franks, P.W.; Franks, S.; Friedlander, Y.; Gross, M.D.; Guo, Z.; Hansen, T.; Jarvelin, M.R.; Jorgensen, T.; Jukema, J.W.; Kähönen, M.; Kajio, H.; Kivimaki, M.; Lee, J.Y.; Lehtimäki, T.; Linneberg, A.; Miki, T.; Pedersen, O.; Samani, N.J.; Sorensen, T.I.; Takayanagi, R.; Toniolo, D.; BIOS-consortium; CARDIo GRAMplusCD; LifeLines Cohort Study; InterAct Consortium; Ahsan, H.; Allayee, H.; Chen, Y.T.; Danesh, J.; Deary, I.J.; Franco, O.H.; Franke, L.; Heijman, B.T.; Holbrook, J.D.; Isaacs, A.; Kim, B.J.; Lin, X.; Liu, J.; März, W.; Metspalu, A.; Mohlke, K.L.; Sanghera, D.K.; Shu, X.O.; van Meurs, J.B.; Vithana, E.; Wickremasinghe, A.R.; Wijmenga, C.; Wolffenbuttel, B.H.; Yokota, M.; Zheng, W.; Zhu, D.; Vineis, P.; Kyrtopoulos, S.A.; Kleinjans, J.C.; McCarthy, M.I.; Soong, R.; Gieger, C.; Scott, J.; Teo, Y.Y.; He, J.; Elliott, P.; Tai, E.S.; van der Harst, P.; Kooner, J.S.; Chambers, J.C.
    We carried out a trans-ancestry genome-wide association and replication study of blood pressurephenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10(-11) to 5.0 × 10(-21)). The sentinel blood pressure SNPs are enriched for association with DNAmethylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNAmethylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10(-6)). Our results provide new evidence for the role of DNA methylation in blood pressure regulation.