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

ABSTRACT: 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.

SUBMITTER: Tonjes A

PROVIDER: S-EPMC4270463 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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

Tönjes Anke A Scholz Markus M Breitfeld Jana J Marzi Carola C Grallert Harald H Gross Arnd A Ladenvall Claes C Schleinitz Dorit D Krause Kerstin K Kirsten Holger H Laurila Esa E Kriebel Jennifer J Thorand Barbara B Rathmann Wolfgang W Groop Leif L Prokopenko Inga I Isomaa Bo B Beutner Frank F Kratzsch Jürgen J Thiery Joachim J Fasshauer Mathias M Klöting Nora N Gieger Christian C Blüher Matthias M Stumvoll Michael M Kovacs Peter P

PLoS genetics 20141218 12

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 ...[more]

PMID: 25521368

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Project description:A previous study in cattle based on >48,000 markers identified markers on chromosome 4 near the chemerin gene associated with average daily feed intake (ADFI) in steers (P < 0.008). Chemerin is an adipokine associated with obesity and metabolic syndrome in humans, representing a strong candidate gene potentially underlying the observed association. To evaluate whether the bovine chemerin gene is involved in feed intake, 16 markers within and around the gene were tested for association in the same resource population. Eleven were nominally significant for ADFI (P < 0.05) and two were significant after Bonferroni correction. Two and five SNP in this region were nominally significant for the related traits of average daily gain (ADG) and residual feed intake (RFI), respectively. All markers were evaluated for effects on meat quality and carcass phenotypes. Many of the markers associated with ADFI were associated with hot carcass weight (HCW), adjusted fat thickness (AFT), and marbling (P < 0.05). Marker alleles that were associated with lower ADFI were also associated with lower HCW, AFT, and marbling. Markers associated with ADFI were genotyped in a validation population of steers representing 14 breeds to determine predictive merit across populations. No consistent relationships for ADFI were detected. To determine whether cattle feed intake or growth phenotypes might be related to chemerin transcript abundance, the expression of chemerin was evaluated in adipose of 114 heifers that were siblings of the steers in the discovery population. Relative chemerin transcript abundance was not correlated with ADFI, ADG, or RFI, but associations with body condition score and yearling weight were observed. We conclude that variation in the chemerin gene may underlie observed association in the resource population, but that additional research is required to determine if this variation is widespread among breeds and to develop robust markers with predictive merit across breeds.

Dataset Information

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

Publications

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

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