Epigenetic mechanisms such as DNA methylation plays a key role in the regulation of numerous biological processes including gene expression and cellular differentiation, with these reversible molecular processes acting as buffers of genetic variation and influencing phenotypic plasticity. Altered DNA methylation has been shown to be linked to both malignant and non-malignant complex human diseases such as cancer, diabetes and autoimmunity. Although DNA methylation profiles are now well established to display cell type and tissue specificity in human, little is known about variation in DNA methylation between ethnic populations. This inter-ethnic variation is particularly important in view of observed differences in disease risk, many of which have remained unaccounted for by traditional risk factors and genetic variation. For example, in Singapore, diabetes is most prevalent among Indians (17.2%), compared to Malays (16.6%) and Chinese (9.7%). Taking an integrative omics approach around differences in methylation profile, we aim to investigate whether differences in DNA methylation profiles account for observed differences in risk for major diseases such as T2D and CHD between ethnic populations.
As we now know in genetics, linkage disequilibrium (LD) structures vary between ethnic groups. This difference in LD has been used to refine the location of potential causal variants at loci identified by genome wide association studies (GWAS). The potential presence of differences in LD structures in methylation profiles across ethnic groups has not been previously investigated. This strategy might also be useful for refinement of methylation markers for disease risk/treatment outcome, which will prove invaluable with the increase in the number of epigenome wide association studies (EWAS) conducted in recent years.
Marie Loh is an Assistant Principal Investigator at the Translational Laboratories in Genetic Medicine at the Agency for Science, Technology and Research (A*STAR), and a Research Assistant Professor in the Department of Biochemistry at the Yong Loo Lin School of Medicine, National University of Singapore.
She holds a basic degree (BSc) in Statistics, as well as a Masters in Bioinformatics and a Masters in Statistics. She subsequently obtained her PhD from the University of Western Australin in Perth, Australia where her PhD work was focused on genetic variations between East Asians and Caucasians that influence risk and chemotherapeutic outcomes in gastrointestinal cancers. Marie Loh has also received several awards including the ASHG/Charles J. Epstein Trainee Award for Excellence in Human Genetics Research (Semifinalist) and the Young Investigator Award by the International Association for the Study of Lung Cancer (IASLC). Her current research focuses on diseases and phenotypes exhibiting ethnic differences in risk and outcome such as cardiometabolic diseases, and the role of DNA methylation in accounting for these differences.
I graduated from Multimedia University, Malaysia with B.Sc. (Hons) in Bioinformatics in 2015. My past experience as an intern at BII Singapore which involved a research project to identify the prognostic biomarkers of HCC (Hepatocellular Carcinoma Cancer) has exposed me to the analysis of genomics datasets using different kinds of bioinformatics software and computational skills. I am passionate in cancer and other complex diseases that involves high throughput omics research/analysis. I decided to join TLGM as I believe there is a lot more to explore and I also wanted to widen my research skills and knowledge. I love to sing with music and enjoy the beautiful melody and rhythm that will put you in a better mood, as well as a form of inspiration and relaxation.
Warren HR, Evangelou E, Cabrera CP, Gao H, Ren M, Mifsud B, Ntalla I, Surendran P, Liu C, Cook JP, Kraja AT, Drenos F, Loh M, Verweij N, Marten J, Karaman I, Lepe MP, O'Reilly PF, Knight J, Snieder H, Kato N, He J, Tai ES, Said MA, Porteous D, Alver M, Poulter N, Farrall M, Gansevoort RT, Padmanabhan S, Mägi R, Stanton A, Connell J, Bakker SJ, Metspalu A, Shields DC, Thom S, Brown M, Sever P, Esko T, Hayward C, van der Harst P, Saleheen D, Chowdhury R, Chambers JC, Chasman DI, Chakravarti A, Newton-Cheh C, Lindgren CM, Levy D, Kooner JS, Keavney B, Tomaszewski M, Samani NJ, Howson JM, Tobin MD, Munroe PB, Ehret GB, Wain LV; International Consortium of Blood Pressure (ICBP) 1000G Analyses.; BIOS Consortium.; Lifelines Cohort Study.; Understanding Society Scientific group.; CHD Exome+ Consortium.; ExomeBP Consortium.; T2D-GENES Consortium.; GoT2DGenes Consortium.; Cohorts for Heart and Ageing Research in Genome Epidemiology (CHARGE) BP Exome Consortium.; International Genomics of Blood Pressure (iGEN-BP) Consortium.; UK Biobank CardioMetabolic Consortium BP working group. Genome-wide association analysis identifies novel blood pressure loci and offers biological insights into cardiovascular risk. Nat Genet. 2017 Mar;49(3):403-415. doi: 10.1038/ng.3768.
