Peter McGuffin (04 February 1949 – 30 January 2024) was a Northern Irish
psychiatrist
A psychiatrist is a physician who specializes in psychiatry. Psychiatrists are physicians who evaluate patients to determine whether their symptoms are the result of a physical illness, a combination of physical and mental ailments or strictly ...
and
geneticist
A geneticist is a biologist or physician who studies genetics, the science of genes, heredity, and variation of organisms. A geneticist can be employed as a scientist or a lecturer. Geneticists may perform general research on genetic process ...
from
Belfast
Belfast (, , , ; from ) is the capital city and principal port of Northern Ireland, standing on the banks of the River Lagan and connected to the open sea through Belfast Lough and the North Channel (Great Britain and Ireland), North Channel ...
.
Early life
Peter McGuffin was born in Belfast, Northern Ireland on 14 February 1949.
He was the eldest of three children of Martha Melba (née Burnison) and William Brown McGuffin, a merchant navy officer and Royal Naval reservist. The family moved to the Isle of Wight in 1959 when William was appointed a Trinity House Pilot for the Port of Southampton.
Education and career summary
McGuffin entered Isle of Wight's Sandown Grammar School at age 10. At age 15 he made an early career choice, deciding to become a psychiatrist after coming across Freud's
Introductory Lectures on Psychoanalysis in the local public library at
Ryde
Ryde is an English seaside town and civil parish on the north-east coast of the Isle of Wight. The built-up area had a population of 24,096 according to the 2021 Census. Its growth as a seaside resort came after the villages of Upper Ryde and ...
. He attended medical school at the
University of Leeds
The University of Leeds is a public research university in Leeds, West Yorkshire, England. It was established in 1874 as the Yorkshire College of Science. In 1884, it merged with the Leeds School of Medicine (established 1831) and was renamed Y ...
, where he graduated in 1972 and then received postgraduate training in
internal medicine
Internal medicine, also known as general medicine in Commonwealth nations, is a medical specialty for medical doctors focused on the prevention, diagnosis, and treatment of diseases in adults. Its namesake stems from "treatment of diseases of ...
. At this stage, he became interested in genetics and had his first publications on
immunogenetic aspects of
coronary heart disease
Coronary artery disease (CAD), also called coronary heart disease (CHD), or ischemic heart disease (IHD), is a type of cardiovascular disease, heart disease involving Ischemia, the reduction of blood flow to the cardiac muscle due to a build-up ...
.
While he and his wife
Anne Farmer were still junior doctors in Leeds, he transitioned this interest to psychiatric disorders and carried out one of the first genetic marker association studies on
schizophrenia
Schizophrenia () is a mental disorder characterized variously by hallucinations (typically, Auditory hallucination#Schizophrenia, hearing voices), delusions, thought disorder, disorganized thinking and behavior, and Reduced affect display, f ...
. This research suggested an association between the HLA system and the disorder, which was subsequently confirmed 36 years later by a genome-wide association study, led by one of McGuffin's former PhD students
Michael C. O'Donovan.
McGuffin completed his training as a psychiatrist at the
Maudsley Hospital
The Maudsley Hospital is a British psychiatric hospital in south London. The Maudsley is the largest mental health training institution in the UK. It is part of South London and Maudsley NHS Foundation Trust, and works in partnership with the I ...
,
London
London is the Capital city, capital and List of urban areas in the United Kingdom, largest city of both England and the United Kingdom, with a population of in . London metropolitan area, Its wider metropolitan area is the largest in Wester ...
and was awarded a
Medical Research Council Fellowship to study genetics at the
University of London
The University of London (UoL; abbreviated as Lond or more rarely Londin in Post-nominal letters, post-nominals) is a collegiate university, federal Public university, public research university located in London, England, United Kingdom. The ...
and at
Washington University in St. Louis
Washington University in St. Louis (WashU) is a private research university in St. Louis, Missouri, United States. Founded in 1853 by a group of civic leaders and named for George Washington, the university spans 355 acres across its Danforth ...
