PuSH - Publication Server of Helmholtz Zentrum München: Genome wide meta-analysis highlights the role of genetic variation in <em>RARRES2</em> in the regulation of circulating serum chemerin.

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Tönjes, A.* ; Scholz, M.* ; Breitfeld, J.* ; Marzi, C. ; Grallert, H. ; Gross, A.* ; Ladenvall, C.* ; Schleinitz, D.* ; Krause, K.P.* ; Kirsten, H.* ; Laurila, E.* ; Kriebel, J. ; Thorand, B. ; Rathmann, W.* ; Groop, L.C.* ; Prokopenko, I.* ; Isomaa, B.* ; Beutner, F.* ; Kratzsch, J.K.* ; Thiery, J.J.* ; Faßhauer, M.* ; Klöting, N.* ; Gieger, C. ; Blüher, M.* ; Stumvoll, M.W.* ; Kovacs, P.*

Genome wide meta-analysis highlights the role of genetic variation in RARRES2 in the regulation of circulating serum chemerin.

PLoS Genet. 10:e1004854 (2015)

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Chemerin is an adipokine proposed to link obesity and chronic inflammation of adipose tissue. Genetic factors determining chemerin release from adipose tissue are yet unknown. We conducted a meta-analysis of genome-wide association studies (GWAS) for serum chemerin in three independent cohorts from Europe: Sorbs and KORA from Germany and PPP-Botnia from Finland (total N = 2,791). In addition, we measured mRNA expression of genes within the associated loci in peripheral mononuclear cells by micro-arrays, and within adipose tissue by quantitative RT-PCR and performed mRNA expression quantitative trait and expression-chemerin association studies to functionally substantiate our loci. Heritability estimate of circulating chemerin levels was 16.2% in the Sorbs cohort. Thirty single nucleotide polymorphisms (SNPs) at chromosome 7 within the retinoic acid receptor responder 2 (RARRES2)/Leucine Rich Repeat Containing (LRRC61) locus reached genome-wide significance (p<5.0×10−8) in the meta-analysis (the strongest evidence for association at rs7806429 with p = 7.8×10−14, beta = −0.067, explained variance 2.0%). All other SNPs within the cluster were in linkage disequilibrium with rs7806429 (minimum r2= 0.43 in the Sorbs cohort). The results of the subgroup analyses of males and females were consistent with the results found in the total cohort. No significant SNP-sex interaction was observed. rs7806429 was associated with mRNA expression of RARRES2 in visceral adipose tissue in women (p<0.05 after adjusting for age and body mass index). In conclusion, the present meta-GWAS combined with mRNA expression studies highlights the role of genetic variation in the RARRES2 locus in the regulation of circulating chemerin concentrations.

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