title: Genetic risk prediction in a small cohort of healthy adults in Atlanta.
abstract: Compared with single markers, polygenic scores that evaluate the joint effects of multiple trait-associated variants are more effective in explaining the variance of traits and risk of diseases. In total, 182 CHDWB (Emory-Georgia Tech Center for Health Discovery and Well Being study) adults were genotyped to investigate the common variant contributions to three traits (height, BMI, serum triglycerides) and three diseases (coronary artery disease (CAD), type 2 diabetes (T2D) and asthma). Association was contrasted between weighted and simple allelic sum polygenic scores with quantitative traits, and with the Framingham risk scores for CAD and T2D. Although the cohort size is two or three orders of magnitude smaller than typical discovery cohorts, we were able to detect significant associations and to explain up to 5% of the traits by the genetic risk scores, despite a strong influence of outliers. An unexpected finding was that CAD-associated single nucleotide polymorphisms (SNPs) explain a significant amount of the variation for total serum cholesterol. Forward step-wise sequential addition of SNPs into the regression model showed that the top-ranked SNPs explain a large proportion of variance, whereas inclusion of gender and ethnicity also affect the performance of polygenic scores.
authors: Center for Integrative Genomics, School of Biology, Georgia Institute of Technology, Atlanta, GA 30332, USA.
authors: Jing
authors: J
authors: Zhao
authors: Dalia
authors: D
authors: Arafat
authors: Kenneth L
authors: KL
authors: Brigham
authors: Greg
authors: G
authors: Gibson
mesh_terms: D000328:Adult; D000368:Aged; D001249:Asthma / Q000209:etiology*; D001827:Body Height; D015992:Body Mass Index; D002784:Cholesterol / Q000097:blood; D003324:Coronary Artery Disease / Q000209:etiology*; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology*; D005006:Ethnicity / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005845:Georgia; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D020412:Multifactorial Inheritance; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D040641:Quantitative Trait Loci; D012307:Risk Factors; D014280:Triglycerides / Q000097:blood
chemical_list: D014280:Triglycerides; D002784:Cholesterol