title: Identification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis.
abstract: We use whole genome sequence data and rare variant analysis methods to investigate a subset of the human serum metabolome, including 16 carnitine-related metabolites that are important components of mammalian energy metabolism. Medium pass sequence data consisting of 12,820,347 rare variants and serum metabolomics data were available on 1,456 individuals. By applying a penalization method, we identified two genes FGF8 and MDGA2 with significant effects on lysine and cis-4-decenoylcarnitine, respectively, using Δ-AIC and likelihood ratio test statistics. Single variant analyses in these regions did not identify a single low-frequency variant (minor allele count > 3) responsible for the underlying signal. The results demonstrate the utility of whole genome sequence and innovative analyses for identifying candidate regions influencing complex phenotypes.
authors.affiliation: Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Akram
authors.initials: A
authors.lastname: Yazdani
authors.affiliation: Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Azam
authors.initials: A
authors.lastname: Yazdani
authors.affiliation: Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.
authors.forename: Xiaoming
authors.initials: X
authors.lastname: Liu
authors.affiliation: Human Genetics Center, The University of Texas Health Science Center at Houston, Houston, Texas, United States of America.|Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas, United States of America.
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D015415:Biomarkers / Q000097:blood; D002331:Carnitine / Q000378:metabolism*; D005260:Female; D051524:Fibroblast Growth Factor 8 / Q000235:genetics; D058851:GPI-Linked Proteins / Q000235:genetics; D014644:Genetic Variation; D059014:High-Throughput Nucleotide Sequencing; D006801:Humans; D015810:Linkage Disequilibrium; D008239:Lysine / Q000378:metabolism; D008297:Male; D055432:Metabolomics; D008875:Middle Aged; D019006:Neural Cell Adhesion Molecules / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA
chemical_list: D015415:Biomarkers; D058851:GPI-Linked Proteins; C544522:MDGA2 protein, human; D019006:Neural Cell Adhesion Molecules; D051524:Fibroblast Growth Factor 8; D008239:Lysine; D002331:Carnitine
keywords: carnitine; linkage disequilibrium; metabolomics; penalization; rare variants