The Wellcome Trust Centre for Human Genetics - DOC by liwenting



Job Description
Job Title:              Post Doctoral Research Scientist in Statistical Genetics

Tenure:                 24 months in the first instance.

Grade:                  Grade 7, £28,983 to £35,646 with a discretionary range to £38,951

Funded By:              The Wellcome Trust


The groups led by Dr Andrew Morris, Dr Cecilia Lindgren and Prof Mark McCarthy at the Wellcome Trust
Centre for Human Genetics, and by Dr Eleftheria Zeggini at the Wellcome Trust Sanger Institute plan to
make a joint appointment for an experienced statistical geneticist. The main focus of the work will relate
to transethnic fine-mapping efforts in type 2 diabetes, making use of data and resources arising from the
NIH-funded T2D-GENES study. This international collaborative effort has access to extensive genome-
wide association data from multiple ethnic groups, and is generating substantial genome-scale next-
generation sequence data. The person appointed will take a leading role in the analysis of these data.
The successful candidate will have a PhD in a relevant subject, experience of analysing genome-scale
association data from diverse ethnic groups, a thorough understanding of imputation procedures,
familiarity with diabetes genetics, and previous involvement in international research efforts. The post
will be based at the Wellcome Trust Centre for Human Genetics, but the candidate will be expected to
spend part of the project at the Wellcome Trust Sanger Institute. We anticipate substantial interactions
with colleagues in the US and elsewhere.


The environment: The Wellcome Trust Centre for Human Genetics
The WTCHG (Director: Professor Peter Donnelly, FRS) is one of the leading international centres for the
study of the genetic basis of common human diseases. As well as hosting a number of high-profile
groups pursuing the genetic basis of diabetes, cardiovascular disease and neuropsychiatric phenotypes
(amongst others), the WTCHG has led the efforts of the Wellcome Trust Case Control Consortium and
been responsible for advancing the application of large-scale genetic analysis to the dissection of
common human phenotypes. The centre provides a unique integrated environment – including core
genomics facilities, bioinformatics and statistical genetics. Since 2005, there have been 40 publications
in Nature, Science, Nature Genetics, Nature Medicine, Nature Immunology, Nature Structural and
Molecular Biology, Cell, or Molecular Cell on which Centre scientists have earned either first or last
author positions, and a further 34 papers in these journals on which Centre scientists have collaborated.

The WTCHG provides an extremely strong computing infrastructure for genetic analysis and has recently
invested heavily in high-throughput next-generation resequencing. The WTCHG currently has installed 7
Illumina and 2 Roche/454 high-throughput (HT) sequencers.

The WTCHG forms part of the Nuffield Department of Medicine at the University of Oxford, one of the
strongest departments of clinical academic medicine in the country (see for further
The project: Trans-ethnic fine mapping in type 2 diabetes
This post is funded through grants from the US National Institutes of Health and the Wellcome Trust,
and will be focused around the trans-ethnic fine mapping of type 2 diabetes loci. Though genome wide
association scans have identified ~40 loci influencing T2D-risk, in very few cases have the variants causal
for the association been characterised. Extensive linkage disequilibrium typically means that, even after
exhaustive sequencing has been performed, within any given population, a number of highly-correlated
SNPs show indistinguishable evidence for association. It has long been suspected that one might be able
to refine the associations further if one had access to data from diverse ethnic groups (particularly, but
not exclusively, those of African origin) since differences in the patterns of LD and haplotypes might
allow the effects of variants that are closely-correlated in one population to be distinguished.

The availability of large-scale GWAs data for many different major ethnic groups, together with
increasingly comprehensive surveys of common and low frequency variation (arising from the 1000
Genomes Project for example) means that it is now possible to conduct transethnic fine mapping studies
of this kind, and the position being advertised will be involved in efforts to do precisely this for T2D.

