Julie Williams on Discovering Two Novel Susceptibility Genes for Alzheimer's Disease

New Hot Paper Commentary, January 2011

Julie Williams

Article: Genome-wide association study identifies variants at CLU and PICALM associated with Alzheimer's disease

Authors: Harold, D, et al.
Journal: NAT GENET
Volume: 41, Issue: 10, Page: 1088-U61, Year: OCT 2009
* Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales.
* Cardiff Univ, MRC, Ctr Neuropsychiat Genet & Genom, Dept Psychol Med & Neurol,Sch Med, Cardiff, S Glam, Wales.
* Kings Coll London, Natl Inst Hlth Res, Biomed Res Ctr Mental Hlth, S London & Maudsley Natl Hlth Serv Fdn Trust, London WC2R 2LS, England.
(Addresses have been truncated)

Julie Williams talks with ScienceWatch.com and answers a few questions about this month's New Hot Papers paper in the field of Molecular Biology & Genetics.

SW: Why do you think your paper is highly cited?

This paper was the first to find compelling evidence for new susceptibility genes for Alzheimer's disease, since the association with the APOE locus was published 17 years earlier.

SW: Does it describe a new discovery, methodology, or synthesis of knowledge?

We discovered two novel susceptibility genes for Alzheimer's disease; CLU and PICALM, which are now implicating new pathways to disease development. Our research built on the collaboration of over 20 research groups from Europe and the USA, to form the GERAD Consortium (Genetic and Environmental Risk in Alzheimer's Disease). This allowed us to complete a powerful genome-wide association study (GWAS) which produced genuine findings, all of which have been replicated on multiple occasions since.

SW: Would you summarize the significance of your paper in layman's terms?

"There are 820,000 people in the UK who suffer with dementia; Alzheimer's disease is the most common form."

Identifying susceptibility genes for a disease pinpoints biological pathways to disease development and in so doing, provides targets for drug and other therapies. Basically, this research can help show what is going wrong and highlight ways of putting it right.

SW: How did you become involved in this research, and how would you describe the particular challenges, setbacks, and successes that you've encountered along the way?

I originally trained as a research psychologist driven by an interest in understanding how the brain can work. Twenty years ago I was drawn to study the new area of psychiatric genetics, intrigued by the possibility that identifying genes associated with psychiatric disorders could take you to disease mechanisms, at a fine-grained molecular level.

I was lucky that this was a novel research field and I could learn the skills required, as new knowledge and techniques emerged. This is a fast-moving area where impossible experiments become feasible almost overnight. It has been an amazing journey, but it still feels as if we have only just started, there is so much needed to do.

SW: Where do you see your research leading in the future?

Since this paper was published we have identified several more susceptibility genes for Alzheimer's disease, and these results are pointing us in new directions. The immune system seems to play an important role in causing disease. Other processes implicated include the processing of lipids and neuroendocytosis.

In future we must finish what we have started and produce a more complete picture of the genetic architecture of Alzheimer's through larger GWAS and extensive sequencing. But we must also focus on understanding how the pathways implicated by genes actually contribute to disease.

SW: Do you foresee any social or political implications for your research?

There are 820,000 people in the UK who suffer with dementia; Alzheimer's disease is the most common form. It is estimated that this figure will double in the next generation. It is imperative we gain a better understanding of disease processes and potential treatments, to have a realistic chance of reducing this suffering in the future. Hopefully this research will provide a step in this direction.End

Professor Julie Williams
Professor in Neuropsychological Genetics
Cardiff University
Cardiff, Wales, UK



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