@article {Maria Carolina126789, author = {Borges Maria Carolina and Barros Alu{\'\i}sio JD and Ferreira Diana L Santos and Casas Juan Pablo and Horta Bernardo Lessa and Kivimaki Mika and Kumari Meena and Usha Menon and Gaunt Tom R and Ben-Shlomo Yoav and Freitas Deise F and Oliveira Isabel O and Gentry-Maharaj Aleksandra and Fourkala Evangelia and Lawlor Debbie A and Hingorani Aroon D}, title = {Metabolic profiling of adiponectin levels in adults: Mendelian randomization analysis}, elocation-id = {126789}, year = {2017}, doi = {10.1101/126789}, publisher = {Cold Spring Harbor Laboratory}, abstract = {Background Adiponectin, a circulating adipocyte-derived protein has insulin-sensitizing, anti-inflammatory, anti-atherogenic, and cardiomyocyte-protective properties in animal models. However, the systemic effects of adiponectin in humans are unknown.Objectives Our aims were to define the metabolic profile associated with higher blood adiponectin concentration and investigate whether variation in adiponectin concentration affects the systemic metabolic profile.Methods We applied multivariable regression in up to 5,906 adults and Mendelian randomization (using cis-acting genetic variants in the vicinity of the adiponectin gene as instrumental variables) for analysing the causal effect of adiponectin in the metabolic profile of up to 38,058 adults. Participants were largely European from six longitudinal studies and one genome-wide association consortium.Results In the multivariable regression analyses, higher circulating adiponectin was associated with higher HDL lipids and lower VLDL lipids, glucose levels, branched-chain amino acids, and inflammatory markers. However, these findings were not supported by Mendelian randomization analyses for most metabolites. Findings were consistent between sexes and after excluding high risk groups (defined by age and occurrence of previous cardiovascular event) and one study with admixed population.Conclusion Our findings indicate that blood adiponectin concentration is more likely to be an epiphenomenon in the context of metabolic disease than a key determinant.}, URL = {https://www.biorxiv.org/content/early/2017/04/13/126789}, eprint = {https://www.biorxiv.org/content/early/2017/04/13/126789.full.pdf}, journal = {bioRxiv} }