title: A genome-wide perspective of genetic variation in human metabolism.
abstract: Serum metabolite concentrations provide a direct readout of biological processes in the human body, and they are associated with disorders such as cardiovascular and metabolic diseases. We present a genome-wide association study (GWAS) of 163 metabolic traits measured in human blood from 1,809 participants from the KORA population, with replication in 422 participants of the TwinsUK cohort. For eight out of nine replicated loci (FADS1, ELOVL2, ACADS, ACADM, ACADL, SPTLC3, ETFDH and SLC16A9), the genetic variant is located in or near genes encoding enzymes or solute carriers whose functions match the associating metabolic traits. In our study, the use of metabolite concentration ratios as proxies for enzymatic reaction rates reduced the variance and yielded robust statistical associations with P values ranging from 3 x 10(-24) to 6.5 x 10(-179). These loci explained 5.6%-36.3% of the observed variance in metabolite concentrations. For several loci, associations with clinically relevant parameters have been reported previously.
authors.affiliation: Institute of Epidemiology, Helmholtz Zentrum München, German Research Center for Environmental Health, Neuherberg, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Illig
authors.forename: Christian
authors.initials: C
authors.lastname: Gieger
authors.forename: Guangju
authors.initials: G
authors.lastname: Zhai
authors.forename: Werner
authors.initials: W
authors.lastname: Römisch-Margl
authors.forename: Rui
authors.initials: R
authors.lastname: Wang-Sattler
authors.forename: Cornelia
authors.initials: C
authors.lastname: Prehn
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Altmaier
authors.forename: Gabi
authors.initials: G
authors.lastname: Kastenmüller
authors.forename: Bernet S
authors.initials: BS
authors.lastname: Kato
authors.forename: Hans-Werner
authors.initials: HW
authors.lastname: Mewes
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Martin Hrabé
authors.initials: MH
authors.lastname: de Angelis
authors.forename: Florian
authors.initials: F
authors.lastname: Kronenberg
authors.forename: Nicole
authors.initials: N
authors.lastname: Soranzo
authors.forename: H-Erich
authors.initials: HE
authors.lastname: Wichmann
authors.forename: Tim D
authors.initials: TD
authors.lastname: Spector
authors.forename: Jerzy
authors.initials: J
authors.lastname: Adamski
authors.forename: Karsten
authors.initials: K
authors.lastname: Suhre
mesh_terms: D000090943:Delta-5 Fatty Acid Desaturase; D056426:Genetic Loci / Q000235:genetics; D014644:Genetic Variation; D015894:Genome, Human / Q000235:genetics*; D055106:Genome-Wide Association Study; D006801:Humans; D055442:Metabolome / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results; D006113:United Kingdom