Imperial College London
Alternate

ProfessorPaulElliott

Faculty of Medicine, School of Public Health

Chair in Epidemiology and Public Health Medicine
 
 
 
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Contact

 

+44 (0)20 7594 3328p.elliott Website

 
 
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Assistant

 

Miss Jennifer Wells +44 (0)20 7594 3328

 
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Location

 

154Norfolk PlaceSt Mary's Campus

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Summary

 

Publications

Citation

BibTex format

@article{Turcot:2017:10.1038/s41588-017-0011-x,
author = {Turcot, V and Chambers, J and Elliott, P and Evangelou, E and Kooner, J and Zhang, W and Loos, R},
doi = {10.1038/s41588-017-0011-x},
journal = {Nature Genetics},
pages = {26--41},
title = {Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesity.},
url = {http://dx.doi.org/10.1038/s41588-017-0011-x},
volume = {50},
year = {2017}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Genome-wide association studies (GWAS) have identified >250 loci for body mass index (BMI), implicating pathways related to neuronal biology. Most GWAS loci represent clusters of common, noncoding variants from which pinpointing causal genes remains challenging. Here we combined data from 718,734 individuals to discover rare and low-frequency (minor allele frequency (MAF) < 5%) coding variants associated with BMI. We identified 14 coding variants in 13 genes, of which 8 variants were in genes (ZBTB7B, ACHE, RAPGEF3, RAB21, ZFHX3, ENTPD6, ZFR2 and ZNF169) newly implicated in human obesity, 2 variants were in genes (MC4R and KSR2) previously observed to be mutated in extreme obesity and 2 variants were in GIPR. The effect sizes of rare variants are ~10 times larger than those of common variants, with the largest effect observed in carriers of an MC4R mutation introducing a stop codon (p.Tyr35Ter, MAF = 0.01%), who weighed ~7 kg more than non-carriers. Pathway analyses based on the variants associated with BMI confirm enrichment of neuronal genes and provide new evidence for adipocyte and energy expenditure biology, widening the potential of genetically supported therapeutic targets in obesity.
AU  - Turcot,V
AU  - Chambers,J
AU  - Elliott,P
AU  - Evangelou,E
AU  - Kooner,J
AU  - Zhang,W
AU  - Loos,R
DO  - 10.1038/s41588-017-0011-x
EP  - 41
PY  - 2017///
SN  - 1061-4036
SP  - 26
TI  - Protein-altering variants associated with body mass index implicate pathways that control energy intake and expenditure underpinning obesity.
T2  - Nature Genetics
UR  - http://dx.doi.org/10.1038/s41588-017-0011-x
UR  - http://hdl.handle.net/10044/1/55169
VL  - 50
ER  -
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