Browsing by Author "Lee, M."

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The Ability of ICU admission to detect maternal near misses as defined by the who near-miss criteria
(Sri Lanka College of Obstetricians & Gynaecologists, 2015) Bower, G.; Dias, T.; Shanmugaraja, V.; Lee, M.; Cooper, D.; Crofton, H.; Kumarasiri, S.; Padeniya, T.
OBJECTIVE: to assess the ability of intensive care unit (ICU) admission in pregnancy, or the postpartum period, to detect cases of obstetric near-miss. METHODS: All obstetric admissions to the ICU were included retrospectively and data collected as specified by 2011 World Health Organization (WHO) guidelines on evaluating obstetrics near-misses between 2010 and 2013 in a Sri Lankan Hospital. Proportion of ICU admissions which fulfilled the WHO criteria for Severe Acute Maternal Morbidity (SAMM), maternal mortality ratio (MMR), maternal near-miss mortality ratio (MNM: MM)), and maternal near-miss ratio (MNMR) were analysed. RESULTS: A total of 9,608 live births were reported. 118 ICU admissions and four maternal deaths were analysed. MMR was 42 per 100,000. MNMR was 9.7 per 1000, and MNM: MM was 23:1. From all ICU admissions 99 cases (79.8%) met additional WHO near-miss criteria and were classified as true SAMM. Pregnancy-induced hypertensive disorders accounted for majority of ICU admissions (37.7%). Out of eight published studies from our region none of them had a MNM: MM higher than ours. CONCLUSIONS: Obstetric near-misses may be over-diagnosed if ICU admission is considered an independent inclusion criterion for SAMM. Reporting the proportion of patients admitted to ICU which are true near-miss may illustrate differing admission thresholds for a given institution.
Genetic drivers of heterogeneity in type 2 diabetes pathophysiology
(Nature Publishing Group, 2024) Suzuki, K.; Hatzikotoulas, K.; Southam, L.; Taylor, H.J.; Yin, X.; Lorenz, K.M.; Mandla, R.; Huerta-Chagoya, A.; Melloni, G.E.M.; Kanoni, S.; Rayner, N.W.; Bocher, O.; Arruda, A.L.; Sonehara, K.; Namba, S.; Namba, S.S.K.; Preuss, M.H.; Petty, L.E.; Schroeder, P.; Vanderwerff, B.; Kals, M.; Bragg. F.; Lin, K.; Guo, X.; Zhang, W.; Yao, J.; Kim, Y.J.; Graff, M.; Takeuchi, F.; Nano, J.; Lamri, A.; Nakatochi, M.; Moon, S.; Scott, R.A.; Cook, J.P.; Lee, J.J.; Pan, I.; Taliun, D.; Parra, E.J.; Chai. J.F.; Bielak, L.F.; Tabara, Y.; Hai, Y.; Thorleifsson, G.; Grarup, N.; Sofer, T.; Wuttke, M.; Sarnowski, C.; Gieger, C.; Nousome, D.; Trompet, S.; Kwak, S.H.; Long, J.; Sun, M.; Tong, L.; Chen, W.M.; Nongmaithem, S.S.; Noordam, R.; Lim, V.J.Y.; Tam, C.H.T.; Joo, Y.Y.; Chen, C.H.; Raffield, L.M.; Prins, B.P.; Nicolas, A.; Yanek, L.R.; Chen, G.; Brody, J.A.; Kabagambe, E.; An, P.; Xiang, A.H.; Choi, H.S.; Cade, B.E.; Tan, J.; Broadaway, K.A.; Williamson, A.; Kamali, Z.; Cui, J.; Thangam, M.; Adair, L.S.; Adeyemo, A.; Aguilar-Salinas, C.A.; Ahluwalia, T.S.; Anand, S.S.; Bertoni, A.; Bork-Jensen, J.; Brandslund, I.; Buchanan, T.A.; Burant, C.F.; Butterworth, A.S.; Canouil, M.; Chan, J.C.N.; Chang, L.C.; Chee, M.L.; Chen, J.; Chen, S.H.; Chen, Y.T.; Chen, Z.; Chuang, L.M.; Cushman, M.; Danesh, J.; Das, S.K.; de