The work will take place in the context of the T2D-GENES consortium, funded by NIDDK to a total of
$25M through the U01 mechanism in 2009. The consortium includes many of the major groups
worldwide working on T2D genetics, and provides access to many T2D case-control samples of diverse
ethnic origin (many of which have already been GWAS’d). The consortium is using its funding to
undertake a number of targeted and exome-sequencing projects designed to identify low frequency and
rare variants influencing T2D risk, but it is also devoting efforts to perform fine-mapping of the original
common variant signals using a range of in silico approaches. These efforts are broadly based around
taking existing GWAs data, performing imputation from 1000 Genomes, and then using a range of
different analytical approaches to identify putatively causal variants (under a range of different possible

Whilst the person in post will likely be involved in several different aspects of the evolving T2D-GENES
consortium effort, the primary responsibility in the first year at least will be to support the common-
variant fine-mapping analyses described above. This particular subproject is currently being run by a
group of investigators based in Oxford, Sanger and Singapore, each of which has developed or is
championing an alternative analytical approach. As well as comparing these different approaches
through simulations, we are also gathering data from GWAS’d cohorts of diverse transethnic
backgrounds so we pipe these through the various analytical approaches and determine how well they
correspond in terms of their findings. WE are initiating this project through analysis of five T2D-
susceptibility loci of particular interest, but expect to expand the project more widely over the course of
the next year (ultimately to genome-wide analyses).

The group leaders

Mark McCarthy is Robert Turner Professor of Diabetes at the Oxford Centre for Diabetes, Endocrinology
and Metabolism and Group Head at the Wellcome Trust Centre for Human Genetics. He heads one of
the leading international groups working on the genetics of type 2 diabetes and related conditions.

Andrew Morris is a Wellcome Trust Senior Fellow at the Wellcome Trust Centre for Human Genetics. He
has interests in the development of novel statistical approaches to genetic analysis, and in their
application to genome-scale data.

Cecilia Lindgren is a Wellcome Trust Career Development Fellow at the Wellcome Trust Centre for
Human Genetics. She is vastly experienced in the analysis of genetic and genomic data, and has a
particular interest in the genetics of obesity and fat distribution.
Eleftheria Zeggini is an Investigator at the Wellcome Trust Sanger Institute, with extensive experience in
the development and application of novel statistical methods for the analysis of genome-scale data. She
has particular interest in the evaluation of the contribution of low frequency variants to common
disease etiology.

All four groups work extremely closely on a variety of common projects including the T2D-GENES
consortium projects on T2D fine-mapping.

The Post

We are looking to appoint a postdoctoral scientist with the skills already in place that will allow them to
contribute substantively to the work outlined above. The research will involve the manipulation and
analysis of very large (genome-scale) data sets (eg GWA data sets, 1000Genomes imputation), so
existing experience in this area will be absolutely essential. As well as generating data from existing T2D
case-control GWA analyses, the person in post will be involved in the collation of such data from
multiple ethnic groups, and then for the analysis of those data using some of the analytical approaches
that the group collectively plans to apply (these include TRANSMAP, AMELIA and CAUSAL-SEEK). As
results emerge, the person in post will have responsibility for comparing the outputs of the different
programs, to identify putatively causal alleles that can be put forward for further validation and/or
functional evaluation.

In addition to this work on the common variant transethnic mapping project, we expect the person in
post to become involved with other efforts of the T2D-GENES consortium, as well as other major
projects underway in the Oxford and Sanger groups. These include the GOT2D project which is currently
obtaining genome-wide sequence data on ~1500 t2D cases and 1500 controls as a means to evaluate
the role of low frequency variants on T2D risk.

Given the nature of the project (and the short time-lines for implementation), we will be looking to
appoint only those individuals who can demonstrate considerable relevant experience. We expect this
to include a PhD or equivalent in a relevant subject (natural sciences, mathematics, statistics, computer
science, genetics, biology), though, exceptionally, we would consider applications from those without a
PhD if they can demonstrate a significant body of work of post-doctoral quality, or extensive industrial
experience in the management of large, complex data sets.

The post will be based at the Wellcome Trust Centre for Human Genetics in Oxford, though we
anticipate that at least part of the project will be undertaken at the Wellcome Trust Sanger Institute
(where the person in post would be granted a Visiting Fellowship). There will also be extensive
interactions with other groups in the T2D-GENES consortium and other major projects ongoing in the


Main responsibilities

   To report to Prof McCarthy and Drs Morris, Zeggini, Lindgren, meeting regularly to ensure that
    appropriate work is performed;
   To develop, implement and maintain software pipelines required to pursue the objectives of the
   To manage data generated by the project;
   To participate in group meetings, generate high-quality manuscript, and contribute to discussions of
    the aims and objectives of the group;
   To contribute ideas and communicate effectively with all project participants including international
    travel where required;
   To keep abreast of the relevant literature and methodology developments as they pertain to the
   To hold frequent discussions with other members of the T2D-GENES consortium and other groups
    that may be relevant to pursuit of the objectives of the research;
   To perform any other comparable duties as may reasonably be required to ensure the efficient
    running of the project.

