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Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels


Igl, Wilmar; Johansson, Assa; Wilson, James; Wild, Sarah; Polašek, Ozren; Hayward, Caroline; Vitart, Veroniue; Hastie, Nick; Rudan, Pavao; Gnewuch, Christina et al.
Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels // Plos genetics, 6 (2010), 1. (međunarodna recenzija, članak, znanstveni)


Naslov
Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels
(Modeling of environmental effects in genome-wide association studies identifies SLC2A2 and HP as novel loci influencing serum cholesterol levels.)

Autori
Igl, Wilmar ; Johansson, Assa ; Wilson, James ; Wild, Sarah ; Polašek, Ozren ; Hayward, Caroline ; Vitart, Veroniue ; Hastie, Nick ; Rudan, Pavao ; Gnewuch, Christina ; Schmitz, Gerd ; Meitinger, Thomas ; Pramstaller, Peter ; Hicks, Andrew ; Oostra, Ben ; van Duijn, Cornelia ; Rudan, Igor ; Wright, Alan ; Campbell, Harry ; Gyllensten, Ulf ; EUROSPAN Consortium

Izvornik
Plos genetics (1553-7390) 6 (2010), 1;

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Cholesterol; SLC2A2; genome-wide association study

Sažetak
Genome-wide association studies (GWAS) have identified 38 larger genetic regions affecting classical blood lipid levels without adjusting for important environmental influences. We modeled diet and physical activity in a GWAS in order to identify novel loci affecting total cholesterol, LDL cholesterol, HDL cholesterol, and triglyceride levels. The Swedish (SE) EUROSPAN cohort (N(SE) = 656) was screened for candidate genes and the non-Swedish (NS) EUROSPAN cohorts (N(NS) = 3, 282) were used for replication. In total, 3 SNPs were associated in the Swedish sample and were replicated in the non-Swedish cohorts. While SNP rs1532624 was a replication of the previously published association between CETP and HDL cholesterol, the other two were novel findings. For the latter SNPs, the p-value for association was substantially improved by inclusion of environmental covariates: SNP rs5400 (p(SE, unadjusted) = 3.6 x 10(-5), p(SE, adjusted) = 2.2 x 10(-6), p(NS, unadjusted) = 0.047) in the SLC2A2 (Glucose transporter type 2) and rs2000999 (p(SE, unadjusted) = 1.1 x 10(-3), p(SE, adjusted) = 3.8 x 10(-4), p(NS, unadjusted) = 0.035) in the HP gene (Haptoglobin-related protein precursor). Both showed evidence of association with total cholesterol. These results demonstrate that inclusion of important environmental factors in the analysis model can reveal new genetic susceptibility loci.

Izvorni jezik
Engleski

Znanstvena područja
Javno zdravstvo i zdravstvena zaštita

Napomena
Art. no. e1000798.



POVEZANOST RADA


Projekt / tema
196-1962766-2751 - Populacijska struktura Hrvatske - antropogenetički pristup (Pavao Rudan, )
216-1080315-0302 - Odrednice zdravlja i bolesti u općoj i izoliranim ljudskim populacijama (Ozren Polašek, )

Ustanove
Medicinski fakultet, Zagreb,
Institut za antropologiju,
Medicinski fakultet, Split

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE