Gene-environment interactions would be focus of NIH-led effort | By W

[Guest guest]

A 500,000-person study?

Gene-environment interactions would be focus of NIH-led effort | By W

The National Institutes of Health (NIH) is considering undertaking the

largest population-based study ever done in the United States. NIH issued a

request for information (RFI) from researchers earlier this month about the

questions a large cohort study on the gene­environment interactions involved

in common human diseases might ask, and how the study might be constructed.

A project of this kind is " the logical next step beyond the mapping of the

human genome and doing case studies, " said Terri Manolio, director of the

National Heart, Lung, and Blood Institute's epidemiology and biometry

program.

Such a project would try to survey a representative sample of the US

population, explained Manolio, and may include as many as 500,000

participants from all geographic, racial, ethnic, and socioeconomic groups

defined in the most recent US census. No funds have been appropriated for

the project yet, and NIH officials are hesitant to speculate on how much it

might cost.

Manolio said that NIH officials hope to find a way to incorporate data from

previously conducted studies of individual diseases. " We want to include

existing cohorts, " she said, " but we have to decide, how feasible is it to

add on to these disease studies? "

Alan Guttmacher, deputy director of the National Human Genome Research

Institute (NHGRI), said that while there are questions about how the

genotyping should be done‹for example, whether it should all be done at once

or if it should wait until the technology improves‹identifying the

environmental factors on which the study should focus, such as diet,

lifestyle, and geographic area, might be the real challenge. " We don't have

the expertise or the imagination to come up with all the hypotheses we want

to answer with this data, " he told The Scientist.

While the project could be likened to the UK BioBank and Iceland's deCODE

Genetics, Guttmacher said, its objectives and approach would not be exactly

the same. " The general idea is not dissimilar, " he said, " but how we get

there... would be different. " For example, many of the minority ethnic

groups that should be included in a US study are not present at all in the

United Kingdom.

So far, the response from the research community has been generally

positive, Manolio told The Scientist. " People are aware that there is room

for something like this, " Guttmacher said, adding that he has been " quite

impressed " by the fact that scientists involved in similar research seem

excited rather than threatened by the idea of this study.

" We know that a lot of genes contribute to [disease] risk, but aren't the

only factor involved, " said Terri Beaty, an epidemiologist at the s

Hopkins University Bloomberg School of Public Health. A study of this kind

could be " potentially very useful, " she said, especially if we ever hope to

attain the reality of personalized medicine.

NIH officials are unsure about how long the planning phase will last, how

soon the project will get underway, and how soon it will start providing

meaningful information. " Ideally, we will get useful data a few years into

the study, but still be mining for information decades [later], " said

Guttmacher. He said that a paper by NHGRI director Francis

explaining the benefits of such a study would be appearing in a major

research journal later this week.

Although the official RFI closes this Friday (May 28), Guttmacher stressed

that discussion of the project would be ongoing. Guttmacher said that the

project, if initiated, would involve researchers from federal, academic, and

private institutes, and that community involvement would also be a large

component. NIH hopes to make as much as of the information freely available

to the public as possible, which will require strict privacy guidelines.

NIH recognizes that a project of this magnitude would " cost a lot and take a

long time, " said Guttmacher, " but if you can't do it well, it's not worth

doing... We're really trying to have the science design this study [and]

drive the budget. "

Beaty agreed: " It has a lot of potential, it needs to be done, and it needs

to be done well, " she told The Scientist.

Links for this article

" Request for information: design and implementation of a large-scale

prospective cohort study of genetic and environmental influences on common

diseases, " National Institutes of Health press release, May 5, 2004.

http://grants.nih.gov/grants/guide/notice-files/NOT-OD-04-041.h tml 

T.M. Powledge, " Human genome project complete, " The Scientist, April 15,

2003.

http://www.biomedcentral.com/news/20030415/03 

National Heart, Lung, and Blood Institute: Division of Epidemiology and

Clinical Applications

http://www.nhlbi.nih.gov/about/deca/ 

Alan Guttmacher

http://www.genome.gov/10005495 

P. Hagan, " UK Biobank reveals ethics framework, " The Scientist, September

24, 2003.

http://www.biomedcentral.com/news/20030924/03/ 

Terri Beaty

http://faculty.jhsph.edu/?F=Terri&L=Beaty