11. Manning A, Highland HM, Gasser J, …, Loh M, …, McCarthy MI, Glyon AL, Lindgren CM. A Low-Frequency Inactivating Akt2 Variant Enriched in the Finnish Population is Associated With Fasting Insulin Levels and Type 2 Diabetes Risk. Diabetes. 2017 Mar 24. pii: db161329. doi: 10.2337/db16-1329.
Böger CA, Gorski M, McMahon GM, …, Loh M, …, Snieder H, Parsa A, Cohen DM. NFAT5 and SLC4A10 are genetic loci regulating plasma osmolality. JASN. 2017 Mar 30. pii: ASN.2016080892. doi: 10.1681/ASN.2016080892.
Justice AE, Winkler TW, Feitosa MF, …, Loh M, …, Borecki IB, North KE, Cupples LA. Genome-Wide Meta-Analysis of 241,258 Adults Accounting for Smoking Behavior Identifies Novel Loci for Obesity Traits. Nature Communications. 2017 Apr 26;8:14977. doi: 10.1038/ncomms14977.
Yoon-Sim Yap, MD; Li-Lian Kwok, MSc; Nicholas Syn, MD; Wen Yee Chay, MD; John Whay Kuang Chia, MD; Chee Kian Tham, MD; Nan Soon Wong, MD; Soo Kien Lo, MD; Rebecca Alexandra Dent, MD; Sili Tan, BSc; Zuan Yu Mok, BSc; King Xin Koh, MSc; Han Chong Toh, MD; Wen Hsin Koo, MD; Marie Loh, PhD; Raymond Chee Hui Ng, MD; Su Pin Choo, MD; Richie Chuan Teck Soong, PhD. Predictors of Hand-Foot Syndrome and Pyridoxine for Prevention of Capecitabine–Induced Hand-Foot Syndrome. JAMA Oncology. 2017. Accepted.
Karaman I, Ferreira D, Boulange C, Kaluarachchi M, Herrington D, Dona A, Castagné R, Moayyeri A, Lehne B, Loh M, de Vries P, Dehghan A, Franco O, Hofman A, Evangelou E, Tzoulaki I, Elliott P, Lindon J, Ebbels T. A Workflow For Integrated Processing of Multi-Cohort Untargeted NMR Metabolomics Data In Large Scale Metabolic Epidemiology. Journal of Proteome Research. 2016.
Wahl S*, Drong A*, Lehne B*, Loh M*, Scott WR*, Kunze S, Tsai P-C, Ried JS, Zhang W, Yang Y, Tan S, Fiorito G, Franke L, Guarrera S, Kasela S, Kriebel J, Richmond RC, Adamo M, Afzal U, Ala-Korpela M, Albetti B, Ammerpohl O, Apperley JF, Beekman M, Bertazzi PA, Black S.L, Blancher C, Bonder M-J, Brosch M, Carstensen-Kirberg M, De Craen AJM, de Lusignan S, Dehghan A, Elkalaawy M, Fischer K, Franco OH, Gaunt TR, Hampe J, Hashemi M, Isaacs A, Jenkinson A, Jha S, Kato N, Krogh V, Laffan M, Meisinger C, Meitinger T, Mok ZY, Motta V, Ng HK, Nikolakopoulou Z, Nteliopoulos G, Panico S, Pervjakova N, Prokisch H, Rathmann W, Roden M, Rota F, Rozario MA, Sandling JK, Schafmayer C, Schramm K, Siebert R, Slagboom PE, Soininen P, Stolk L, Strauch K, Tai E-S, Tarantini L, Thorand B, Tigchelaar EF, Tumino R, Uitterlinden AG, van Duijn C, van Meurs JBJ, Vineis P, Wickremasinghe AR, Wijmenga C, Yang T-S, Yuan W, Zhernakova A, Batterham RL, Smith GD, Deloukas P, Heijmans BT, Herder C, Hofman A, Lindgren CM, Milani L, van der Harst P, Peters A, Illig T, Relton CL, Waldenberger M, Järvelin M-R, Bollati V, Soong R, Spector TD*, Bell JT*, Scott J*, McCarthy MI*, Elliott P*, Matullo G, Gieger C*, Kooner JS*, Grallert H*, Chambers JC*. Epigenome-wide association reveals extensive perturbations in DNA methylation associated with adiposity and its adverse metabolic consequences. Nature. 2016.
