Jonathan Marchini's Home Page

I am a University Lecturer in Statistical Genomics in the Mathematical Genetics group,
Department of Statistics , University of Oxford, UK.

I am also a Senior Research Fellow at Mansfield College and the Senior Member of OUCC.

    Address: Department of Statistics, 1 South Parks Road, Oxford OX1 3TG, UK

    Telephone:   01865 271125

Fax: 01865 281333

    E-mail: marchini <at> stats.ox.ac.uk

News Research Publications Software Teaching VSO Links

News

21 Mar 2013 Our paper describing the genetic variation of short insertions and deletions using sequencing data from the 1000 Genomes Project has been published by Genome Research

S. Montgomery, D. Goode, E. Kvikstad, C. Albers, Z. Zhang, X. Mu, G. Ananda, B. Howie, K. Karczewski, K. Smith, V. Anaya, R. Richardson, J. Davis, D. MacArthur, A. Sidow, L. Duret, M. Gerstein, K. Markova, J. Marchini, G. McVean and G. Lunter (2013) The origin, evolution and functional impact of short insertion-deletion variants identified in 179 human genomes. Genome Research doi: 10.1101/gr.148718.112

29 Dec 2012 Our paper describing the SHAPEIT (v2) method is now available from the Nature Methods website

O. Delaneau, J-F. Zagury and J. Marchini (2012) Improved whole chromosome phasing for disease and population genetic studies. Nature Methods 10, 5-6. + [Supplementary Material]

This paper presents a significantly new algorithm for haplotype estimation that combines together the best ideas from IMPUTE2 and SHAPEIT1. The new method clearly outperforms other existing methods in terms of phasing performance and is very competitive computationally.

6 Dec 2012 We have just released a new version of MULTIMIX (v1.1.0). This new version allows for missing data.

4 Dec 2012 We have just released a new versions of SHAPEIT (v2). The paper on this new version has now been accepted in Nature Methods and will appear soon.

10 Nov 2012 Olivier Delaneau has won a Charles Epstein Post-Doctoral Award (worth $2,000) at the ASHG conference in San Francisco for his work on SHAPEIT2. Well done Olivier! Androniki Menelaou made the final of the Pre-Doctoral competition (worth $1,000) but did not win a prize.

7 Nov 2012 Claire Churchhouse's paper has been published in Genetic Epidemiology

C. Churchhouse and J. Marchini (2012) Multiway Admixture Deconvolution Using Phased or Unphased Ancestral Panels. Genetic Epidemiology.

In this paper we develop a method for carrying out admixture deconvolution with more than two source ancestral populations. The method can handle both phased or unphased data from the source and/or sample populations. The method was used to analyze data from Phase 1 of the 1000 Genomes Project which was recently published in Nature. The MULTIMIX software implementing this approach will appear here soon.

1 November 2012 Jonathan Marchini has been awarded a Philip Leverhulme Prize

1 November 2012 The latest 1000 Genomes Project paper has been published in Nature today.

The 1000 Genomes Project Consortium (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56-65.

This is a big international collaboration that has sort to sequence a large number of individuals from around the world with the aim of mapping the majority of the genetic variation with frequency above 1%. Members of our group that contributed to the analysis were Olivier Delaneau, Claire Churchhouse, Jason Liu and myself. The project has been reported in the mainstream press.

1 November 2012 The company Affymetrix has launched a new genotyping chip that was designed using our software IMPUTE2. They have issued a press release here giving the details. http://phx.corporate-ir.net/phoenix.zhtml?c=116408&p=irol-newsArticle&ID=1752709

23 October 2012 Androniki Menelaou's paper has been published in Bioinformatics.

A. Menelaou and J. Marchini (2012) Genotype calling and phasing using next-generation sequencing reads and a haplotype scaffold. Bioinformatics.

In this paper we show that combining low-coverage sequence data with microarray genotyping on the same subjects can lead to high quality haplotype reference sets that produce a notable boost in downstream imputation accuracy. The MVNcall software implementing this approach will appear here soon.

2 October 2012 Jared O'Connell won the poster prize at the recent Genomics of Common Diseases conference in Potomac, MD, USA.

27 August 2012 We have done very well this year with accepted talks at the American Society of Human Genetics meeting. Olivier Delaneau and Androniki Menelaou have made the final of the post-doctoral and pre-doctoral Charles J. Epstein Trainee Awards

24 August 2012 Claire Churchouse has succesfully passed her viva. Her thesis entitled 'Bayesian Methods for Estimating Human Ancestry Using Whole Genome SNP Data' was examined be Dr Lachlan Coin and Dr Simon Myers. Claire is now off to start a postdoc with David Althuler at the Broad Institute of Harvard and MIT. Good luck Claire!