, where he spent a formative 18 months under the mentorship of 'Ted'
Theodore Reich and
Irving Gottesman. He completed a PhD with a thesis describing one of the first multi-marker genetic linkage studies in schizophrenia. He then became an MRC Senior Clinical Fellow at the Maudsley and the
Institute of Psychiatry
The Institute of Psychiatry, Psychology & Neuroscience (IoPPN) is a centre for mental health and neuroscience research, education and training in Europe. It is dedicated to understanding, preventing and treating mental illness, neurological co ...
(now part of
King's College London
King's College London (informally King's or KCL) is a public university, public research university in London, England. King's was established by royal charter in 1829 under the patronage of George IV of the United Kingdom, King George IV ...
) and then took up the Chair of Psychological Medicine at the
University of Wales
The University of Wales () is a confederal university based in Cardiff, Wales. Founded by royal charter in 1893 as a federal university with three constituent colleges – Aberystwyth, Bangor and Cardiff – the university was the first universit ...
College of Medicine in
Cardiff
Cardiff (; ) is the capital city, capital and List of urban areas in the United Kingdom, largest city of Wales. Cardiff had a population of in and forms a Principal areas of Wales, principal area officially known as the City and County of Ca ...
in 1987. He subsequently established the Cardiff department as one of the World's leading centres for psychiatric genetic research, and was among the early pioneers of multi-centre international collaborations in psychiatric genetics such as the
European Science Foundation
The European Science Foundation (ESF) is an association of 11 member organizations devoted to scientific research in 8 European countries. ESF is an independent, non-governmental, non-profit organization that promotes science in Europe. It was e ...
programme on the Molecular Neurobiology of Mental Illness (MNMI).
He moved back to London as successor to Prof Sir
Michael Rutter
Sir Michael Llewellyn Rutter (15 August 1933 – 23 October 2021) was the first person to be appointed professor of child psychiatry in the United Kingdom. He has been described as the "father of child psychiatry".
Rutter was professor of de ...
as Director of the MRC Social, Genetic and Developmental Psychiatry Centre at the Institute of Psychiatry in October 1998. From January 2007 to December 2009, he was the Dean of the Institute of Psychiatry. He was elected a founder Fellow of the
Academy of Medical Sciences
The Academy of Medical Sciences is an organisation established in the UK in 1998. It is one of the four UK National Academy, National Academies, the others being the British Academy, the Royal Academy of Engineering and the Royal Society.
Its ...
in 1998. Despite his very early Freudian leanings, McGuffin's research and publications have mainly focused on the genetics of normal and abnormal behaviour.
Contributions to research
Linkage and association
As a junior doctor Peter McGuffin carried out one of the earliest allelic association studies in psychiatry. This implicated the major histocompatibility complex (
MHC) in schizophrenia. He subsequently performed a meta-analysis of his and four other studies of HLA-schizophrenia association showing highly significant results. The MHC association was eventually confirmed by genome wide association studies (
GWAS GWAS may refer to:
*Genome-wide association study, study of mutations' correlations with disease or other phenotypic expressions
*''gwas'', a Welsh term for a valet
* Great Western Ambulance Service, the ambulance service serving Somerset, Gloucest ...
) more than 30 years later. He went on to perform the first family linkage study of schizophrenia that used multiple classical markers and applied plausible parametric models as well as non-parametric analysis.
This formed the basis of his PhD in which he also performed power analyses demonstrating that very much larger sample sizes would be necessary to identify responsible loci in disorders such as schizophrenia using linkage because of incomplete penetrance. To this end McGuffin, with his colleague
Roger Marchbanks, wrote a proposal to the European Science Foundation (ESF) that led to the multi centre network, then programme, on MNMI. The MNMI ran from 1987–96 and brought together 14 ESF member organisations including the MRC. It kickstarted molecular psychiatric genetics in Europe and inspired the setting up of a parallel multicentre collaboration in the US under
NIMH
NIMH may refer to:
* Nickel–metal hydride battery (NiMH), a type of electrical battery
*National Institute of Mental Health, an agency of the United States government
* National Institute of Medical Herbalists, a professional organisation in the ...
