Clinical assessment incorporating a personal genome

摘要: Summary Background The cost of genomic information has fallen steeply, but the clinical translation genetic risk estimates remains unclear. We aimed to undertake an integrated analysis a complete human genome in context. Methods assessed patient with family history vascular disease and early sudden death. Clinical assessment included this patient's full sequence, prediction for coronary artery disease, screening causes cardiac death, counselling. Genetic development novel methods integration whole risk. Disease focused on variants associated mendelian recognised drug responses, pathogenicity variants. queried disease-specific mutation databases pharmacogenomics identify genes mutations known associations response. estimated post-test probabilities by applying likelihood ratios derived from multiple common age-appropriate sex-appropriate pre-test probabilities. also accounted gene-environment interactions conditionally dependent risks. Findings Analysis 2·6 million single nucleotide polymorphisms 752 copy number variations showed increased myocardial infarction, type 2 diabetes, some cancers. discovered rare three that are clinically death— TMEM43, DSP , MYBPC3 . A variant LPA was consistent disease. had heterozygous null CYP2C19 suggesting probable clopidogrel resistance, several positive response lipid-lowering therapy, CYP4F2 VKORC1 suggest he might have low initial dosing requirement warfarin. Many uncertain importance were reported. Interpretation Although challenges remain, our results whole-genome sequencing can yield useful relevant individual patients. Funding National Institute General Medical Sciences; Heart, Lung And Blood Institute; Human Genome Research Howard Hughes Library Medicine, Lucile Packard Foundation Children's Health; Hewlett Foundation; Breetwor Family Foundation.