Lu Y, Day FR, Gustafsson S, …, Loh M, …, Lindgren C, Kilpeläinen TO, Loos RJF. New loci for body fat percentage reveal link between adiposity and cardiometabolic disease risk. Nat Commun. 2016 Feb 1;7:10495.
Scott WR, Zhang W, Loh M, Tan ST, Lehne B, Afzal U, Peralta J, Saxena R, Ralhan S, Wander GS, Bozaoglu K, Sanghera DK, Elliott P, Scott J, Chambers JC, Kooner JS. Investigation of Genetic Variation Underlying Central Obesity amongst South Asians. PLoS One. 2016 May 19;11(5):e0155478. doi: 10.1371/journal.pone.0155478.
Lehne B, Drong AW, Loh M, Zhang W, Scott WR, Tan ST, Afzal U, Schulz R, Scott J, Jarvelin MR, Elliott P, McCarthy MI, Kooner JS, Chambers JC. Erratum to: A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies. Genome Biol. 2016 Apr 21;17:73. doi: 10.1186/s13059-016-0934-z.
Soo RA, Syn N, Lee SC, Wang L, Lim XY, Loh M, Tan SH, Zee YK, Wong AL, Chuah B, Chan D, Lim SE, Goh BC, Soong R, Yong WP. Pharmacogenetics-Guided Phase I Study of Capecitabine on an Intermittent Schedule in Patients with Advanced or Metastatic Solid Tumours. Sci Rep. 2016 Jun 14;6:27826. doi: 10.1038/srep27826.
Tan SH, Sapari NS, Miao H, Hartman M, Loh M, Chng WJ, Iau P, Buhari SA, Soong R, Lee SC. High-Throughput Mutation Profiling Changes before and 3 Weeks after Chemotherapy in Newly Diagnosed Breast Cancer Patients. PLoS One. 2015 Dec 2;10(12):e0142466.
Kato N*, Loh M*, Takeuchi F*, …, van der Harst P*, Kooner JS*, Chambers JC*. Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation. Nat Genet. 2015 Sep 21. (*: Contributed equally)
Joshi PK, Esko T, Mattsson H, …, Loh M, …, Perola M, Polašek O, Wilson JF, for ROHgen. Directional dominance on stature and cognition in diverse human populations. Nature. 2015 Jul 23;523(7561):459-62.
Chambers JC*, Loh M*, Lehne B*, …, McCarthy MI*, Elliott P*, Kooner JS*. 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. Lancet Diabetes Endocrinol. 2015 Jul;3(7):526-34. (*: Contributed equally)
Chan SL, Jin S, Loh M, Brunham LR. Progress in understanding the genomic basis for adverse drug reactions: a comprehensive review and focus on the role of ethnicity. Pharmacogenomics. 2015 Jul;16(10):1161-78.
Lehne B*, Drong A*, Loh M, Zhang W, Scott WR, Tan S-T, Afzal U, Blancher C, Scott J, Jarvelin M-R, Elliott P, McCarthy MI, Kooner JS, Chambers JC. A coherent approach for analysis of the Illumina HumanMethylation450 BeadChip improves data quality and performance in epigenome-wide association studies. Genome Biol. 2015 Feb 15;16(1):37.
Mahajan A, Sim X, Ng HJ, …, on behalf of the T2D-GENES consortium and GoT2D consortium. Identification and functional characterization of G6PC2 coding variants influencing glycemic traits defines effector transcript at the G6PC2-ABCB11 locus.PLoS Genet. 2015 Jan 27;11(1):e1004876.
Sapari NS, Elahi E, Wu M, Loh M, Ng HK, Han X, Yap HL, Klemm TP, Pang B, Benoukraf T, Teo YY, Iacopetta B, Lee SC, Soong R. Feasibility of low-throughput next generation sequencing for germline DNA screening. Clin Chem. 2014 Dec;60(12):1549-57.
Chambers JC, Abbott J, Zhang W, Turro E, Scott WR, Tan S-T, Loh M, Lehne B, O'Reilly P, Gaulton KJ, Pearson RD, Li X, Lavery A, Vandrovcova J, Wass MN, Miller K, Sehmi J, Oozageer L, Kooner I, Al-Hussaini A, Afzal U, Mills R, Grewal J, Panoulas V, Lewin AM, Northwood K, Wander GS, Geoghegan F, Li Y, Wang J, Aitman TJ, McCarthy MI, Scott J, Butcher S, Elliott P, Kooner JS. The South Asian Genome. PLoS ONE 2014 Aug 12;9(8):e102645. doi: 10.1371/journal.pone.0102645.
Loh M, Liem N, Vaithilingam A, Lim PL, Sapari NS, Cheng CL, Yan B, Pang B, Salto-Tellez M, Yong WP, Iacopetta B, Soong R. DNA Methylation Subgroups and the CpG Island Methylator Phenotype in Gastric Cancer: A Comprehensive Profiling Approach. BMC Gastroenterol. 2014 Mar 28;14:55. doi: 10.1186/1471-230X-14-55.
Chong ML, Loh M, Thakkar B, Pang B, Iacopetta B, Soong R. Phosphatidylinositol-3-kinase Pathway Aberrations in Gastric and Colorectal Cancer: Meta-analysis, Co-occurrence and Ethnic Variation. Int J Cancer. 2014 Mar 1; 134(5):1232-8. doi: 10.1002/ijc.28444.
Subramaniam MM*, Loh M*, Chan JY, Liem N, Lim PL, Yong WP, Lim XY, Yeoh KG, Iacopetta B, Soong R and Salto-Tellez M. The topography of DNA methylation in the non-neoplastic colonic mucosa surrounding colorectal cancers. Mol Carcinog. 2014 Feb; 53(2):98-108. doi: 10.1002/mc.21951. (*: co-first author)
Loh M, Chua D, Yao Y, Soo RA, Garrett K, Zeps N, Platell C, Minamoto T, Kawakami K, Iacopetta B and Soong R. Can population differences in chemotherapy outcomes be inferred from differences in pharmacogenetic frequencies? The Pharmacogenomics Journal 2012 June 26. doi: 10.1038/tpj.2012.26.
Sapari NS, Loh M, Vaithilingam A and Soong R. Clinical Potential of DNA Methylation in Gastric Cancer: A Meta-Analysis. PLoS ONE 7(4):e36275. doi: 10.1371/journal.pone.0036275.
Soo RA, Kawaguchi T, Loh M, Ou S-HI, Shieh MP, Cho B-C and Soong R. Differences in outcome and toxicity between Asian and Caucasian patients with lung cancer treated with systemic therapy. Future Oncology 2012 Apr; 8(4):451-62. doi: 10.2217/fon.12.25.
Loh M and Soong R. Challenges and Pitfalls in the Introduction of Pharmacogenetics for Cancer. Ann Acad Med Singapore 2011; 40(8):369-374.
Soo RA*, Loh M*, Mok T, Ou S-HI , Cho BC, Yeo WL, Tenen DG and Soong R. Ethnic differences in survival outcome in patients with advanced stage non-small cell lung cancer- results of a meta-analysis of randomised controlled trials. Journal of Thoracic Oncology 2011 Apr 28 Jun; 6(6):1030-1038. doi: 10.1097/JTO.0b013e3182199c03. (*: co-first author)
Tan WL, Bhattacharya B, Loh M, Balasubramanian I, Akram M, Dong D, Wong L, Thakkar B, Salto-Tellez M, Soo RA, Fichtner I, Iacopetta B and Soong R. Low cytosine triphosphate synthase 2 expression renders resistance to 5-fluorouracil in colorectal cancer. Cancer Biology & Therapy 2011 Mar 15; 11(6):599-608.
Loh M, Liem N, Lim PL, Vaithilingam A, Cheng CL, Salto-Tellez M, Yong WP and Soong R. Impact of Sample Heterogeneity on Methylation Analysis. Diagnostic Molecular Pathology 2010 Dec; 19(4):243-7. doi: 10.1097/PDM.0b013e3181de4396.
