title: Genome-wide screen for metabolic syndrome susceptibility Loci reveals strong lipid gene contribution but no evidence for common genetic basis for clustering of metabolic syndrome traits.
abstract: BACKGROUND
  Genome-wide association (GWA) studies have identified several susceptibility loci for metabolic syndrome (MetS) component traits, but have had variable success in identifying susceptibility loci to the syndrome as an entity. We conducted a GWA study on MetS and its component traits in 4 Finnish cohorts consisting of 2637 MetS cases and 7927 controls, both free of diabetes, and followed the top loci in an independent sample with transcriptome and nuclear magnetic resonance-based metabonomics data. Furthermore, we tested for loci associated with multiple MetS component traits using factor analysis, and built a genetic risk score for MetS.
  
  
  RESULTS
  A previously known lipid locus, APOA1/C3/A4/A5 gene cluster region (SNP rs964184), was associated with MetS in all 4 study samples (P=7.23×10(-9) in meta-analysis). The association was further supported by serum metabolite analysis, where rs964184 was associated with various very low density lipoprotein, triglyceride, and high-density lipoprotein metabolites (P=0.024-1.88×10(-5)). Twenty-two previously identified susceptibility loci for individual MetS component traits were replicated in our GWA and factor analysis. Most of these were associated with lipid phenotypes, and none with 2 or more uncorrelated MetS components. A genetic risk score, calculated as the number of risk alleles in loci associated with individual MetS traits, was strongly associated with MetS status.
  
  
  CONCLUSIONS
  Our findings suggest that genes from lipid metabolism pathways have the key role in the genetic background of MetS. We found little evidence for pleiotropy linking dyslipidemia and obesity to the other MetS component traits, such as hypertension and glucose intolerance.
authors.affiliation: National Institute for Health and Welfare, University of Helsinki, Biomedicum, Helsinki, Finland. kati.kristiansson@thl.fi
authors.forename: Kati
authors.initials: K
authors.lastname: Kristiansson
authors.forename: Markus
authors.initials: M
authors.lastname: Perola
authors.forename: Emmi
authors.initials: E
authors.lastname: Tikkanen
authors.forename: Johannes
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authors.lastname: Kettunen
authors.forename: Ida
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authors.lastname: Surakka
authors.forename: Aki S
authors.initials: AS
authors.lastname: Havulinna
authors.forename: Alena
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authors.lastname: Stancáková
authors.forename: Chris
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authors.lastname: Barnes
authors.forename: Elisabeth
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authors.lastname: Widen
authors.forename: Eero
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authors.lastname: Kajantie
authors.forename: Johan G
authors.initials: JG
authors.lastname: Eriksson
authors.forename: Jorma
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authors.lastname: Viikari
authors.forename: Mika
authors.initials: M
authors.lastname: Kähönen
authors.forename: Terho
authors.initials: T
authors.lastname: Lehtimäki
authors.forename: Olli T
authors.initials: OT
authors.lastname: Raitakari
authors.forename: Anna-Liisa
authors.initials: AL
authors.lastname: Hartikainen
authors.forename: Aimo
authors.initials: A
authors.lastname: Ruokonen
authors.forename: Anneli
authors.initials: A
authors.lastname: Pouta
authors.forename: Antti
authors.initials: A
authors.lastname: Jula
authors.forename: Antti J
authors.initials: AJ
authors.lastname: Kangas
authors.forename: Pasi
authors.initials: P
authors.lastname: Soininen
authors.forename: Mika
authors.initials: M
authors.lastname: Ala-Korpela
authors.forename: Satu
authors.initials: S
authors.lastname: Männistö
authors.forename: Pekka
authors.initials: P
authors.lastname: Jousilahti
authors.forename: Lori L
authors.initials: LL
authors.lastname: Bonnycastle
authors.forename: Marjo-Riitta
authors.initials: MR
authors.lastname: Järvelin
authors.forename: Johanna
authors.initials: J
authors.lastname: Kuusisto
authors.forename: Francis S
authors.initials: FS
authors.lastname: Collins
authors.forename: Markku
authors.initials: M
authors.lastname: Laakso
authors.forename: Matthew E
authors.initials: ME
authors.lastname: Hurles
authors.forename: Aarno
authors.initials: A
authors.lastname: Palotie
authors.forename: Leena
authors.initials: L
authors.lastname: Peltonen
authors.forename: Samuli
authors.initials: S
authors.lastname: Ripatti
authors.forename: Veikko
authors.initials: V
authors.lastname: Salomaa
mesh_terms: D000328:Adult; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006801:Humans; D050356:Lipid Metabolism; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors