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The Actuary The magazine of the Institute & Faculty of Actuaries

A gene to remember

W here are my keys?’ I ask myself for the
third time this morning. A younger sib-
ling is performing a similar hunt with similar success. We must be related.
Is this a result of our genes, I wondered? To whom must we apportion the majority of the blame: our parents or our schoolmasters?
There is an empirical way of tackling this age-old conundrum nature vs nurture and that is the classic twin study.
I came across the study of twins as an undergraduate reading mathematics and psychology and I was given the opportunity by Tim Spector’s Twin Research Unit, made possible with funding from the Worshipful Company of Actuaries, to work in this incredibly exciting field. Behavioural genetics has striven to build bridges between psychology, psychiatry, population genetics, and molecular genetics. Leading statisticians are heavily involved, the cost of experimentation is falling, and the human genome has been laid bare. These are heady times!

Memory loss
Memory loss of some description affects us all, most notably as we age. The goals of my project are to assess the importance of genetic factors in memory and, if possible, to locate a gene or set of genes that are responsible for such functioning. This research prompts some important questions:
– Could we use pharmacological intervention to treat those who cannot function on a day-to-day basis?
– Could we identify those with possible memory deficits at an early stage?
Most psychologists agree that memory can be split into long-term and short-term memory. Long-term memory consists of what we know about the world (names and places), an autobiographical record, and what we know subconsciously (for example, hand/eye co-ordination skills). Our short-term store, or working memory, is said to consists of three components: a kind of tape-recording device which allows us to recall the beginning of a sentence so that we can understand the whole sentence as we read it; a memory sketchpad which allows us to visualise images for a few seconds; and a control centre that filters the useful bits into our long-term memory. We can also think of memory as retrospective (what I did yesterday) and prospective (I must remember to do something).

To examine the extent to which genetic factors play a role in how our memory functions, we apply the classical twin method. A comparison is made between identical or monozygotic (MZ) twins to non-identical or dizygotic (DZ) twins. MZs are genetically identical (or clones), while DZs are just like ordinary siblings who share approximately half their genes. Should our MZs show greater similarity than our DZs for a given personality trait ability to remember, say we would consider such a trait to be influenced by genes. We can estimate the influence of genes as a percentage of the genetic contribution to the differences between individuals, a measure known as heritability.
In the first study, the twins were asked to perform a series of computerised memory tasks and a reading task from which we were able to assess general and working memory, processing speed, and IQ. Genetic influences, particularly for IQ and general memory, were found to be considerable (heritabilities of 76% and 57%, respectively).

Where are my glasses?
However, memory functioning on a day-to-day basis does not involve the recall of abstract shapes and patterns: we want to know where we left our glasses or keys. By taking an established memory questionnaire and the entire twin database (around 5,000 pairs), it was possible to estimate the importance of genetic influences on everyday memory slips. We found a heritability of 45% for ‘difficulty remembering where you left your glasses or keys’.
The next step was to look for genes, using large numbers of DZ twins. The original questionnaire was expanded to include questions on prospective memory failures. The hope is to find a region or specific chromosome that has the potential to harbour a gene or set of genes for prospective memory functioning.
All this work leaves us with some challenging moral questions
– If we do manage to understand the biochemical pathways involved in our memory processes, and develop interventions, whom ought we to treat?
– Should the ‘worried well’ benefit from such research?
– If we can readily identify those susceptible to poor memory functioning or early decline, who should be told and what can they do with that information?
– Should schools attempt streaming by genotype?
– Could employers let someone go aged 523/4 (‘Sorry Mr Wilkins but we’ve seen your DNA and this time next Tuesday, you won’t know your hat from your wife’)?
– Should insurance companies be able to call for genetic information to try to avoid future adverse selection?
These are questions for our society and government to debate now and into the future for the health of the entire nation. For those with dementia and Alzheimer’s disease, the questions are more immediate, and the call for a miracle drug is more pressing. We have seen remarkable progress in behavioural genetics in recent years, but surely this is only just the beginning