ProfessorJohnChambers

Faculty of Medicine, School of Public Health

Professor of Cardiovascular Epidemiology

Contact

Location

172Medical SchoolSt Mary's Campus

Summary

My research focuses on the investigation of genetic and environmental mechanisms underlying obesity, diabetes, cardiovascular disease and related phenotypic disturbances in Indian Asians. In the last ten years I have worked closely with Professor JS Kooner (NHLI), Professor Paul Elliott (SPH), Professor James Scott (NHLI) and others, to establish the London Life Sciences Population (LOLIPOP) study, one of the largest cohort studies of Indian Asians world-wide. Our recent research efforts have capitalised on this unique population cohort, to provide new insight into the mechanisms underlying obesity, diabetes, cardiovascular disease and other human phenotypes. Key outputs include:

Identification of MLXIPL as a key determinant of plasma triglyceride levels through its function as a co-ordinator of transcriptional regulation of enzymes that channel glycolytic end-products into lipogenesis and energy storage. (Kooner et al. Nature Genetic 2008)
Showed that common genetic variants near hypothalamic receptor MC4R are associated with central obesity and insulin resistance. Risk-allele frequencies are higher amongst Indian Asians than Europeans, suggesting a possible genetic mechanism contributing to the increased burden of central adiposity and insulin resistance in Asians. (Chambers et al. Nature Genetics 2008)
Demonstrated novel association of common genetic variants in TMPRSS6 with haemoglobin levels amongst people of both European and Indian Asian ancestry, most likely mediated through alteration of protease function, and hepcidin mediated control of iron homeostasis. Our findings could provide new insight into the genetic factors influencing anaemia and related blood disorders in man (Chambers et al. Nature Genetics 2009).
Showed for the first time that that genetic variants in SCN10A influence cardiac conduction, and that genetic variation at SCN10A locus is a novel susceptibility factor for heart block and serious ventricular arrhythmia in man (Chambers et al. Nature Genetics 2010).
Used genetic association, and the concept of Mendelian randomisation, to address the key question of whether CRP is causally linked with atherosclerosis or simply a marker of underlying inflammatory disturbances in atherosclerosis (Elliott.et al. JAMA 2009)
Identifiedfour genetic loci influencing kidney function and risk of chronic kidney disease. (Chambers et al. Nature Genetics 2010).

Publications

Journals

Shih CC, Chen J, Lee AS, et al.Shih CC, Chen J, Lee AS, Bertin N, Hebrard M, Khor CC, Li Z, Juan Tan JH, Meah WY, Peh SQ, Mok SQ, Sim KS, Liu J, Wang L, Wong E, Li J, Tin A, Cheng C-Y, Heng C-K, Yuan J-M, Koh W-P, Saw SM, Friedlander Y, Sim X, Chai JF, Chong YS, Davila S, Goh LL, Lee ES, Wong TY, Karnani N, Leong KP, Yeo KK, Chambers JC, Lim SC, Goh RSM, Tan P, Dorajoo R close, 2023, A five-safes approach to a secure and scalable genomics data repository., Iscience, Vol:26

Costanzo MC, von Grotthuss M, Massung J, et al.Costanzo MC, von Grotthuss M, Massung J, Jang D, Caulkins L, Koesterer R, Gilbert C, Welch RP, Kudtarkar P, Hoang Q, Boughton AP, Singh P, Sun Y, Duby M, Moriondo A, Nguyen T, Smadbeck P, Alexander BR, Brandes M, Carmichael M, Dornbos P, Green T, Huellas-Bruskiewicz KC, Ji Y, Kluge A, McMahon AC, Mercader JM, Ruebenacker O, Sengupta S, Spalding D, Taliun D, AMP-T2D Consortium, Smith P, Thomas MK, Akolkar B, Brosnan MJ, Cherkas A, Chu AY, Fauman EB, Fox CS, Kamphaus TN, Miller MR, Nguyen L, Parsa A, Reilly DF, Ruetten H, Wholley D, Zaghloul NA, Abecasis GR, Altshuler D, Keane TM, McCarthy MI, Gaulton KJ, Florez JC, Boehnke M, Burtt NP, Flannick J close, 2023, The Type 2 Diabetes Knowledge Portal: An open access genetic resource dedicated to type 2 diabetes and related traits., Cell Metab, Vol:35, Pages:695-710.e6

Mina T, Yew YW, Ng HK, et al.Mina T, Yew YW, Ng HK, Sadhu N, Wansaicheong G, Dalan R, Low DYW, Lam BCC, Riboli E, Lee ES, Ngeow J, Elliott P, Griva K, Loh M, Lee J, Chambers J close, 2023, Adiposity impacts cognitive function in Asian populations: an epidemiological and Mendelian Randomization study., The Lancet Regional Health. Western Pacific, Vol:33, ISSN:2666-6065, Pages:1-11

Wong E, Bertin N, Hebrard M, et al.Wong E, Bertin N, Hebrard M, Tirado-Magallanes R, Bellis C, Lim WK, Chua CY, Tong PML, Chua R, Mak K, Lim TM, Cheong WY, Thien KE, Goh KT, Chai J-F, Lee J, Sung JJ-Y, Wong TY, Chin CWLD, Gluckman P, Goh LL, Ban KHK, Tan TWM, Van Dam RM, Teo YY, Loh M, Eillot P, Lee ES, Ngeow J, Riboli E, Dalan R, Kassam I, Lakshmanan LN, Lim TH, Ng HK, Mina T, Tay D, Sabanayagam C, Tham YC, Rim T, Aung T, Chee ML, Li H, Chee ML, Yeo KK, Cook SA, Pua CJ, Yang C, Chong YS, Eriksson JG, Tan KH, Yap F, Lim CW, Tsai PK, Chew WJ, Sim WC, Toh L-XG, Lin CB, Sia YY, Koh TH, Meah WY, Tan JHJ, Jeyakani J, Ow J, Ang S, Malik AJ, Kenanov D, Sim X, Cheng C-Y, Davila S, Karnani N, Leong KP, Liu J, Prabhakar S, Maurer-Stroh S, Verma CS, Krishnaswamy P, Goh RSM, Chia I, Ho C, Low D, Virabhak S, Yong J, Zheng W, Seow SW, Seck YK, Koh M, Chambers JC, Tai ES, Tan P close, 2023, The Singapore National Precision Medicine Strategy, Nature Genetics, ISSN:1061-4036

Loh M, Chambers JC, 2023, Polygenic risk scores for complex diseases: Where are we now?, Singapore Med J, Vol:64, Pages:88-89

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