Publication type
Journal Article
Authors
- Magdalena Zoledziewska
- Carlo Sidore
- Charleston W. K. Chiang
- Serena Sanna
- Antonella Mulas
- Maristella Steri
- Fabio Busonero
- Joseph H. Marcus
- Andrea Maschio
- Diego Ortega Del Vecchyo
- Matteo Floris
- Antonella Meloni
- Alessandro Delitala
- Maria Pina Concas
- Federico Murgia
- Ginevra Biino
- Simona Vaccargiu
- Ramaiah Nagaraja
- Kirk E. Lohmueller
- Nicholas J. Timpson
- Nicole Soranzo
- Ioanna Tachmazidou
- George Dedoussis
- Eleftheria Zeggini
- Sergio Uzzau
- Chris Jones
- Robert Lyons
- Andrea Angius
- Goncalo R. Abecasis
- John Novembre
- David Schlessinger
- Francesco Cucca
Publication date
June 1, 2015
Summary:
We report sequencing-based whole-genome association analyses to evaluate the impact of rare and founder variants on stature in 6,307 individuals on the island of Sardinia. We identify two variants with large effects. One variant, which introduces a stop codon in the GHR gene, is relatively frequent in Sardinia (0.87% versus <0.01% elsewhere) and in the homozygous state causes Laron syndrome involving short stature. We find that this variant reduces height in heterozygotes by an average of 4.2 cm (−0.64 s.d.). The other variant, in the imprinted KCNQ1 gene (minor allele frequency (MAF) = 7.7% in Sardinia versus <1% elsewhere) reduces height by an average of 1.83 cm (−0.31 s.d.) when maternally inherited. Additionally, polygenic scores indicate that known height-decreasing alleles are at systematically higher frequencies in Sardinians than would be expected by genetic drift. The findings are consistent with selection for shorter stature in Sardinia and a suggestive human example of the proposed 'island effect' reducing the size of large mammals.
Published in
Nature Genetics
Volume and page numbers
Volume: 47 , p.1 -1
DOI
http://dx.doi.org/10.1038/ng.3403
ISSN
10614036
Subjects
#523748