22 July 2012 Our new paper (with Bryan Howie as co-lead author) on pre-phasing based imputation has now appeared in Nature Genetics.

B. Howie, C. Fuchsberger, M. Stephens, J. Marchini, G. Abecasis (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nature Genetics. DOI: 10.1038/ng.2354

20 July 2012 Jared O'Connell's paper on a new method for calling genotypes from array and sequence data has now appeared in Genetic Epidemiology

J. O'Connell, J. Marchini (2012) Joint Genotype Calling With Array and Sequence Data. Genetic Epidemiology. DOI: 10.1002/gepi.21657

29 June 2012 Androniki Menelaou has succesfully passed her viva. Her thesis entitled 'LD-based SNP and genotype calling from next-generation sequencing reads" was examined be Dr Vincent Plagnol and Prof Gil McVean. Androniki is now off to start a postdoc with Paul de Bakker at UMC Utrecht. Good luck Androniki!

30 April 2012 Victoria Hore has joined the group for her DTC project. Welcome Vicky!

12 April 2012 Warren Kretzschmar has joined the group for his rotation project. Welcome Winni!

15 March 2012 Olivier Delaneau's paper on the SHAPEIT method has now appeared in Nature Methods

O. Delaneau, J. Marchini, JF. Zagury (2012) A linear complexity phasing method for thousands of genomes. Nature Methods doi:10.1038/nmeth.1785

Research

The main focus of my research is the development of statistical methods for the localization, detection and characterization of the genes that underly human disease. Some of the areas we are currently working on include

Analysis of next-generation sequencing data, specifically analysis of the 1000 Genomes project data.
SNP genotype calling
CNV detection and genotyping
Methods for detecting gene-gene interactions
Haplotype inference
Genotype imputation
Coalescent based approaches for detection and fine-mapping of disease genes in association studies
Bayesian modelling of genotype-phenotype association
Methods for detection of population structure from genetic datasets

I am also interested in statistical image analysis and pattern recognition and have collaborated with the The Oxford Centre for Functional Magnetic Resonance Imaging of the Brain (FMRIB).

I currently hold an MRC New Investigator award.

Group Members and Collaborators

Post-Docs (current)

Olivier Delaneau

Post-Docs (past)

Niall Cardin (now at UCSF)
Jason Liu

DPhil Students (current)

Valentina Iotchkova
Eleni Frangou
Peter Kecskemethy (jointly supervised with Chris Holmes) [DTC student]
Jared O'Connell
Marie Forest (jointly supervised with Simon Myers)
Melissa Maczka (jointly supervised with Chris Martin and Mark Woolrich) [DTC student]
Victoria Hore [DTC student]
Warren Kretzschmar

DPhil Students (past)

Claire Churchhouse (now a postdoc at the Broad Institute of Harvard and MIT)
Androniki Menelaou (now a postdoc at UMC Utrecht)
Teresa Ferreira (now a postdoc at WTCHG, Oxford)
Joanne Gale
Bryan Howie (now a postdoc at Chicago)
Robert Johnson (based at the FMRIB Center)
Zhan Su (now a postdoc at WTCHG, Oxford) [DTC student]

Projects

Collaborators

Nicole Soranzo (Wellcome Trust Sanger Institute)
Paolo Gasparini and Nicola Piratsu (University of Trieste)
Jonathan Flint (Wellcome Trust Center for Human Genetics, Oxford)
Bryan Howie (University of Chicago)
Caroline Relton and George Davey-Smith (University of Bristol)

Publications

2013

O. Delaneau, J-F. Zagury and J. Marchini (2013) Improved whole chromosome phasing for disease and population genetic studies. Nature Methods 10, 5-6. [Link] [Supplementary Material] [Software]
A. Menelaou and J. Marchini (2013) Genotype calling and phasing using next-generation sequencing reads and a haplotype scaffold. Bioinformatics 29(1):84-91 [Link]
C. Churchhouse and J. Marchini (2013) Multi-way admixture deconvolution using phased or unphased ancestral panels. Genetic Epidemiology 37(1):1-12 [Link] [Software]
S. Montgomery, D. Goode, E. Kvikstad, C. Albers, Z. Zhang, X. Mu, G. Ananda, B. Howie, K. Karczewski, K. Smith, V. Anaya, R. Richardson, J. Davis, D. MacArthur, A. Sidow, L. Duret, M. Gerstein, K. Markova, J. Marchini, G. McVean and G. Lunter (2013) The origin, evolution and functional impact of short insertion-deletion variants identified in 179 human genomes. Genome Research doi: 10.1101/gr.148718.112 [Link]