Silva, H.J.; Dedoussis, G.; Dimitrov, L.; Doumatey, A.P.; Du, S.; Duan, Q.; Eckardt, K.U.; Emery, L.S.; Evans, D.S.; Evans, M.K.; Fischer, K.; Floyd, J.S.; Ford, I.; Franco, O.H.; Frayling, T.M.; Freedman, B.I.; Genter, P.; Gerstein, H.C.; Giedraitis, V.; González-Villalpando, C.; González-Villalpando, M.E.; Gordon-Larsen, P.; Gross, M.; Guare, L.A.; Hackinger, S.; Hakaste, L.; Han, S.; Hattersley, A.T.; Herder, C.; Horikoshi, M.; Howard, A.; Hsueh, W.; Huang, M.; Huang, W.; Hung, Y.; Hwang, M.Y.; Hwu, C.; Ichihara, S.; Ikram, M.A.; Ingelsson, M.; Islam, M.T.; Isono, M.; Jang, H.; Jasmine, F.; Jiang, G.; Jonas, J.B.; Jørgensen, T.; Kamanu, F.K.; Kandeel, F.R.; Kasturiratne, A.; Katsuya, T.; Kaur, V.; Kawaguchi,T.; Keaton, J.M.; Kho, A.N.; Khor, C.; Kibriya, M.G.; Kim, D.; Kronenberg, F.; Kuusisto , J.; Läll, K.; Lange, L.A.; Lee, K.M.; Lee, M.; Lee, N.R.; Leong, A.; Li, L.; Li, Y.; Li-Gao, R.; Ligthart, S.; Lindgren, C.M.; Linneberg, A.; Liu, C.; Liu, J.; Locke, A.E.; Louie, T.; Luan, J.; Luk, A.O.; Luo, X.; Lv, J.; Lynch, J.A.; Lyssenko, V.; Maeda, S.; Mamakou, V.; Mansuri, S.R.; Matsuda, K.; Meitinger, T.; Melander, O.; Metspalu, A.; Mo, H.; Morris, A.D.; Moura, F.A.; Nadler, J.L.; Nalls, M.A.; Nayak, U.; Ntalla, I.; Okada, Y.; Orozco, L.; Patel, S.R.; Patil, S.; Pei, P.; Pereira, M.A.; Peters, A.; Pirie, F.J.; Polikowsky, H.G.; Porneala, B.; Prasad, G.; Rasmussen-Torvik, L.J.; Reiner, A.P.; Roden, M.; Rohde, R.; Roll, K.; Sabanayagam, C.; Sandow, K.; Sankareswaran , A.; Sattar,N.; Schönherr, S.; Shahriar, M.; Shen , B.; Shi, J.; Shin, D.M.; Shojima, N.; Smith, J.A.; So, W.Y.; Stančáková, A.; Steinthorsdottir, V.; Stilp, A.M.; Strauch, K.; Taylor, K.D.; Thorand, B.; Thorsteinsdottir, U.; Tomlinson, B.; Tran, T.C.; Tsai, F.; Tuomilehto, J.; Tusie-Luna, T.; Udler , M.S.; Valladares-Salgado, A.; Dam, R.M.V.; Klinken, J.B.V.; Varma, R.; Wacher-Rodarte, N.; Wheeler,E.; Wickremasinghe, A.R.; Dijk, K.W.V.; Witte, D.R.; Yajnik, C.S.; Yamamoto, K.; Yamamoto, K.; Yoon, K.; Yu, C.; Yuan, J.; Yusuf, S.; Zawistowski, M.; Zhang, L.; Zheng, W.; Raffel, L.J.; Igase, M.; Ipp, E.; Redline, S.; Cho, Y.S.; Lind, L.; Province, M.A.; Fornage, .M.; Hanis, C.L.; Ingelsson, E.; Zonderman, A.B.; Psaty, B.M.; Wang, Y.; Rotimi, C.N.; Becker,D.M.; Matsuda,F.; Liu, Y.; Yokota,M.; Kardia, S.L.R.; Peyser, P.A.; Pankow, J.S.; Engert, J.C.; Bonnefond, A.; Froguel, P.; Wilson, J.G.; Sheu, W.H.H.; Wu, J.; Hayes, M.G.; Ma, R.C.W.; Wong, T.; Mook-Kanamori, D.O.; Tuomi, T.; Chandak, G.R.; Collins, F.S.; Bharadwaj, D.; Paré, G.; Sale, M.M.; Ahsan, H.; Motala, A.A.; Shu , X.; Park, K.; Jukema, J.W.; Cruz, M.; Chen, Y.I.; Rich, S.S.; McKean-Cowdin, R.; Grallert, H.; Cheng, C.; Ghanbari,M.; Tai , E.; Dupuis, J.; Kato, N.; Laakso, M.; Köttgen, A.; Koh, W.; Bowden, D.W.; Palmer, C.N.A.; Kooner, J.S.; Kooperberg, C.; Liu, S.; North, K.E.; Saleheen, D.; Hansen, T.; Pedersen, O.; Wareham, N.J.; Lee, J.; Kim, B.; Millwood , I.Y.; Walters, R.G.; Stefansson, K.; Ahlqvist, E.; Goodarzi, M.O.; Mohlke, K.L.; Langenberg, C.; Haiman, C.A.; Loos, R.J.F.; Florez, J.C.; Rader, D.J.; Ritchie, M.D.; Zöllner, S.; Mägi, R.; Marston, N.A.; Ruff, C.T.; Heel , D.A.V.; Finer, S.; Denny, J.C.; Yamauchi, T.; Kadowaki, T.; Chambers, J.C.; Ng, M.C.Y.; Sim, X.; Below, J.E.; Tsao, P.S.; Chang, K.; McCarthy, M.I.; Meigs, J.B.; Mahajan, A.; Spracklen, C.N.; Mercader, J.M.; Boehnke, M.; Rotter, J.I.; Vujkovic, M.; Voight, B.F.; Morris, A.P.; Zeggini, E.
Type 2 diabetes (T2D) is a heterogeneous disease that develops through diverse pathophysiological processes1,2 and molecular mechanisms that are often specific to cell type3,4. Here, to characterize the genetic contribution to these processes across ancestry groups, we aggregate genome-wide association study data from 2,535,601 individuals (39.7% not of European ancestry), including 428,452 cases of T2D. We identify 1,289 independent association signals at genome-wide significance (P < 5 × 10-8) that map to 611 loci, of which 145 loci are, to our knowledge, previously unreported. We define eight non-overlapping clusters of T2D signals that are characterized by distinct profiles of cardiometabolic trait associations. These clusters are differentially enriched for cell-type-specific regions of open chromatin, including pancreatic islets, adipocytes, endothelial cells and enteroendocrine cells. We build cluster-specific partitioned polygenic scores5 in a further 279,552 individuals of diverse ancestry, including 30,288 cases of T2D, and test their association with T2D-related vascular outcomes. Cluster-specific partitioned polygenic scores are associated with coronary artery disease, peripheral artery disease and end-stage diabetic nephropathy across ancestry groups, highlighting the importance of obesity-related processes in the development of vascular outcomes. Our findings show the value of integrating multi-ancestry genome-wide association study data with single-cell epigenomics to disentangle the aetiological heterogeneity that drives the development and progression of T2D. This might offer a route to optimize global access to genetically informed diabetes care.
Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation
(Nature Publishing Company, New York, 2022) Mahajan, A.; Spracklen, C.N.; Zhang, W.; Ng, M.C.Y.; Petty, L.E.; Kitajima, H.; Yu, G.Z.; Rüeger, S.; Speidel, L.; Kim, Y.J.; Horikoshi, M.; Mercader, J.M .; Taliun, D.; Moon, S.; Kwak, S.H.; Robertson, N.R.; Rayner, N.W.; Loh, M.; Kim, B.; Chiou, J.; Miguel-Escalada, I.; Parolo, P.D.B.; Lin, K.; Bragg, F.; Preuss, M.H.; Takeuchi, F.; Nano, J.; Guo, X.; Lamri, A.; Nakatoch, M.; Scott, R.A.; Lee, J.J.; Huerta-Chagoya, A.; Graff, M.; Chai, J.F.; Parra, E. J.; Yao, J.; Bielak, L.F.; Tabara, Y.; Hai, Y.; Steinthorsdottir, V.; Cook, J.P.; Kals, M.; Grarup, N.; Schmidt, E.M.; Pan, I.; Sofer, T.; Wuttke, M.; Sarnowski, C.; Gieger, C.; Nousome, D.; Trompet, S.; Long, J.; Sun, M.; Tong, L.; Chen, W.M.; Ahmad, M.; Noordam, R.; Lim, V.J.Y.; Tam, C.H.T.; Joo, Y.Y.; Chen, C.H.; Raffield, L.M.; Lecoeur, C.; Prins, B.P.; Nicolas, A.; Yanek, L.R.; Chen, G.; Jensen, R.A.; Tajuddin, S.; Kabagambe, E.K.; An, P.; Xiang, A.H.; Choi, H.S.; Cade, B.E.; Tan, J.; Flanagan, J.; Abaitua, F.; Adair, L.S.; Adeyemo, A.; Aguilar-Salinas, C.A.; Akiyama, M.; Anand, S.S.; Bertoni, A.; Bian, Z.; Bork-Jensen, J.; Brandslund, I.; Brody, J.A.; Brummett, C.M.; Buchanan, T.A.; Canouil, M.; Chan, J.C.N.; Chang, L.C.; Chee, M.L.; Chen, J.; Chen, S.H.; Chen, Y.T.; Chen, Z.; Chuang, L.M.; Cushman, M.; Das, S.K.; de Silva, H.J.; Dedoussis, G.; Dimitrov, L.; Doumatey, A.P.; Du, S.; Duan, Q.; Eckardt, K.U.; Emery, L.S.; Evans, D.S.; Evans, M.K.; Fischer, K.; Floyd, J.S.; Ford, I.; Fornage, M.; Franco, O.H.; Frayling, T.M.; Freedman, B.I.; Fuchsberger, C.; Genter, P.; Gerstein, H.C.; Giedraitis, V.; Villalpando, C.G.; Villalpando, M.E.G.; Goodarzi, M.O.; Larsen, P.G.; Gorkin, D.; Gross, M.; Guo, Y.; Hackinger, S.; Han, S.; Hattersley, A.T.; Herder, C.; Howard, A.G.; Hsueh, W.; Huang, M.; Huang, W.; Hung, Y.; Hwang, M.Y.; Hwu, C.; Ichihara, S.; Ikram, M.A.; Ingelsson, M.; Islam, M.T.; Isono, M.; Jang, H.M.; Jasmine, F.; Jiang, G.; Jonas, J.B.; Jørgensen, M.E.; Jørgensen, T.; Kamatani, Y.; Kandeel, F.R.; Kasturiratne, A.; Katsuya, T.; Kaur, V.; Kawaguchi, T.; Keaton, J.M.; Kho, A.N.; Khor, C.C.; Kibriya, M.G.; Kim, D.H.; Kohara, K.; Kriebel, J.; Kronenberg, F.; Kuusisto, J.; Läll, K.; Lange, L.A.; Lee, M.; Lee, N.R.; Leong, A.; Li, L.; Li, Y.; Li-Gao, R.; Ligthart, S.; Lindgren, C.M.; Linneberg, A.; Liu, C.; Liu, J.; Locke, A.E.; Louie, T.; Luan, J.; Luk, A.O.; Luo, X.; Lv, J.; Lyssenko, V.; Mamakou, V.; Mani, K.R.; Meitinger, T.; Metspalu, A.; Morris, A.D.; Nadkarni, G.N.; Nadler, J.L.; Nalls, M.A.; Nayak, U.; Nongmaithem, S.S.; Ntalla, I.; Okada, Y.; Orozco, L.; Patel, S.R.; Pereira, M.A.; Peters, A.; Pirie, F.J.; Porneala, B.; Prasad, G.; Preissl, S.; Rasmussen-Torvik, L.J.; Reiner, A.P.; Roden, M.; Rohde, R.; Roll, K.; Sabanayagam, C.; Sander, M.; Sandow, K.; Sattar, N.; Schönherr, S.; Schurmann, C.; Shahriar, M.; Shi, J.; Shin, D.M.; Shriner, D.; Smith, J.A.; So, W.Y.; Stančáková, A.; Stilp, A.M.; Strauch, K.; Suzuki, K.; Takahashi, A.; Taylor, K.D.; Thorand, B.; Thorleifsson, G.; Thorsteinsdottir, U.; Tomlinson, B.; Torres, J.M.; Tsai, F.; Tuomilehto, J.; Tusie-Luna, T.; Udler, M.S.; Salgado, A.V.; Dam, R.M.; Klinken, J.B.; Varma, R.; Vujkovic, M.; Wacher-Rodarte, N.; Wheeler, E.; Whitsel, E.A.; Wickremasinghe, A.R.; Dijk, K.W.; Witte, D.R.; Yajnik, C.S; Yamamoto, K.; Yamauchi, T.; Yengo, L.; Yoon, K.; Yu, C.; Yuan, J.M.; Yusuf, S.; Zhang, L.; Zheng, W.; FinnGen; eMERGE Consortium; Leslie J Raffel; Igase, M.; Ipp, E.; Redline, S.; Cho, Y.S.; Lind, L.; Province, M.A.; Hanis, C.L.; Peyser, P.A.; Ingelsson, E.; Zonderman, A.B.; Psaty, B.M.; Wang, Y.; Rotimi, C.N.; Becker, D.M.; Matsuda, F.; Liu, Y.; Zeggini, E.; Yokota, M.; Rich, S.S.; Kooperberg, C.; Pankow, J.S.; Engert, J.C.; Chen, Y.I.; Froguel, P.; Wilson, J.G.; Sheu, W.H.H.; Kardia, S.L.R.; Wu, J.Y.; Hayes, M.G.; Ma, R.C.W.; Wong, T.Y.; Groop, L.; Mook-Kanamori, D.O.; Chandak, G.R.; Collins, F.S.; Bharadwaj, D.; Paré, G.; Sale, M.M.; Ahsan, H.; Motala, A.A.; Shu, X.O.; Park, K.S.; Jukema, J.W.; Cruz, M.; Cowdin, R.M.; Grallert, H.; Cheng, C.Y.; Bottinger, E.P.; Dehghan, A.; Tai, E.S.; Dupuis, J.; Kato, N.; Laakso, M.; Köttgen, A.; Koh, W.P.; Palmer, C.N.A.; Liu, S.; Abecasis, G.; Kooner, J.S.; Loos, R.J.F.; North, K.E.; Haiman, C.A.; Florez, J.C.; Saleheen, D.; Hansen, T.; Pedersen, O.; Mägi, R.; Langenberg, C.; Wareham, N.J.; Maeda, S.; Kadowaki, T.; Lee, J.; Millwood, I.Y.; Walters, R.G.; Stefansson, K.; Myers, S.R.; Ferrer, J.; Gaulton, K.J.; Meigs, J.B.; Mohlke, K.L.; Gloyn, A.L.; Bowden, D.W.; Below, J.E.; Chambers, J.C.; Sim, X.; Boehnke, M.; Rotter, J.I.; McCarthy, M.I.; Morris, A.P.
We assembled an ancestrally diverse collection of genome-wide association studies (GWAS) of type 2 diabetes (T2D) in 180,834 affected individuals and 1,159,055 controls (48.9% non-European descent) through the Diabetes Meta-Analysis of Trans-Ethnic association studies (DIAMANTE) Consortium. Multi-ancestry GWAS meta-analysis identified 237 loci attaining stringent genome-wide significance (P < 5 × 10-9), which were delineated to 338 distinct association signals. Fine-mapping of these signals was enhanced by the increased sample size and expanded population diversity of the multi-ancestry meta-analysis, which localized 54.4% of T2D associations to a single variant with >50% posterior probability. This improved fine-mapping enabled systematic assessment of candidate causal genes and molecular mechanisms through which T2D associations are mediated, laying the foundations for functional investigations. Multi-ancestry genetic risk scores enhanced transferability of T2D prediction across diverse populations. Our study provides a step toward more effective clinical translation of T2D GWAS to improve global health for all, irrespective of genetic background.