Newcastle University

Research Interests

Development of statistical methodology for detection and characterisation of genetic factors in complex disease

The main aim of my research is to develop statistical methodology to detect and characterise genetic variants contributing to common, complex diseases such as type 1 diabetes, asthma, tuberculosis, leprosy, renal and cardiovascular diseases. This research spans the realm of both linkage and association analysis, using both family (pedigree) data and data from unrelated cases and controls. Following localisation of genetic regions that contain susceptibility loci via linkage methods, for many diseases the focus of interest is now identification of causal genetic variants within those regions. In my group we use a variety of statistical methods including regression and data-mining approaches to address this question. A particular feature of our research is on the development of methods for detecting linkage or association with, and modelling the effects at, multiple disease loci simultaneously. This includes loci that may be closely linked (i.e. that map to the same chromosomal region) and that may interact epistatically with one another.

A recent focus of research in my group has been the investigation of methods that appropriately allow for missing data when performing genetic association analysis. This can include missing genotypes and missing haplotype (phase) information. We have compared a number of weighted regression and imputation approaches, and find that a multiple imputation approach performs well when applied to real and simulated case/control and family data. This method comes at the expense of some assumptions (such as Hardy-Weinberg equilibrium), and a more robust but arguably less powerful solution can be achieved for family data by use of a complex conditioning argument.

The methods developed in our group are applied to, and in part inspired by, the data and questions of interest arising from our collaborations with clinical and biological research colleagues.

Co-workers

Rebecca Darlay BSc PhD
MRC Research Associate
Kristin Ayers BS MS PhD
Wellcome Trust Research Associate
Richard Howey
Research Associate BSc PhD

