Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator

Jérôme Carayol (), Christian Chabert, Alessandro Di Cara, Claudia Armenise, Gregory Lefebvre, Dominique Langin, Nathalie Viguerie, Sylviane Metairon, Wim H. M. Saris, Arne Astrup, Patrick Descombes, Armand Valsesia and Jörg Hager
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Jérôme Carayol: EPFL Innovation Park
Christian Chabert: EPFL Innovation Park
Alessandro Di Cara: Quartz Bio
Claudia Armenise: Quartz Bio
Gregory Lefebvre: EPFL Innovation Park
Dominique Langin: University of Toulouse
Nathalie Viguerie: University of Toulouse
Sylviane Metairon: EPFL Innovation Park
Wim H. M. Saris: Maastricht University Medical Centre
Arne Astrup: University of Copenhagen
Patrick Descombes: EPFL Innovation Park
Armand Valsesia: EPFL Innovation Park
Jörg Hager: EPFL Innovation Park

Nature Communications, 2017, vol. 8, issue 1, 1-14

Abstract: Abstract Thousands of genetic variants have been associated with complex traits through genome-wide association studies. However, the functional variants or mechanistic consequences remain elusive. Intermediate traits such as gene expression or protein levels are good proxies of the metabolic state of an organism. Proteome analysis especially can provide new insights into the molecular mechanisms of complex traits like obesity. The role of genetic variation in determining protein level variation has not been assessed in obesity. To address this, we design a large-scale protein quantitative trait locus (pQTL) analysis based on a set of 1129 proteins from 494 obese subjects before and after a weight loss intervention. This reveals 55 BMI-associated cis-pQTLs and trans-pQTLs at baseline and 3 trans-pQTLs after the intervention. We provide evidence for distinct genetic mechanisms regulating BMI-associated proteins before and after weight loss. Finally, by functional analysis, we identify and validate FAM46A as a trans regulator for leptin.

Date: 2017
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DOI: 10.1038/s41467-017-02182-z

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