Ang PW, Loh M, Liem N, Lim PL, Grieu F, Vaithilingam A, Platell C, Yong WP, Iacopetta B and Soong R. Comprehensive profiling of DNA methylation in colorectal cancer reveals subgroups with distinct clinicopathological and molecular features. BMC Cancer. 2010 May 21; 10:227. doi: 10.1186/1471-2407-10-227.
Lai KW, Koh KX, Loh M, Tada K, Subramaniam MM, Lim XY, Vaithilingam A, Salto-Tellez M, Iacopetta B, Ito Y, Soong R and the Singapore Gastric Cancer Consortium. MicroRNA-130b regulates the tumour suppressor RUNX3 in gastric cancer. Eur J Cancer. 2010 May; 46(8):1456-63. doi: 10.1016/j.ejca.2010.01.036.
Loh M, Koh KX, Yeo BH, Song CM, Chia KS, Zhu F, Yeoh KG, Hill J, Iacopetta B and Soong R. Meta-analysis of genetic polymorphisms and gastric cancer risk: Variability in associations according to race. European Journal of Cancer 2009 Sep; 45(14):2562-8. doi: 10.1016/j.ejca.2009.03.017.
Zhu F, Loh M, Hill J, Lee S, Koh KX, Lai KW, Salto-Tellez M, Iacopetta B, Yeoh KG, Soong R and the Singapore Gastric Cancer Consortium. Genetic factors associated with intestinal metaplasia in a high risk Singapore-Chinese population: a cohort study. BMC Gastroenterology. 2009 Oct 13; 9:76. doi: 10.1186/1471-230X-9-76.
Wong WC, Loh M and Eisenhaber F. On the necessity of different statistical treatment for Illumina BeadChip and Affymetrix GeneChip data and its significance for biological interpretation. Biology Direct 2008 Jun 3;3(1):23. doi: 10.1186/1745-6150-3-23.
Choong LY, Lim S, Loh M, Man X, Chen Y, Toy W, Pan M, Chen CS, Poonepalli A, Hande MP, Tan PH, Salto-Tellez M, Wong CY, Shah N, Druker BJ and Lim YP. Progressive loss of EGFR in a sub-population of breast cancers - implications in target-directed therapeutics. Molecular Cancer Therapeutics 2007 Nov;6(11):2828-42.
Tan SH, Ida H, Lau QC, Goh BC, Chieng WS, Loh M and Ito Y. Detection of Promoter Hypermethylation in Serum Samples of Cancer Patients by Methylation Specific Polymerase Chain Reaction (MSP) for Tumour Suppressor Genes Including RUNX3. Oncology Reports 2007 Nov;18(5):1225-30.
Lee BTK, Song CM, Yeo BH, Chung CW, Chan YL, Lim TT, Chua YB, Loh M, Ang NK, Vijayakumar P, Liew L, Lim J, Lim YP, Wong CH, Chuon D, Rajagopal G and Hill J. Gastric Cancer (Biomarkers) Knowledgebase (GCBKB): A Curated and Fully Integrated Knowledgebase of Putative Biomarkers Related to Gastric Cancer. Biomarker Insights 2007: 2; 135-141.
Tan SH, Ida H, Goh BC, Hsieh W, Loh M and Ito Y. Analyses of Promoter Hypermethylation for RUNX3 and other Tumor Suppressor Genes in Nasopharyngeal Carcinoma. Anticancer Research 2006; 26(6); 4287-4292.
Lau QC, Raja E, Salto-Tellez M, Liu Q, Ito K, Inoue M, Putti TC, Loh M, Ko TK, Huang C, Ito Y and Sukumar S. RUNX3 is frequently inactivated by dual mechanisms of protein mislocalization and promoter hypermethylation in breast cancer. Cancer Research 2006 Jul 1;66(13):6512-20.
Mondry A, Liu P, Loh M and Mongelli M. Z-velocity in screening for intrauterine growth restriction. Ultrasound in Obstetrics and Gynecology. 2005 Nov; 26(6):634-8.
Tan EC and Loh M. “The Singapore polymorphism/mutation database: Our experience with setting up a country-specific database” in Blood and DNA, 2006, pp51-63.
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