biostudies-literatureYazdani AUniversity of Texas Health Science Center at HoustonNHLBI NIH HHSNational Heart, Lung, and Blood InstituteNHGRI NIH HHSNational Institutes of Health contractNational Institutes of HealthNational Heart, Lung, and Blood Institute contractsNational Human Genome Research InstituteNational Human Genome Research Institute contract486-91https://www.ebi.ac.uk/biostudies/studies/S-EPMC5609480biostudies-literatureUnknown40(6)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 foGenetic epidemiologyIdentification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis.PMC5609480RC2 HL102419U01 HG004402HHSN268201100011IU54 HG003273HL102419U54 HG006542R01 HL059367HHSN268201100009IHHSN268201100005CUM1 HG006542HHSN268201100007CHG004402HHSN268201100009CHHSN268201100011CHHSN268201100005IR01HL087641HHSN268201100007IHHSN268201100005GR01HL086694HHSN268200625226CHG006542HG003273HHSN268201100006CR01HL59367HHSN268201100008CU01HG004402HHSN268201100010CHHSN268201100008IR01 HL086694HHSN268201100012CR01 HL087641Liu XYazdani ABoerwinkle EfalseIdentification of Rare Variants in Metabolites of the Carnitine Pathway by Whole Genome Sequencing Analysis.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 fo2016-01-01T00:00:00Z2016 Sep2025-04-25T18:19:50.957Z2019-06-06T18:09:32ZS-EPMC56094802725658110.1002/gepi.21980