.
A solution to the problem of establishing diagnostic standardisation and reliability across the European and US collaborations was provided by the computerised OPCRIT system.
OPCRIT showed good reliability across European and US sites and has continued to be used frequently in genetic and epidemiological studies including the
bipolar disorder
Bipolar disorder (BD), previously known as manic depression, is a mental disorder characterized by periods of Depression (mood), depression and periods of abnormally elevated Mood (psychology), mood that each last from days to weeks, and in ...
(BPD) component of the landmark 2007
Wellcome Trust Case Control Consortium.
Long before it was technically achievable, McGuffin was an advocate of aiming to scan the entire genome for genes involved in the common disorders such as schizophrenia, BPD and
major depressive disorder
Major depressive disorder (MDD), also known as clinical depression, is a mental disorder characterized by at least two weeks of pervasive depression (mood), low mood, low self-esteem, and anhedonia, loss of interest or pleasure in normally ...
(MDD), bearing in mind that they likely involved several, perhaps many, genes. This was also likely to be the case for quantitative behavioural traits such as
cognitive ability
Cognitive skills are skills of the mind, as opposed to other types of skills such as motor skills, social skills or life skills. Some examples of cognitive skills are literacy, self-reflection, logical reasoning, abstract thinking, critical th ...
. The principles were set out in an influential review with
Plomin and
Owen
Owen may refer to:
People and fictional characters
* Owen (name), including a list of people and fictional characters with the given name or surname
Places United States
* Owen, Missouri, a ghost town
* Owen, Wisconsin
* Owen County, Indiana
...
which pointed out that linkage was appropriate for detection of quantitative trait loci (QTLs) or polygenes contributing comparatively large amounts of variance (~10%) whereas association can detect small effects (1% or less). At this stage genome wide linkage was becoming feasible but GWAS was still a dream. The alternative association approach was a focus on candidate genes that encode for proteins with a plausible aetiological role. An example was the
5-HT2a receptor
The 5-HT2A receptor is a subtype of the 5-HT2 receptor, 5-HT2 receptor that belongs to the serotonin receptor family and functions as a GPCR, G protein-coupled receptor (GPCR). It is a cell surface receptor that activates multiple intracellular ...
gene found to be schizophrenia associated by EMASS (EU funded, PI McGuffin), the first multicentre candidate gene association study of its type.
McGuffin subsequently led genome wide searches including the
GSK funded Depression Network (DeNt) sib pair linkage study across 7 European and US sites
and the MRC-funded first GWAS of MDD.
As with other disorders, these initial genome wide searches pointed to the need for vastly larger sample sizes, and so McGuffin’s group pooled resources with others forming the
Psychiatric Genomics Consortium which has gone onto to identify multiple genome wide significant ‘hits’ in BPD, MDD as well as in schizophrenia,
autism
Autism, also known as autism spectrum disorder (ASD), is a neurodevelopmental disorder characterized by differences or difficulties in social communication and interaction, a preference for predictability and routine, sensory processing d ...
and
ADHD
Attention deficit hyperactivity disorder (ADHD) is a neurodevelopmental disorder characterised by symptoms of inattention, hyperactivity, impulsivity, and emotional dysregulation that are excessive and pervasive, impairing in multiple ...
. By sharing genome wide data McGuffin’s group have also participated in successful searches in other disorders including
motor neuron disease
Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease (MND) or—in the United States—Lou Gehrig's disease (LGD), is a rare, terminal neurodegenerative disorder that results in the progressive loss of both upper and low ...
and eye disease.
Gene-Environment (GE) Interplay
In 1982 McGuffin became the first psychiatrist to be awarded an MRC senior clinical fellowship. This was to carry out a novel family study of index cases with or without serious adversity in the form of threatening life events before the onset of MDD and their relatives. Contrary to the widely held clinical view at that time that depression could be divided into reactive and endogenous forms, there was no difference in the frequency of depression in relatives whether or not the index cases had an illness precipitated by adversity. Nor was there any correspondence between clinical symptom pattern and familiality. Furthermore, the frequency of reported life events among relatives of index cases was markedly higher than that in the general population raising the issue that both adversity and depression were familial.
