Paul O'Reilly

I am a Senior Lecturer in Statistical Genetics at the MRC SGDP Centre, Institute of Psychiatry, King's College London. I did my PhD at Imperial College London on detecting recent positive selection in the human genome, supervised by David Balding and co-supervised by Ewan Birney. After a post-doc with Marjo-Riitta Jarvelin and Lachlan Coin, working on numerous GWAS projects and methodology development focused on multivariate GWAS (MultiPhen) and inversion polymorphisms, I began a lectureship in the same dept. in 2011, before moving to King's in October 2013. I'm interested in working on quantitative problems in population genetics and genetic epidemiology.

Contact: paul.oreilly@kcl.ac.uk
twitter.com/paul_f_oreilly

Methods & Software

• PRSice ('precise') software - for performing Polygenic Risk Score (PRS) analysis. Command-line program that performs the multi-stage PRS process: calculation, application, evaluation and plotting of results (exploiting R, bash and PLINK2). A feature of PRSice is that it can calculate PRS at 'high-resolution' to find the best-fit PRS - for more details, and to download, see the PRSice webpage or our Bioinformatics paper on PRSice. All the coding for PRSice was done by Jack Euesden (PLINK2 by Shaun Purcell & Chris Chang).
• MultiPhen method - for modelling and testing multiple phenotypes jointly in GWAS. This method is fast and can be applied to imputed data, and is available as a CRAN package (see here) that can also perform standard univariate GWAS. Paper describing the method, with results on the NFBC data, here.

• Ped/Pop method - for detecting recent positive selection. Compares population-based recombination rate estimates (underestimated due to recent common ancestor at selected locus) with pedigree-based recombination rate estimates (unaffected by selection). Paper describing the method here.

• invertFREGENE - software for simulating inversion polymorphisms in population genetic data. Paper describing the software and showing the patterns of variation at simulated and real inversions is here. Documentation and code:
  • invertFREGENE.pdf
  • invertFREGENE.tar.gz

• BAYESFST - software/method for detecting selection. Method described in Beaumont and Balding (2004) takes a Bayesian approach to identifying loci with divergent allele frequencies between sub-populations (based on Fst). Contributed to the software code by extending to deal with genome-wide linked markers, primarily by incorporation of a prior term between hyper-parameters to model the correlation between adjacent markers. The program, implemented via MCMC, and coded in C, can be downloaded here.

• BranchSort - algorithm that produces the gene tree at a locus without recombination from a sample of genotype data (thus phasing the data into haplotypes). Planning to publish at some point - but contact me if this would be useful. The future plan is to build a gene tree incorporating recombination - currently works for a small number of recombination events.

Publications

Chadeau-Hyam, M., Hoggart, CJ., O'Reilly, PF., Whittaker, JC., De Iorio, M., and Balding, DJ. 2008. Fregene: Simulation of realistic sequence-level data in populations and ascertained samples. BMC Bioinformatics. 9: 364.

Analysis:

Krapohl, E. et al. 2015. Phenome-wide analysis of genome-wide polygenic scores. Mol.Psychiatry. doi: 10.1038/mp.2015.126

Ojelade, SA. et al. 2015. Rsu1 regulates ethanol consumption in Drosophila and Humans. PNAS. 112: E4085-93.

Pourcain, BS. et al. 2014. Common variation near ROBO2 is associated with expressive vocabulary in infancy. Nature Comm. 5: 4831

Walsh, KM. et al. 2014. Variants near TERT and TERC influencing telomere length are associated with high-grade glioma risk. Nature Genet. 46: 731-5

Buxton, JL. et al. 2014. Multiple Measures of Adiposity Are Associated with Mean Leukocyte Telomere Length in Northern Finland Birth Cohort 1966 PLoS ONE 9: 99133

Chambers, JC. et al. 2014. The South Asian Genome. PLoS ONE 9: e102645

Song, YQ. et al. 2013. Lumbar disc degeneration is linked to carbohydrate sulfotransferase 3 variant. J Clin Invest 123: 4909-17

Codd, V. et al. 2013. Identification of seven loci affecting mean telomere length and their association with disease. Nature Genetics 45: 422-427

den Hoed, M. et al. 2013. Identification of heart rate-associated loci and their effects on cardiac conduction and rhythm disorders. Nature Genetics doi:10.1038/ng.2610

Kujala, U.M. et al. 2013. Long-term leisure-time physical activity and serum metabolome. Circulation 127: 340-348

van de Harst, P. et al. 2012. Seventy-five genetic loci influencing the human red blood cell. Nature doi:10.1038/nature11677

Taal, HR. et al. 2012. Common variants at 12q15 and 12q24 are associated with infant head circumference. Nature Genetics 44: 532-538

Tukiainen, T. et al. 2012. Detailed metabolic and genetic characterization reveals new associations for 30 known lipid loci. Hum Mol Genet. doi: 10.1093/hmg/ddr581

Wain, LV.*, Verwoert, GC.*, O'Reilly, PF.*, et al. 2011. Genome-wide association study identifies six new loci influencing pulse pressure and mean arterial pressure. Nature Genetics 43: 1005–1011

Ehret et al. 2011. Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478: 103–109

Gieger, C. et al. 2011. New gene functions in megakaryopoiesis and platelet formation. Nature 480:201-208

Schumann et al. 2011. Genome-wide association and genetic functional studies identify AUTS2 in the regulation of alcohol consumption. PNAS 10.1073/pnas.1017288108

Kraja et al. 2011. A bivariate genome-wide approach to metabolic syndrome: STAMPEED Consortium. Diabetes 60: 1329-39.

Fox, ER. et al. 2011. Association of genetic variation with systolic and diastolic blood pressure among African Americans: the Candidate Gene Association Resource study. Hum. Mol. Gen. 20: 2273-84.

Kilpeläinen, TO. et al. 2011. Obesity-susceptibility loci have a limited influence on birth weight: a meta-analysis of up to 28,219 individuals. Am.J.Clin.Nutr. 93: 851-60.

Wang et al. 2010. Common genetic determinants of Vitamin D insufficiency: the SUNLIGHT consortium. The Lancet.

Pillas, D.*, Hoggart, CJ.*, Evans, D.*, O'Reilly, PF.*, et al. 2010. Genome-wide association study reveals multiple loci associated with primary tooth development. PLoS Genetics. 6(2): e1000856.

Freathy et al. 2010. Variants at two loci (in ADCY5 and near CCNL1) influence fetal growth and birth weight. Nature Genetics. 42, 430-435

Ikram, MK. et al. 2010. Four novel Loci influence the microcirculation in vivo. PLoS Genetics. 6(10): e1001184

Tabara, Y. et al. 2010. Common variants in the ATP2B1 gene are associated with susceptibility to hypertension: the Japenese Millennium Genome Project. Hypertension 56(5): 973-80.

Newton-Cheh et al. 2009. Five blood pressure loci identified by genome-wide association study of 26,644 people. Nature Genetics. 41, 666-676.

Sovio, U. et al. 2009. Genetic determinants of height growth assessed longitudinally from infancy to adulthood in the Northern Finland Birth Cohort 1966. PLoS Genetics. 5(3): e1000409.

Talks

EMGM, Heidelberg, Apr 2007. “Confounding between recombination and selection, & the Ped/Pop method...” (abstract in Annals of Human Genetics, Jul 2007)

Teaching

Other roles