Rare Variant Analysis of Human and Rodent Obesity Genes in Individuals with Severe Childhood Obesity.

Audrey E Hendricks, Elena G Bochukova, Gaëlle Marenne, Julia Keogh, Neli Atanassova, Rebecca Bounds, Eleanor Wheeler, Vanisha Mistry, Elana Henning, Antje Körner, Dawn Muddyman, Shane McCarthy, Anke Hinney, Johannes Hebebrand, Robert A Scott, Claudia Langenberg, Nicholas Wareham, Praveen Surendran, Joanna Howson, Adam Butterworth, John Danesh, Børge G Nordestgaard, Sune F Nielsen, Shoaib Afzal, Sofia Papadia … & UK10K Consortium
Obesity is a genetically heterogeneous disorder. Using targeted and whole-exome sequencing, we studied 32 human and 87 rodent obesity genes in 2,548 severely obese children and 1,117 controls. We identified 52 variants contributing to obesity in 2% of cases including multiple novel variants in GNAS, which were sometimes found with accelerated growth rather than short stature as described previously. Nominally significant associations were found for rare functional variants in BBS1, BBS9, GNAS, MKKS, CLOCK and...
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