General responsibilities
 To be accountable for your professional conduct within the Group and the Centre
 To undertake such other duties as may be required from time to time that are commensurate with
    the grade and responsibilities of this post.
 To ensure such that all conduct is with due regard to the University Equal Opportunities and Data
    Protection policies


The primary responsibilities for line management will rest with Prof McCarthy and Dr Morris, though the
person in post will also interact closely with Dr Lindgren and Dr Zeggini and other members of their

Other relationships will include:

       Prof Peter Donnelly (as Director of the WTCHG)
       Dr Mike Boehnke (as leader of the T2D-GENES consortium)

Selection criteria

     PhD in a relevant subject
     Proven experience in the genetic analysis of multifactorial traits
     Experience in analysing genome-scale association data
     Practical understanding of imputation procedures

     Experience in analysing genome-scale association data from diverse ethnic groups
     Experience of working on the genetics of type 2 diabetes
     Practical experience of working as part of an international collaborative team
     A good understanding of other aspects of the project including epidemiology, genomics and/or
        molecular biology, and project management

Working for the University of Oxford

At the University of Oxford, we’re naturally very proud of our outstanding reputation for scholarship and
research. But we’re also proud to say that we’re one of the region’s biggest and best-established
employers, with a diversity of staff helping to sustain our success – from laboratory assistants, cleaners,
technicians and secretaries, to IT, finance and administrative professionals. Join us, and you can expect
to find yourself working in a friendly, open-minded atmosphere where your ideas will be welcomed, with
an interesting and satisfying job to do, and with plenty of opportunities to learn new skills, or maybe
even get some extra qualifications.
As well as pay and other benefits such as generous holidays and excellent pension scheme, we may be
able to help you with:

       Training – We train our staff, both in the skills needed for starting the job, and to help them
        develop afterwards. If you don’t have all the skills we are looking for (e.g. computer packages),
        but you know you are a quick learner, its worth asking if training might be available.
       Working Hours – We may be able to be flexible about working patterns to help you combine
        work with responsibilities at home. Even for full-time jobs, we can often adjust starting and
        finishing times, or even sometimes consider term-time-only working: if this is important to you,
        let us know.
       Disability – If you have a disability, we have specialist staff who can help you to start and stay in
       Childcare – We have several subsidised nurseries for under-fives, a holiday play scheme, tax and
        national insurance savings schemes, and are looking to expand our facilities. For further
        information see
       Parenting – As well as providing childcare facilities, we have generous maternity; paternity and
        adoption leave schemes to help new parents on our staff.
       Cultural and Religious needs – We respect the cultural and religious lives of our staff. If you
        need time away from work, or special facilities, and can give plenty of notice for arrangements
        to be made, this will always be considered.
       Travel Arrangements – We offer an interest free-season ticket loan scheme for bus or train
        season tickets. Annual passes for Oxford Bus Company routes are available at discounted rates.
       Use of University Facilities – All University staff can use the study facilities provided by the
        University libraries and museums; join the University Club, a sports and social club which has its
        own bar, café, and reading room; and make use of the University Sports Complex and the Pulse
        fitness centre.
       Discounts – A number of discounts are available to University staff e.g. for insurance, holiday
        travel, and computer equipment.

The range of benefits is continuously reviewed and extended. For further information see

If you come from outside the area, you may be interested to know that as well as the famous tourist
attractions such as the ‘dreaming spires’ of all the lovely old buildings, the river and a number of
attractive parks and gardens, Oxford also has a busy shopping centre and a lively nightlife, particularly
during term time. Housing is relatively expensive within the city, but nearby areas are more reasonable
priced. Although car parking is difficult during the day, there are good train and bus services, including
several ‘Park and Ride’ routes; and of course, lots of cycle paths.

