Navigenics #3 – “SNP testing – can it be used for disease risk assessment?”

In this third article originating from G&H’s exclusive interview with Navigenics’ Medical Director, Dr Michael Nierenberg, we explore the whole issue of SNP testing and how SNPs can be used in disease risk assessment.

Navigenics has focused on around 100 of the most definitive research papers on SNPs (single nucleotide polymorphisms) that have been most strongly associated with 18 particular diseases such as breast cancer, type II diabetes, cardiovascular disease.  The company has built an algorithm (mathematical computer program) that estimates the risk of a healthy person developing a disease if their genome has the relevant SNP. 

The company has spent immense time and financial resources on engaging its panel of scientific and clinical experts to analyze the many hundreds of SNP association studies.  Says Dr Nierenberg:  

“It is a pre-requisite for Navigenics that any SNP to be included within its core panel must have undergone rigorous scientific and clinical evaluation and had the supporting research replicated in an appropriately peer reviewed paper. Functional data and magnitude of effect are also taken into account, but studies are not automatically excluded if functional data is unavailable or the effect estimate is small.  That being said, there is currently nothing on our panel with a relative risk less than 1.1 of developing a disease if the associated SNP is carried.”

99% of human DNA sequences are the same across the entire human population.  However, variations in DNA sequence can have a major impact on how humans respond to disease, the environment and drugs & medicines. SNPs are DNA sequences that occur when a single nucleotide (A,T,C or G) in the genome sequence is altered.  For example – AAGCT to ATGCT.  For a variation to be considered a SNP, it must occur in more than 1% of the population.  Many SNPs have no effect on cell function, but many could predispose people to disease or influence their response to a drug.     

A single altered gene is only part of the disease development equation.  To be more at risk of developing a complex disease such as cardiovascular disease, an individual needs to possess a number of interactive SNP ‘faults’ in multiple genes.   

A SNP that is common in one geographical region or ethnic group, may be much rarer in another.  This is one of the main arguments against using SNP based analysis for the whole population.  For example if much of the research has been carried out on a predominantly ‘pure’ Caucasian cohort the test for that particular SNP may only be appropriate for a Caucasian and not, for example an African or Asian. 

Navigenics SNP data is largely Caucasian, but the company is more versant in the actual calculations of life-time risk and who was included in that which may well include non-Caucasians.  Dr Nierenberg explains:  

“We have reason to believe that the data applies across ethnic groups, but further data is needed to confirm this, will be collected over time, and reported to our members. For now we are very transparent about the groups in which the studies are done, whether Caucasian or in some cases non-Caucasians. Where associations have been looked for in other ethnic groups, generally we see that the effect sizes are consistent across other ethnicities including African Americans and Asians.”

As there are estimated to be over 3 million SNPs there is obviously an infinite amount of research still to be carried out on SNPs and their interaction both at the genomic and environmental levels.  The SNP single gene model is probably too simplistic to be able to provide risk scores for complex diseases, so I asked Dr Nierenberg how Navigenics foresaw their product evolving in the future. 

Dr Nierenberg advised: “We’re not basing our entire approach per se on the test, rather we’re looking at promoting wellness and the effects of the environment on health.  We believe our members should be pointed in the right direction in terms of their genetic predisposition to disease and offered suggestions on how to manage their risk.” 

In terms of the future evolution of the product, Dr Nierenberg advises that the results of ongoing studies will be added to the core test to enhance Navigenics’ service offering.

To learn more about the company and its thoughts on key issues surrounding the genomics industry, look out for the following articles which will be posted throughout this week.

Navigenics #1 – My genes, my health, my life – who are Navigenics? 

Navigenics #2 – A stroll through your genomic park – about the test

Navigenics #4 – Low penetrance v high penetrance genes

Navigenics #5 - Corporate or pragmatic genomics

Navigenics #6 – Privacy, insurance, GINA and ethics

Navigenics #7 – The barriers to success! 

Elaine Warburton  www.geneticsandhealth.com