These findings were viewed as controversial at the time challenging the idea that it was possible to separate threatening events that arise “out of the blue” from those that are dependent on an individual’s behaviour. McGuffin followed up the Camberwell findings in a study in Cardiff that compared subjects with and without onset depression and their nearest age siblings. In a series of publications McGuffin and Farmer tested the alternative hypotheses that the familial overlap between depression and life events reflected either a hazard prone lifestyle or a tendency to over perceive adversity or simply a tendency for adverse events to be shared by relatives. The findings suggested that all three types of explanation played a part and the lifestyle or cognitive components were significantly influenced by personality factors.
This was in keeping with work by McGuffin and Thapar that self reported life events in adolescents have a heritable component whereas parent reported events in the same subjects do not. The genetic contribution to self reported events was subsequently confirmed by Robert Power, one of McGuffin’s PhD students, by estimating GWAS-derived SNP heritability.
On a related theme, one of the most controversial areas in 21st century behavioural genetics has concerned attempts to explore GE interactions with specific brain expressed genes, much of the original work coming from other groups in the McGuffin led MRC SGDP Centre. Uher and McGuffin have scrutinized the world data for a functional polymorphism in the promoter of the
serotonin transporter
The serotonin transporter (SERT or 5-HTT) also known as the sodium-dependent serotonin transporter and solute carrier family 6 member 4 is a protein that in humans is encoded by the SLC6A4 gene. SERT is a type of monoamine transporter protein t ...
gene and concluded that there is true effect, with positive replication depending on use of hard, objective environmental measurements.
This is in keeping with McGuffin’s earlier findings that more subjective reports of adversity are influenced by personality/heritable factors.
Twin studies
McGuffin and colleagues re-examined the classic Maudsley schizophrenia study of Gottesman and Shields at a time when there widespread questioning of a genetic component for schizophrenia on the basis that studies until then had used descriptive clinical diagnoses rather than modern operational criteria. It was found that, far from reducing genetic evidence, the application of explicit and reliable modern criteria indicated high heritability.
Subsequently the recently introduced
DSM III criteria were scrutinized and found to be valid in that, when applied strictly and excluding broader phenotypes, they defined a highly heritable syndrome.
Further studies using an extended Maudsley twin register series estimated heritability of related psychotic syndromes using
structural equation models
Structural equation modeling (SEM) is a diverse set of methods used by scientists for both observational and experimental research. SEM is used mostly in the social and behavioral science fields, but it is also used in epidemiology, business, ...
(SEM)
and also showed that the genetic components of schizophrenia and BPD overlap as well as having specific components distinct to each syndrome.
This was thought highly controversial at the time but has now been borne out by other studies including GWAS. Turning to mood disorders it was shown with SEM that both clinically ascertained and operationally defined MDD and BPD are substantially heritable with both overlapping and syndrome-specific components.
Again, this has now been confirmed by GWAS.
Until the 1990s genetic data on childhood psychiatric disorders were scant. With his then MRC fellow
Anita Thapar, McGuffin launched a systematically ascertained Cardiff twin register. Among their early findings were that depressive symptomatology before adult life is influenced by genetic factors. More specifically, genetic effects were especially important in adolescence, whereas shared environmental effects account for most of the variation among children in the 8-11 age group,
a pattern that has subsequently been replicated elsewhere. They were also among the first to establish the heritability of ADHD, and that severe ADHD with conduct problems is especially heritable.
Pharmacogenomics
The EU funded GENDEP study is a multi-site investigation that used animal, ''in vitro'' and human studies to investigate predictors of antidepressant response. The first of its kind, the partly randomized human study of two drugs with differing modes of action (serotinergic and noradrenergic) produced suggestive
GWAS GWAS may refer to:
*Genome-wide association study, study of mutations' correlations with disease or other phenotypic expressions
*''gwas'', a Welsh term for a valet
* Great Western Ambulance Service, the ambulance service serving Somerset, Gloucest ...
results
and highly significant findings with an inflammatory marker (high sensitivity
CRP) that appears to be state dependent.
The GENDEP study, along with other GWAS related studies, has generated vast amounts of clinical and ‘omics’ data. With psychiatry now entering a big data era, McGuffin and colleagues developed machine learning and AI related approaches as a practical solution to big data analysis.
Personal life and death
McGuffin met
Anne Farmer at medical school in Leeds and they married on graduation in 1972. She subsequently became an academic psychiatrist and they published many papers together. They had three children.
Peter McGuffin died on 30 January 2024, at the age of 74.
Awards
McGuffin was elected Fellow of the
Royal College of Physicians of London
The Royal College of Physicians of London, commonly referred to simply as the Royal College of Physicians (RCP), is a British professional membership body dedicated to improving the practice of medicine, chiefly through the accreditation of ph ...
in 1988 and
Fellow of the Royal College of Psychiatrists in 1989 and became a founder Fellow of the
Academy of Medical Sciences
The Academy of Medical Sciences is an organisation established in the UK in 1998. It is one of the four UK National Academy, National Academies, the others being the British Academy, the Royal Academy of Engineering and the Royal Society.
Its ...
in 1998.
Other honours include Lifetime Achievement Awards from the International Society for Psychiatric Genetics (2007) and King's College London (2012) and an Honorary Fellowship from Cardiff University (2008).
He was appointed Commander of the Order of the British Empire (CBE) in the 2016 Birthday Honours for services to biomedical research and psychiatric genetics. He served as the second president of the
International Society of Psychiatric Genetics (1996-2000) .
Publications
McGuffin published more than 500 papers and is one of the 3000 or so researchers who, according to Google Scholar, has an H index of more than 100.
*''Behavioral Genetics in the Postgenomic Era'', by
Robert Plomin,
John C. DeFries, Ian W. Craig, and Peter McGuffin
*''Behavioral Genetics'' by John C. DeFries, Peter McGuffin,
Gerald E. McClearn
Gerald "Jerry" McClearn (July 28, 1927 – January 5, 2017) was an American Behavioral genetics, behavior geneticist and professor emeritus of health and human development and biobehavioral health at the Pennsylvania State University.
Education
M ...
, and Robert Plomin
*''Beyond Nature and Nurture in Psychiatry'', by James MacCabe, Owen O'Daly,
Robin Murray, and Peter McGuffin
*''Psychiatric Genetics and Genomics'', by Peter McGuffin,
Michael J. Owen, and
Irving I. Gottesman
*''Measuring Psychopathology'', by Anne Farmer, Peter McGuffin, and Julie Williams
*''The New Genetics of Mental Illness'', by Peter McGuffin and Robin Murray
*''Schizophrenia: The Major Issues'', by Paul Bebbington and Peter McGuffin
*''The Essentials of Psychiatry'', by Robin Murray,
Ken Kendler, Peter McGuffin, and
Simon Wessely
Sir Simon Charles Wessely (born 23 December 1956) is a British psychiatrist. He is Regius Professor of Psychiatry at the Institute of Psychiatry, King's College London and head of its department of psychological medicine, vice dean for academi ...
References
* Schizophrenia Working Group of the Psychiatric Genomics Consortium. Epub 2014 Jul 22
{{DEFAULTSORT:McGuffin, Peter
1949 births
2024 deaths
20th-century British medical doctors
21st-century British medical doctors
British psychiatrists
Geneticists from Northern Ireland
Psychiatric geneticists
Alumni of the University of London
Alumni of the University of Leeds
Alumni of the University of Wales
Washington University in St. Louis alumni
Fellows of the Academy of Medical Sciences (United Kingdom)
Academics of King's College London
Fellows of King's College London
Commanders of the Order of the British Empire
Health professionals from Belfast
Presidents of the International Society of Psychiatric Genetics