Friday, May 04, 2007

Latest Issue of Science

The latest issue of Science has a number of interesting articles and news reports related to human genetics that are worth noting. The first is this report that a novel genetic variant that raises some people's odds of having a heart attack has been identified. The report is also the focus of this news item and this one in the Globe and Mail. Here is the abstract of the report in Science:

A Common Allele on Chromosome 9 Associated with Coronary Heart Disease
By Ruth McPherson et. al.

Coronary heart disease (CHD) is a major cause of death in Western countries. Here we used genome-wide association scanning to identify a 58 kilobase interval on chromosome 9p21 that was consistently associated with CHD in six independent samples (n> 23,000 participants) from four Caucasian populations. This interval, which is located near the CDKN2A and CDKN2B genes, contains no annotated genes and is not associated with established CHD risk factors such as plasma lipoproteins, hypertension or diabetes. Homozygotes for the risk allele comprise 20-25% of Caucasians and have a ~30-40% increased risk of CHD.

There is also this encouraging "News of the Week" report that a U.S. genetic nondiscrimination bill finally appears to be on its way to becoming law. Here is an excerpt from the report:

The House passed H.R. 493, the Genetic Information Nondiscrimination Act (GINA), on 25 April by a vote of 420 to 3. Although action on a Senate version of the bill has not yet been scheduled, the Senate unanimously passed versions of GINA in 2003 and 2005, and President George W. Bush has announced his support of the measure. The sticking point had always been in the House, where the Republican leadership, reflecting opposition from some business groups, blocked the bill from coming to a vote. With the Republicans swept out of power in the 2006 elections, the bill moved quickly to the floor and is expected to pass the Senate this month.

Advocates of the bill claim that many people are afraid to undergo genetic tests--for instance, to detect a mutation that increases risk of breast cancer--for fear that insurers or employers will discriminate against them based on that information. And a 2000 survey of genetic counselors indicated that, for the same reason, more than half would not submit charges for genetic tests to insurance companies.

And finally there is an interesting Policy Forum piece entitled "Environmental Biology and Human Disease" by David Schwartz and Francis Collins, which emphasizes the importance of paying attention to the environmental factors (and not just genetic factors) that contribute to the development of disease. This is something I also argue in my forthcoming paper "Genetic Justice Must Track Genetic Complexity". Here is an excerpt from the piece by Schwartz and Collins:

The etiology of most chronic human diseases (such as asthma, atherosclerosis, and cancer) is complex, involving a mix of genetic and environmental factors interacting with each other over hours, days, months, or years. Until recently, however, the disciplines of environmental sciences and genetics have proceeded independently; investigators in the former discipline have focused primarily on adverse conditions and diseases that are etiologically driven by environmental factors (such as benzene-induced leukemia), and those in the latter field have been finding genetic factors for highly heritable conditions (such as cystic fibrosis). Progress is now being made in identifying common genetic variations that contribute to complex diseases such as age-related macular degeneration, type 2 diabetes, and prostate cancer. However, the best opportunity to reduce risk in genetically susceptible people for the foreseeable future will not be to re-engineer their genes, but to modify their environment. The successful dietary treatment of phenyl-ketonuria is a clear example.

We need to understand how genetic factors and environmental exposures interact in individuals to alter normal biological function and to affect the risk of disease development. This basic information is critical to understanding why and under what circumstances certain individuals develop disease and others remain healthy. Defining environmental contributions is also critical in identifying how and under what circumstances DNA sequence variations affect disease pathogenesis.

....Progress in identifying genetic variations that contribute to common disease has been rapid in the last few years....[But] the same rapid rate of progress has not been achieved for precise, quantitative assays to measure environmental factors that contribute to adverse health outcomes. Certainly, assessment of environmental contributions is much more difficult than for genetic ones. The genome of an individual represents a bounded set of information, remains basically stable over time, and is very well suited to multiple analytical approaches. The potential universe of medically significant environmental exposures is much less well defined, and disease may appear several years after the exposure has ended. However, another explanation is apparent by contrasting the extensive investments in new genetic and genomic technologies over the past two decades with the much more modest expenditures in exposure sciences.