Skip to content

Journal Article

Genetic architecture of human thinness compared to severe obesity


Publication date

24 Jan 2019


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.

Published in

PLoS Genetics







Health, Biology, and Genetics


© 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.


Research home

Research home


Latest findings, new research

Publications search

Search all research by subject and author


Researchers discuss their findings and what they mean for society


Background and context, methods and data, aims and outputs


Conferences, seminars and workshops

Survey methodology

Specialist research, practice and study

Taking the long view

ISER's annual report


Key research themes and areas of interest