The University has a generous maternity leave scheme and also offers paternity leave to expectant
fathers and partners, and adoption leave. It offers subsided nursery places, a holiday playscheme, and
tax and National Insurance savings schemes. For further information see

Pay and Benefits

The salary offered for full-time appointment to this job will be grade 7 (£28,983 to £35,646, with a
discretionary range to £38,951). There is an annual ‘cost of living’ salary review, which normally takes
place in summer each year. Pay and benefits for part-time appointments are worked out on a ‘pro rata’
For a full-time appointment, the annual holiday entitlement will be 38 days (including 8 public holidays).
Your hours of work are such as are reasonably required to carry out your duties to the satisfaction of
your head of department.

The appointment is subject to satisfactory completion of a 6 month probationary period, during which
the notice period will be one month on either side. Once the appointment has been confirmed, the
notice period will be three months either side.

The position is available for 24 months in the first instance and will be funded by the Wellcome Trust.


The age of retirement for university appointments is 65. Staff are eligible to join the Universities
Superannuation Scheme (USS) which is a contributory scheme. Subject to the Statement of Pensions
Policy, which will be issued to the successful candidate, the appointee will be deemed to be in
membership of the USS until such time as he or she gives notice in writing to exercise the right not to be
a member of the scheme. The Wellcome Trust Centre for Human Genetics has a NO SMOKING policy.

How to apply

To apply, please write a letter of application and send a detailed CV and return it to:

Personnel Administrator
Wellcome Trust Centre for Human Genetics
Roosevelt Drive
or by fax to 01865 287516 or email to by no later than Friday 30th July 2010.
Applicants received after this date will not be considered. Please make sure you quote reference number
H5-10-042-CL at the beginning of your application.
The list of duties and the ‘selection criteria’ for this job describe the sort of skills, experience, knowledge
or abilities which we are looking for. We will interview those whose applications best meet these criteria,
so it is very important that you should use your application to explain how you can match them.
Remember that you will have gained abilities, experience and skills from many aspects of your life; some
may come from education or work, and others from home or community life. Tell us about which schools
or colleges you went to and any qualifications you have. List employment, voluntary work, hobbies, or
family responsibilities which help to show you meet the selection criteria.

Please give the names, addresses and telephone numbers of two people you are prepared to give you a
reference for this job. If you have previously been employed, your referees should be people who have
direct experience of your work through closely working with you for a considerable period, and at least
one of them should be your formal line manager in your most recent job. Otherwise they can be people
who know you from recent college, school, or voluntary experience. It is helpful if you can tell us briefly
how each referee knows you (e.g. ‘line manager’. ‘Work colleague’, ‘college tutor’).

Your referees will be asked to look at the job details and tell us if, in their opinion, you could do the job.
We will assume that we can approach them at any stage unless you tell us otherwise when you apply.
So, if you wish us to ask for your permission before approaching a particular referee, or to contact them
only under your circumstances (for example if we are calling you for a interview, or if we have made you
a conditional offer), you must state this explicitly alongside the details of the relevant referee(s).
Your appointment will be subject to (i) the return of a completed medical questionnaire which is
acceptable to the University, (ii) the provision of original documentation which indicates your right to
work in the UK, and (iii) the completion of an initial probationary period of 6 months.

Please note that due to the volume of applications we receive it will only be possible for us to contact
those who have successfully been shortlisted to attend interview.

Equal opportunities at the University of Oxford

As an Equal Opportunity employer, we positively encourage applications from people of different
backgrounds. All our jobs are filled in line with our equal opportunities code of practice, which helps us
make sure that men and women, people of different races, and those with disabilities are all treated

If you have any questions about equal opportunities at the University of Oxford, please visit our website

General Responsibilities

To participate and support public engagement activities on behalf of the Centre, working with the
Centre’s Public Engagement and Communications Officer. This is anticipated to be around 2 days per

Data Protection

All data supplied by applicants will be used only for the purpose of determining their suitability for the
post, and will be held in accordance with the principles of the Data Protection Act 1998 and the
University’s Data Protection Policy.

                                         POLICY STATEMENT

 The policy and practice of the University of Oxford require that all staff are afforded equal
 opportunities within the employment and that entry into employment with the University and
 progression within employment will be determined only by personal merit and the application of
 criteria which are related to the duties of each particular post and the relevant salary structure. In
 all cases, ability to perform the job will be the primary consideration. Subject to statutory
 provisions, no applicant or member of staff will be treated less favourably than another
 because of his or her sex, martial status, sexual orientation, racial group, or disability.

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