• Ermini L, Goodship THJ, Strain L, Weale ME, Sacks SH, Cordell HJ, Fremeaux-Bacchi V, Sheerin NS. Common genetic variants in complement genes other than CFH, CD46 and the CFHRs are not associated with aHUS. Molecular Immunology 2012, 49(4), 640-648.
• Ueki M, Cordell HJ. Improved Statistics for Genome-Wide Interaction Analysis. PLoS Genetics 2012, 8(4), e1002625.
• Brown SJ, Kroboth K, Sandilands A, Campbell LE, Pohler E, Kezic S, Cordell HJ, McLean WHI, Irvine AD. Intragenic Copy Number Variation within Filaggrin Contributes to the Risk of Atopic Dermatitis with a Dose-Dependent Effect. Journal of Investigative Dermatology 2012, 132(1), 98-104.
• Soemedi R, Topf A, Wilson IJ, Darlay R, Rahman T, Glen E, Hall D, Huang N, Bentham J, Bhattacharya S, Cosgrove C, Brook JD, Granados-Riveron J, Setchfield K, Bu'lock F, Thornborough C, Devreindt K, Breckpot J, Hofbeck M, Lathrop M, Rauch A, Blue G, Winlaw D, Hurles M, Santibanez-Koref M, Cordell H, Goodship J, Keavney B. Phenotype-Specific Effect of Chromosome 1q21.1Rearrangements and GJA5 Duplications in 2437 CongenitalHeart Disease Patients and 6760 Controls. Human Molecular Genetics 2012, (epub ahead of print).
• Mells GF, Floyd JAB, Morley KI, Cordell HJ, Franklin CS, Shin SY, Heneghan MA, Neuberger JM, Donaldson PT, Day DB, Ducker SJ, Muriithi AW, Wheater EF, Hammond CJ, Dawwas MF, Jones DE, Peltonen L, Alexander GJ, Sandford RN, Anderson CA, The UK PBC Consortium, The Wellcome Trust Case Control Co. Genome-wide association study identifies 12 new susceptibility loci for primary biliary cirrhosis. Nature Genetics 2011, 43(4), 329-U151.
• Ainsworth HE, Unwin J, Jamison DL, Cordell HJ. Investigation of Maternal Effects, Maternal-Fetal Interactions and Parent-of-Origin Effects (Imprinting), Using Mothers and Their Offspring. Genetic Epidemiology 2011, 35(1), 19-45.
• Brown SJ, Asai Y, Cordell HJ, Campbell LE, Zhao YW, Liao HH, Northstone K, Henderson J, Alizadehfar R, Ben-Shoshan M, Morgan K, Roberts G, Masthoff LJN, Pasmans SGMA, van den Akker PC, Wijmenga C, Hourihane JO, Palmer CNA, Lack G, Clarke A, Hull PR, Irvine AD, McLean WHI. Loss-of-function variants in the filaggrin gene are a significant risk factor for peanut allergy. Journal of Allergy and Clinical Immunology 2011, 127(3), 661-667.
• Kirkwood TBL, Cordell HJ, Finch CE. Speed-bumps ahead for the genetics of later-life diseases. Trends in Genetics 2011, 27(10), 387-388.
• Hughes A, Orr N, Cordell H, Goodship T. Reply to “Associations of CFHR1–CFHR3 deletion and a CFH SNP to age-related macular degeneration are not independent”. Nature Genetics 2010, 42(7), 555-556.
• Ayers K, Cordell H. SNP Selection in genome-wide and candidate gene studies via penalized logistic regression. Genetic Epidemiology 2010, 34(8), 879-891.
• Cordell HJ, Darlay R, Charoen P, Stewart A, Gullett AM, Lambert HJ, Malcolm S, Feather SA, Goodship THJ, Woolf AS, Kenda RB, Goodship JA, UK VUR Study Grp. Whole-Genome Linkage and Association Scan in Primary, Nonsyndromic Vesicoureteric Reflux. Journal of the American Society of Nephrology 2010, 21(1), 113-123.
• Daly AK, Donaldson PT, Bhatnagar P, Shen Y, Pe'er I, Floratos A, Daly MJ, Goldstein DB, John S, Nelson MR, Graham J, Park BK, Dillon JF, Bernal W, Cordell HJ, Pirmohamed M, Aithal GP, Day CP. HLA-B*5701 genotype is a major determinant of drug-induced liver injury due to flucloxacillin. Nature Genetics 2009, 41(7), 816-819.
• Biernacka JM, Cordell HJ. A composite-likelihood approach for identifying polymorphisms that are potentially directly associated with disease. European Journal of Human Genetics 2009, 17(5), 644-650.
• Cordell HJ. Detecting gene-gene interactions that underlie human diseases. Nature Reviews Genetics 2009. MACMILLAN BUILDING, 4 CRINAN ST, LONDON N1 9XW, ENGLAND: NATURE PUBLISHING GROUP, 10(6), 392-404.
• Brown SJ, Relton CL, Liao H, Zhao Y, Sandilands A, Wilson IJ, Burn J, Reynolds NJ, McLean WH, Cordell HJ. Filaggrin loss-of-function mutations and childhood atopic eczma: a population-based case-control study. Journal of Allergy and Clinical Immunology 2008, 121(4), 940-946.e3.
• Biernacka JM, Cordell HJ. A composite likelihood approach for inference on directly associated polymorphisms. In: Genetic Epidemiology. 2007, St. Petersburg, Florida: John Wiley & Sons, Inc.
• Croiseau P, Genin E, Cordell HJ. Dealing with missing data in family-based association studies: A multiple imputation approach. Human Heredity 2007, 63(3-4), 229-238.
• Biernacka JM, Cordell HJ. Exploring causality via identification of SNPs or haplotypes responsible for a linkage signal. Genetic Epidemiology 2007, 31(7), 727-740.
• Wheeler E, Cordell HJ. Quantitative trait association in parent offspring trios: Extension of case/pseudocontrol method and comparison of prospective and retrospective approaches. Genetic Epidemiology 2007, 31(8), 813-833.
• Cordell HJ. Estimation and Testing of Genotype and Haplotype Effects in Case-Control Studies: Comparison of Weighted Regression and Multiple Imputation Procedures. Genetic Epidemiology 2006,30 3 259-275.
• Biernacka JM, Cordell HJ. Perils and pitfalls of permutation tests for distinguishing the effects of neighbouring polymorphisms. Genetic Epidemiology 2006, 30(7), 582-589.
• Howson JMM, Barratt BJ, Todd JA, Cordell HJ. Comparison of population and family-based methods for genetic association analysis in the presence of interacting loci. Genetic Epidemiology 2005,29 1 51-67.
• Cordell HJ. Bias toward the Null Hypothesis in Model-Free Linkage Analysis is Highly Dependent on the Test Statistic Used. American Journal of Human Genetics 2004,74 6 1294-1302.
• Cordell HJ, Barratt BJ, Clayton DG. Case/Pseudocontrol Analysis in Genetic Association Studies: A Unified Framework for Detection of Genotype and Haplotype Associations, Gene-Gene and Gene-Environment Interactions, and Parent-of-Origin Effects. Genetic Epidemiology 2004,26 3 167-185.
• Ueda H, Howson JMM, Esposito L, Heward J, Snook H, Chamberlain G, Rainbow DB, Hunter KMD, Smith A, DiGenova G, Herr MH, Dahlman I, Payne F, Smyth D, Lowe C, Twells RCJ, Howlett S, Healy B, Smink LJ, Lam ACH, Cordell HJ, Walker NM, Bordin C, Hulme H, Motzo C, Cucca F, Hess JF, Metzker ML, Rogers J, Gregory S, Allahabadia A, Nithiyananthan R, Tuomilehto-Wolf E, Tuomilehto J, Bingley P, Gillespie KM, Undlien DE, Rønningen KS, Savage DA, Carson DJ, Maxwell AP, Patterson CC, Franklyn JA, Clayton DG, Peterson LB, Wicker LS, Todd JA, Gough SCL. Association of the T-cell regulatory gene CTLA-4 with susceptibility to autoimmune disease. Nature 2003, 423(6939), 506-511.
• Cordell HJ, Clayton DG. A Unified Stepwise Regression Procedure for Evaluating the Relative Effects of Polymorphisms within a Gene Using Case/Control or Family Data: Application to HLA in Type 1 Diabetes. American Journal of Human Genetics 2002, 70(1), 124-141.
• Johnson GC, Esposito L, Barratt BJ, Smith AN, Heward J, Di Genova G, Ueda H, Cordell HJ, Eaves IA, Dudbridge F, Twells RC, Payne F, Hughes W, Nutland S, Stevens H, Carr P, Tuomilehto-Wolf E, Tuomilehto J, Gough SC, Clayton DG, Todd JA. Haplotype tagging for the identification of common disease genes. Nature Genetics 2001, 29(2), 233-237.
• Cordell HJ, Wedig GC, Jacobs KB, Elston RC. Multilocus linkage tests based on affected relative pairs. American Journal of Human Genetics 2000, 66(4), 1273-1286.