DESCRIPTION:

List of positional candidate genes after correcting for multiple testing and controlling the false discovery rate from genome wide association studies (GWAS) retrieved from the NHGRI-EBI Catalog of published genome-wide association studies (http://www.ebi.ac.uk/gwas/). The disease/trait examined in this study, as reported by the authors, was Lipid traits. The EFO term total cholesterol measurement was annotated to this set after curation by NHGRI-EBI. Intergenic SNPS were mapped to both the upstream and downstream gene. P-value uploaded. This gene set was generated using gwas2gs v. 0.1.8 and the GWAS Catalog v. 1.0.1.

LABEL:

GWAS: total cholesterol measurement

SCORE TYPE:

P-Value

DATE ADDED:

2017-05-02

DATE UPDATED:

2024-04-25

SPECIES:

AUTHORS:

I Surakka, A Isaacs, LC Karssen, PP Laurila, RP Middelberg, E Tikkanen, JS Ried, C Lamina, M Mangino, W Igl, JJ Hottenga, V Lagou, P van der Harst, I Mateo Leach, T Esko, Z Kutalik, NW Wainwright, MV Struchalin, AP Sarin, AJ Kangas, JS Viikari, M Perola, T Rantanen, AK Petersen, P Soininen, A Johansson, N Soranzo, AC Heath, T Papamarkou, I Prokopenko, A Tönjes, F Kronenberg, A Döring, F Rivadeneira, GW Montgomery, JB Whitfield, M Kähönen, T Lehtimäki, NB Freimer, G Willemsen, EJ de Geus, A Palotie, MS Sandhu, DM Waterworth, A Metspalu, M Stumvoll, AG Uitterlinden, A Jula, G Navis, C Wijmenga, BH Wolffenbuttel, MR Taskinen, M Ala-Korpela, J Kaprio, KO Kyvik, DI Boomsma, NL Pedersen, U Gyllensten, JF Wilson, I Rudan, H Campbell, PP Pramstaller, TD Spector, JC Witteman, JG Eriksson, V Salomaa, BA Oostra, OT Raitakari, HE Wichmann, C Gieger, MR Järvelin, NG Martin, A Hofman, MI McCarthy, L Peltonen, CM van Duijn, YS Aulchenko, S Ripatti

TITLE:

A genome-wide screen for interactions reveals a new locus on 4p15 modifying the effect of waist-to-hip ratio on total cholesterol.

JOURNAL:

PLoS genetics Oct 2011, Vol 7, pp. e1002333

ABSTRACT:

Recent genome-wide association (GWA) studies described 95 loci controlling serum lipid levels. These common variants explain ∼25% of the heritability of the phenotypes. To date, no unbiased screen for gene-environment interactions for circulating lipids has been reported. We screened for variants that modify the relationship between known epidemiological risk factors and circulating lipid levels in a meta-analysis of genome-wide association (GWA) data from 18 population-based cohorts with European ancestry (maximum N = 32,225). We collected 8 further cohorts (N = 17,102) for replication, and rs6448771 on 4p15 demonstrated genome-wide significant interaction with waist-to-hip-ratio (WHR) on total cholesterol (TC) with a combined P-value of 4.79×10(-9). There were two potential candidate genes in the region, PCDH7 and CCKAR, with differential expression levels for rs6448771 genotypes in adipose tissue. The effect of WHR on TC was strongest for individuals carrying two copies of G allele, for whom a one standard deviation (sd) difference in WHR corresponds to 0.19 sd difference in TC concentration, while for A allele homozygous the difference was 0.12 sd. Our findings may open up possibilities for targeted intervention strategies for people characterized by specific genomic profiles. However, more refined measures of both body-fat distribution and metabolic measures are needed to understand how their joint dynamics are modified by the newly found locus. PUBMED: 22028671
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