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. 2013 Oct;21(10):2099-111.
doi: 10.1002/oby.20324. Epub 2013 May 29.

QTL-based association analyses reveal novel genes influencing pleiotropy of metabolic syndrome (MetS)

Y Zhang  1 , J W Kent Jr, M Olivier, O Ali, U Broeckel, R M Abdou, T D Dyer, A Comuzzie, J E Curran, M A Carless, D L Rainwater, H H H Göring, J Blangero, A H Kissebah
Affiliations

QTL-based association analyses reveal novel genes influencing pleiotropy of metabolic syndrome (MetS)

Y Zhang et al. Obesity (Silver Spring). 2013 Oct.

Abstract

Objective: Metabolic Syndrome (MetS) is a phenotype cluster predisposing to type 2 diabetes and cardiovascular disease. We conducted a study to elucidate the genetic basis underlying linkage signals for multiple representative traits of MetS that we had previously identified at two significant QTLs on chromosomes 3q27 and 17p12.

Design and methods: We performed QTL-specific genomic and transcriptomic analyses in 1,137 individuals from 85 extended families that contributed to the original linkage. We tested in SOLAR association of MetS phenotypes with QTL-specific haplotype-tagging SNPs as well as transcriptional profiles of peripheral blood mononuclear cells (PBMCs).

Results: SNPs significantly associated with MetS phenotypes under the prior hypothesis of linkage mapped to seven genes at 3q27 and seven at 17p12. Prioritization based on biologic relevance, SNP association, and expression analyses identified two genes: insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) at 3q27 and tumor necrosis factor receptor 13B (TNFRSF13B) at 17p12. Prioritized genes could influence cell-cell adhesion and adipocyte differentiation, insulin/glucose responsiveness, cytokine effectiveness, plasma lipid levels, and lipoprotein densities.

Conclusions: Using an approach combining genomic, transcriptomic, and bioinformatic data we identified novel candidate genes for MetS.

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Figures

Figure 1
Figure 1. Genetic inter-correlation between MetS phenotypes
Heat map of pairwise genetic intercorrelation of 42 phenotypes. Colored tones represent only significant (p<0.05) correlations, red the strongest and yellow the weakest. A genetic correlation significantly different from zero suggests that the trait pair is influenced by the same gene or by genes in linkage disequilibrium. For abbreviations and units, see Table 1.
Figure 2
Figure 2. Plots of SNP associations with MetS phenotypes within QTLs at 3q27 (panel A) and 17p12 (panel B)
Dots depict levels of association of identifier phenotypes with all SNPs in the QTL region. Vertical axis represents minus logarithm of the p-values and horizontal represents the chromosomal position (kb). In panel A, LPP and IGF2BP2 are the highly prioritized genes in the 3q27 QTL region. In panel B, TNFRSF13B and HS3ST3A1 are the highly prioritized genes in the 17p12 QTL region.
See this image and copyright information in PMC

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