[1] He was the eldest of three children of Martha Melba (née Burnison) and William Brown McGuffin, a merchant navy officer and Royal Naval reservist.
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.
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.
[6] 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.
[7] 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 (BPD) component of the landmark 2007 Wellcome Trust Case Control Consortium.
[9] McGuffin subsequently led genome wide searches including the GSK funded Depression Network (DeNt) sib pair linkage study across 7 European and US sites[10] and the MRC-funded first GWAS of MDD.
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.
[12] 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.
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 gene and concluded that there is true effect, with positive replication depending on use of hard, objective environmental measurements.
[15] 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.
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.
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).