Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator
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Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator. / Carayol, Jérôme; Chabert, Christian; Di Cara, Alessandro; Armenise, Claudia; Lefebvre, Gregory; Langin, Dominique; Viguerie, Nathalie; Metairon, Sylviane; Saris, Wim H M; Astrup, Arne; Descombes, Patrick; Valsesia, Armand; Hager, Jörg.
In: Nature Communications, Vol. 8, 2084, 2017.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Protein quantitative trait locus study in obesity during weight-loss identifies a leptin regulator
AU - Carayol, Jérôme
AU - Chabert, Christian
AU - Di Cara, Alessandro
AU - Armenise, Claudia
AU - Lefebvre, Gregory
AU - Langin, Dominique
AU - Viguerie, Nathalie
AU - Metairon, Sylviane
AU - Saris, Wim H M
AU - Astrup, Arne
AU - Descombes, Patrick
AU - Valsesia, Armand
AU - Hager, Jörg
N1 - CURIS 2017 NEXS 348
PY - 2017
Y1 - 2017
N2 - Thousands of genetic variants have been associated with complex traits through genomewide 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.
AB - Thousands of genetic variants have been associated with complex traits through genomewide 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.
KW - Faculty of Science
KW - Proteome analysis
KW - Complex traits
KW - Obesity
KW - Protein quantitative trait locus (pQTL)
KW - Weight loss
KW - BMI-associated proteins
KW - FAM46A
KW - Trans regulator for leptin
U2 - 10.1038/s41467-017-02182-z
DO - 10.1038/s41467-017-02182-z
M3 - Journal article
C2 - 29234017
VL - 8
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 2084
ER -
ID: 186710314