Genetic architecture of human thinness compared to severe obesity

Publication type

Journal Article

Published in

PLoS Genetics

Authors

Fernando Riveros-McKay, Vanisha Mistry, Rebecca Bounds, Audrey Hendricks, Julia M. Keogh, Hannah Thomas, Elana Henning, Laura J. Corbin, Stephen O’Rahilly, Eleftheria Zeggini, Eleanor Wheeler, Inês Barroso and I. Sadaf FarooqiI

Publication date

Summary

Author summary: Obesity-associated disorders are amongst the leading causes of morbidity and mortality worldwide. Most genome-wide association studies (GWAS) have focused on body mass index (BMI = weight in Kg divided by height squared (m2)) and obesity, but to date no genetic association study testing thin and healthy individuals has been performed. In this study, we recruited a first of its kind cohort of 1,471 clinically ascertained thin and healthy individuals and contrasted the genetic architecture of the trait with that of severe early onset obesity. We show that thinness, like obesity, is a heritable trait with a polygenic component. In a GWAS of persistent healthy thinness vs. severe obesity with a total sample size of 2,927, we are able to find evidence of association in loci that have only been recently discovered using large cohorts with >40,000 individuals. We also find a novel BMI-associated locus at PKHD1 in UK Biobank highlighted by our association study. This work illustrates the value and increased power brought upon by using clinically ascertained extremes to study complex traits and provides a valuable resource on which to study resistance to obesity in an increasingly obesogenic environment.

Volume

15

DOI

https://doi.org/10.1371/journal.pgen.1007603

ISSN

16

Subjects

Health, Biology and Genetics

Notes

© 2019 Riveros-McKay et al.; This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.