The Lancet is reporting a new study in which bioengineer Stephen Quake's entire genome was combed for clues about his various disease risks. The abstract of the Lancet article reports:
The cost of genomic information has fallen steeply, but the clinical translation of genetic risk estimates remains unclear. We aimed to undertake an integrated analysis of a complete human genome in a clinical context.
We assessed a patient with a family history of vascular disease and early sudden death. Clinical assessment included analysis of this patient's full genome sequence, risk prediction for coronary artery disease, screening for causes of sudden cardiac death, and genetic counselling. Genetic analysis included the development of novel methods for the integration of whole genome and clinical risk. Disease and risk analysis focused on prediction of genetic risk of variants associated with mendelian disease, recognised drug responses, and pathogenicity for novel variants. We queried disease-specific mutation databases and pharmacogenomics databases to identify genes and mutations with known associations with disease and drug response. We estimated post-test probabilities of disease by applying likelihood ratios derived from integration of multiple common variants to age-appropriate and sex-appropriate pre-test probabilities. We also accounted for gene-environment interactions and conditionally dependent risks.
Analysis of 2·6 million single nucleotide polymorphisms and 752 copy number variations showed increased genetic risk for myocardial infarction, type 2 diabetes, and some cancers. We discovered rare variants in three genes that are clinically associated with sudden cardiac death—TMEM43, DSP, and MYBPC3. A variant in LPA was consistent with a family history of coronary artery disease. The patient had a heterozygous null mutation in CYP2C19 suggesting probable clopidogrel resistance, several variants associated with a positive response to lipid-lowering therapy, and variants in CYP4F2 and VKORC1 that suggest he might have a low initial dosing requirement for warfarin. Many variants of uncertain importance were reported.
Although challenges remain, our results suggest that whole-genome sequencing can yield useful and clinically relevant information for individual patients.
In its report on these developments, the San Jose Mercury News notes that Quake was worried about a family history of hypertrophic cardiomyopathy. A genetic condition that causes enlarged hearts that don't beat efficiently and risk heart attacks. This specific issue caught my attention because my father had it. I have since had a 64-slice CT heart scan and I don't suffer from it. On the other hand, my 23andMe genotype scan reports that I have gene variants associated with a greater risk of experiencing atrial fibrillation. What we will all learn in the personal genome era is that if it's not one genetic flaw, it's another.