2012

The 1000 Genomes Project Consortium (2012) An integrated map of genetic variation from 1,092 human genomes. Nature 491, 56-65. [Link]
B. Howie, C. Fuchsberger, M. Stephens, J. Marchini, G. Abecasis (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nature Genetics. DOI: 10.1038/ng.2354 [Link] [Software]
O. Delaneau, J. Marchini, JF. Zagury (2012) A linear complexity phasing method for thousands of genomes. Nature Methods doi:10.1038/nmeth.1785 [Link]
[Software]
J. O'Connell, J. Marchini (2012) Joint Genotype Calling With Array and Sequence Data. Genetic Epidemiology. DOI: 10.1002/gepi.21657 [Link] [Software]
J. Wang et al. (2012) Genome-wide association analysis implicates the involvement of eight loci with response to tocilizumab for the treatment of rheumatoid arthritis. The Pharmacogenomics Journal doi: 10.1038/tpj.2012.8

2011

B. Howie, J. Marchini, M. Stephens (2011) Genotype Imputation with Thousands of Genomes. G3 : Genes, Genomes, Genetics. doi: 10.1534/g3.111.001198 [Link] [Software]
N. Cardin, C. Holmes, WTCCC, P. Donnelly, J. Marchini (2011) Bayesian hierarchical mixture modeling to assign copy number from a targeted CNV array. Genetic Epidemiology DOI: 10.1002/gepi.20604 [Link]
Z. Su, J. Marchini, P. Donnelly (2011) HAPGEN2: simulation of multiple disease SNPs. Bioinformatics. doi: 10.1093/bioinformatics/btr341 [Link] [Software]
T. Ferreira and J. Marchini (2011) Modeling interactions with known risk loci—a Bayesian model averaging approach. Annals of Human Genetics 75 (1) 1-9 [Link]
M.Soler Artigas et al. (2011) Genome-wide association and large-scale follow up identifies 16 new loci influencing lung function. Nature Genetics 43 1082-90 [Link]
I. Tomlinson et al. (2011) Multiple common susceptibility variants near BMP pathway loci GREM1, BMP4, and BMP2 explain part of the missing heritability of colorectal cancer. PLoS Genet 7(6):e1002105
L. Southam et al. (2011) The effect of genome-wide association scan quality control on imputation outcome for common variants. Eur J Hum Genet 19(5):610-614

2010

J. Marchini and B. Howie (2010) Genotype imputation for genome-wide association studies. Nature Reviews Genetics [Link]
J. Liu et al. (2010) Meta-analysis and imputation refines the association of 15q25 with smoking quantity. Nature Genetics 42, 436–440 [Link].
Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls. Wellcome Trust Case-Control Consortium. Nature. 2010;464;713-20. [Link]
The 1000 Genomes Consortium (2010) A map of human genome variation from population-scale sequencing. Nature 467, 1061–1073 [Link]

2009

Z. Su, N. Cardin, WTCCC, P. Donnelly, J. Marchini (2009) A Bayesian method for detecting and characterizing allelic heterogeneity and boosting signals in genome-wide association studies. Statistical Science 24(4) 430-450. [Article pdf] [Supplementary Material] [Software]
B. Howie, P. Donnelly, J. Marchini (2009) A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies. PLoS Genetics 5(6): e1000529 [Open Access Article]
C. Spencer, Z. Su, P. Donnelly, J. Marchini (2009) Designing Genome-Wide Association Studies: Sample Size, Power, Imputation, and the Choice of Genotyping Chip. PLoS Genetics 5(5). [Link] [Software]
M. Jallow et al. (2009) Genome-wide and fine-resolution association analysis of malaria in West Africa. Nature Genetics 41, 657 - 665 (2009)
M. O'Donovan et al. (2009) Analysis of 10 independent samples provides evidence for association between schizophrenia and a SNP flanking fibroblast growth factor receptor 2. Mol Psychiatry. 2009 Jan;14(1):30-6

2008

C. Barnes, V. Plagnol, T. Fitzgerald, R. Redon, J. Marchini, D. Clayton, M. Hurles (2009) A robust statistical method for case-control association testing with copy number variation. Nature Genetics Oct;40(10):1245-52.
J. Barrett et al. (2008) Genome-wide association defines more than 30 distinct susceptibility loci for Crohn's disease. Nat Genet 40(8):955-962 Aug 2008 23.
R. Loos et al. (2008) Common variants near MC4R are associated with fat mass, weight and risk of obesity. Nat Genet 40(6):768-775. 24.

