With a view to keeping track of enormous amount of research into the genomics of complex diseases that has arisen in the last few years, the US National Human Genome Research Institute has launched an online catalogue of published genome-wide association studies (www.genome.gov/gwastudies). The curated, searchable and publically accessible database contains information on over 350 publication, linking around 1,640 single nucleotide polymorphisms (SNPs) to more than 80 different diseases and traits.
This catalogue allows some of the trends and genomic characteristics of trait or disease associated SNPs to be analysed across multiple different publications [Hindorff LA et al. (2009) PNAS doi/10.1073], leading to a number of important insights. The effect sizes are generally small (odds ratios of less than 1.5) and, unlike genes associated with Mendelian disorders, the vast majority of genetic variation associated with complex diseases or traits lies outside of the coding regions of the genome – 45% of SNPs are located inside introns, which are located within genes but are spliced out prior to translation into functional proteins, and 43% of SNPs lie between genes. Whilst in some ways this result is unsurprising, as coding genes only account for around 1% of the genome, it is still unexpected and suggests that regulation of gene expression plays an important role in determining common traits and diseases.
Interestingly, amongst those associations that have been attributed to specific genes (which are located near the trait or disease associated SNPs), 18 regions have been linked with multiple different diseases, suggesting a common underlying aetiological pathway. For example, the major histocompatibility complex (MHC), which plays an important role in the immune system, has been implicated in 10 different conditions ranging from autoimmune disorders to lung cancer. Discoveries of a shared underlying genetic basis for different diseases are likely to become increasingly common as more gene-disease associations are uncovered, and raise a complex set of ethical implications with regards to genetic testing (see previous news).