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13-02-2011 | Neurology | Article

New genetic loci associated with PD risk uncovered

Abstract

Free abstract

MedWire News: Six genetic loci conferring risk for Parkinson's disease (PD) are confirmed and five new ones identified in a meta-analysis of genome-wide association studies (GWAS).

The discovery phase of the analysis was based on genetic data from 5333 patients with PD and 12,019 controls, and included information on more than 7 million single nucleotide polymorphisms (SNPs). The findings were confirmed in a further 7053 cases and 9007 controls.

Patients in the highest risk quintile based on their genetic profiles were 2.5-fold more likely to have PD than those in the lowest risk quintile, reports the International PD Genomics Consortium, led by Andrew Singleton (National Institutes of Health, Bethesda, Maryland, USA).

But in a linked commentary also published in The Lancet, Christine Klein and Andreas Ziegler (University of Lübeck, Germany) pointed out that the lifetime risk for PD in the general population is about 0.14%, meaning that people in the highest quintile of risk have a lifetime risk of 0.35%.

"From these calculations it becomes clear that risk prediction in an individual cannot easily be based on GWAS data," they said.

They added: "Although genetic testing for monogenic PD might be useful to minimize further work-up, clarify treatment approaches, and assist with future family planning, the clinical validity of risk SNPs is currently questionable at best.

"Thus any genetic test with risk SNPs should be strongly discouraged when there are no preventive measures or effective neuroprotective treatments."

The six confirmed risk loci in the current study are located near the genes MAPT, SNCA, HLA-DRB5, BST1, GAK, and LRRK2.

The five new loci are associated with ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R. It is biologically plausible for several of these genes to be associated with PD, say Singleton et al. For example, ACMSD is thought to affect homeostasis of quinolinic acid - a neurotoxin with a suspected role in other neurologic disorders. Experimental findings also suggest that LAMP3, HIP1R, and SYT11 could affect neuronal function.

Klein and Ziegler said that it is hard to avoid pessimism when considering the clinical relevance of such findings but noted that "the Consortium's confirmation and discovery of potentially causal SNPs for the disease hold great promise for establishing causal hypotheses."

They concluded: "With this confluence of new research leads and impressive technical advances there is good reason for optimism that these advances will be translated into direct benefits for our patients."

MedWire (www.medwire-news.md) is an independent clinical news service provided by Current Medicine Group, a trading division of Springer Healthcare Limited. © Springer Healthcare Ltd; 2011

By Eleanor McDermid

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