title: Presymptomatic risk assessment for chronic non-communicable diseases.
abstract: The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.
authors.affiliation: Navigenics, Foster City, California, United States of America. bpadhuka@ucdavis.edu
authors.forename: Badri
authors.initials: B
authors.lastname: Padhukasahasram
authors.forename: Eran
authors.initials: E
authors.lastname: Halperin
authors.forename: Jennifer
authors.initials: J
authors.lastname: Wessel
authors.forename: Daryl J
authors.initials: DJ
authors.lastname: Thomas
authors.forename: Elana
authors.initials: E
authors.lastname: Silver
authors.forename: Heather
authors.initials: H
authors.lastname: Trumbower
authors.forename: Michele
authors.initials: M
authors.lastname: Cargill
authors.forename: Dietrich A
authors.initials: DA
authors.lastname: Stephan
mesh_terms: D001172:Arthritis, Rheumatoid / Q000235:genetics; D002908:Chronic Disease; D003424:Crohn Disease / Q000235:genetics; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D005787:Gene Frequency; D030342:Genetic Diseases, Inborn / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D012372:ROC Curve; D015203:Reproducibility of Results; D012306:Risk; D018570:Risk Assessment