11 Gene Variants Associated with PD Identified

[Guest guest]

This short news article was sent to me by several local support group members.

It's about a meta-analysis of five genome-wide association studies (GWAS) done

by NIH. Prior to the study, six genetic variants had been known to increase

one's risk of getting Parkinson's Disease. After the meta-analysis, an

additional five genetic variants were identified.

This research could have implications for the LBD community as some of the

original six genetic variants were also thought to be associated with LBD and

MSA.

After the news article below, I've copied the abstract of the journal article

that appears in The Lancet. At the same link as the abstract, you can also see

the full article at no charge. (You have to register for online access.)

Robin

http://health.usnews.com/health-news/family-health/boomer-health/articles/2011/0\

2/02/scientists-id-genetic-clues-to-parkinsons

Scientists ID Genetic Clues to Parkinson's

Finding suggests DNA may play stronger role in disease than previously thought

Posted: February 2, 2011

US News 0 HealthDay News

WEDNESDAY, Feb. 2 (HealthDay News) -- Five new genetic variants believed to play

a role in Parkinson's disease have been identified by researchers.

It was long believed that Parkinson's disease was caused by environmental

factors. But since 2007, scientists have pinpointed six genetic variants that

may affect a person's risk of developing the condition. This new study brings

that to a total of 11 genetic variants.

Singleton, of the National Institute on Aging at the U.S. National

Institutes of Health in Bethesda, Md., and an international team of scientists

conducted a meta-analysis of five genome-wide association studies that were

conducted in Europe and the United States and covered about 7.7 million possible

genetic variants.

The analysis showed that 20 percent of people with the highest number of the 11

identified gene variants were 2.5 times more likely to develop Parkinson's

disease than the 20 percent of people with the least number of genetic risk

factors.

The new findings are a starting point for further research into how Parkinson's

disease develops, said the researchers.

" The identification of additional common and rare risk variants for Parkinson's

disease will probably revise our estimate of the genetic component of [the]

disease upward, " they concluded in their report.

The study was released online Feb. 2 in advance of publication in an upcoming

print issue of The Lancet.

More information

We Move has more about Parkinson's disease.

Here's the abstract and a link to the full article:

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)62345-8/fullte\

xt

The Lancet, Early Online Publication, 2 February 2011

Imputation of sequence variants for identification of genetic risks for

Parkinson's disease: a meta-analysis of genome-wide association studies

International Parkinson Disease Genomics Consortium

Summary

Background

Genome-wide association studies (GWAS) for Parkinson's disease have linked two

loci (MAPT and SNCA) to risk of Parkinson's disease. We aimed to identify novel

risk loci for Parkinson's disease.

Methods

We did a meta-analysis of datasets from five Parkinson's disease GWAS from the

USA and Europe to identify loci associated with Parkinson's disease (discovery

phase). We then did replication analyses of significantly associated loci in an

independent sample series. Estimates of population-attributable risk were

calculated from estimates from the discovery and replication phases combined,

and risk-profile estimates for loci identified in the discovery phase were

calculated.

Findings

The discovery phase consisted of 5333 case and 12 019 control samples, with

genotyped and imputed data at 7 689 524 SNPs. The replication phase consisted of

7053 case and 9007 control samples. We identified 11 loci that surpassed the

threshold for genome-wide significance (p<5×10-8). Six were previously

identified loci (MAPT, SNCA, HLA-DRB5, BST1, GAK and LRRK2) and five were newly

identified loci (ACMSD, STK39, MCCC1/LAMP3, SYT11, and CCDC62/HIP1R). The

combined population-attributable risk was 60·3% (95% CI 43·7—69·3). In the

risk-profile analysis, the odds ratio in the highest quintile of disease risk

was 2·51 (95% CI 2·23—2·83) compared with 1·00 in the lowest quintile of disease

risk.

Interpretation

These data provide an insight into the genetics of Parkinson's disease and the

molecular cause of the disease and could provide future targets for therapies.

Funding

Wellcome Trust, National Institute on Aging, and US Department of Defense.