2007

J. Marchini, B. Howie, S. Myers, G. McVean and P. Donnelly (2007) A new multipoint method for genome-wide association studies via imputation of genotypes. Nature Genetics 39 : 906-913 [Free Access PDF][Supplementary Material][News and Views Article]
The Wellcome Trust Case Control Consortium (2007) Genomewide association study of 14,000 cases of seven common diseases and 3,000 shared controls. Nature 447;661-78. PMID: 17554300 DOI: 10.1038/nature05911.
The International HapMap Consortium (2007) A second generation human haplotype map of over 3.1 million SNPs. NATURE 449(7164):851-U3 18
Zeggini et al. (2007) Replication of genome-wide association signals in UK samples reveals risk loci for type 2 diabetes. Science. Jun 1;316(5829):1336-41. Epub 2007 Apr 26. (link)
M. Newport et al. (2007) Association scan of 14,500 nonsynonymous SNPs in four diseases identifies autoimmunity variants. NAT GENET 39(11):1329-1337.

2006

J. Marchini, D. Cutler, N. Patterson, M. Stephens, E. Eskin, E. Halperin, S. Lin, Z.S. Qin, H.M. Munro, G.R. Abecasis, P. Donnelly, and International HapMap Consortium (2006) A Comparison of Phasing Algorithms for Trios and Unrelated Individuals. Amercan Journal of Human Genetics, 78 437-450 [PDF] [Datasets].
P. De Bakker et al. (2006) A high-resolution HLA and SNP haplotype map for disease association studies in the extended human MHC. Nat Genet 38(10):1166-1172.
D. Evans, J. Marchini, A. Morris, J. Cardon (2006) Two-stage two-locus models in genome-wide association. PLoS Genet 2(9):e157

2005

J. Marchini, P. Donnelly and L. R Cardon (2005) Genome-wide strategies for detecting multiple loci influencing complex diseases. Nature Genetics, 37 413-417 [PDF] [Supplementary Material] [News and Views article]
The International HapMap Consortium. A haplotype map of the human genome. Nature 437, 1299-1320. 2005. [Abstract] [PDF]

2004

J. Marchini, L. Cardon, M. Phillips, and P. Donnelly (2004) The effects of human population structure on large genetic association studies. Nature Genetics 36 512 - 517. [PDF]
The International HapMap Consortium (2004). Integrating ethics and science in the International HapMap Project. Nature Reviews Genetics, 5 467-475. [PDF]
J. Marchini and A. Presanis (2004) Comparing methods of analysing fMRI statistical parametric maps. NeuroImage, 22 (3) 1203-1213

2003

Marchini, J. L. and Cardon, L. R., (2003) Discussion of Nicholson et al. (2003) Assessing population differentiation and isolation from single-nucleotide polymorphism data. JRSS(B) 740-1.
The International HapMap Consortium (2003). The international HapMap project. Nature 426 789-796. [PDF]
Marchini, J. L. and Smith, S. M., (2003) On bias in the estimation of autocorrelations for fMRI voxel time series analysis. NeuroImage 18: 83-90
Henry, C. J. K., Lightowler, H. J. and Marchini, J. (2003) Intra-individual variation inresting metabolic rate during the menstrual cycle. British Journal of Nutrition 89, 811-817

2002

Marchini, J. L. (2002) AnalyzeFMRI: An R package for the exploration and analysis of MRI and fMRI datasets. R News 2 (1): 17-23

2001

Banks, A. N., Marchini, J. L. and Guilford, T.C. (2001) Resolving navigational conflict: clock-shift experiments with homing pigeons. Proc. Royal Institute Navigation Conference, Oxford.

2000

Marchini, J. L., and Ripley, B. D., (2000) A New Statistical Approach to Detecting Significant Activation in Functional MRI. NeuroImage 12: 366-380

1997

Crichton, N. J., Hinde, J. P., and Marchini, J. L., (1997) Models for Diagnosing Chest Pain: Is CART helpful? Statistics in Medicine 16: 717-727

Software

Genome-wide Association Study Software

R Packages

popgen - R package for statistical and population genetics
fastICA - R package that implement the FastICA alsgorithm
AnalyzeFMRI - R package for visualisation and analysis of FMRI data
GWApower - R package for estimating the power of genome-wide association studies
JMisc - R package for miscellaneous code

Teaching

At Mansfield College

I give tutorials in Probability and Statistics to 1st and 2nd year students studying Maths or Maths and Statistics.

In the Statistics Department, University of Oxford

Outside Oxford

Wellcome Trust Advanced Course : Design and Analysis of Genetic-Based Association Studies

VSO

Between September 1995 and September 1998 I worked as a VSO volunteer in Tanzania, teaching A-level Mathematics in a rural government run school near Iringa (map).

VSO enables men and women to work alongside people in poorer countries in order to share skills, build capabilities and promote international understanding and action, in the pursuit of a more equitable world.

If you are at all interested in applying to VSO and want to know more check out the webpage Volunteer with VSO

Here are some pictures which I hope give you an idea of the time I spent in Tanzania.