BibTex format
@article{Marouli:2017:10.1038/nature21039,
author = {Marouli, E and Graff, M and Medina-Gomez, C and Lo, KS and Wood, AR and Kjaer, TR and Fine, RS and Lu, Y and Elliott, P and Chambers, JC and Evangelou, E and Kooner, JS and Oxvig, C and Kutalik, Z and Rivadeneira, F and Loos, RJF and Frayling, TM and Hirschorn, JS and Deloukas, P and Lettre, G},
doi = {10.1038/nature21039},
journal = {Nature},
pages = {186--190},
title = {Rare and low-frequency coding variants alter human adult height},
url = {http://dx.doi.org/10.1038/nature21039},
volume = {542},
year = {2017}
}
RIS format (EndNote, RefMan)
TY - JOUR
AB - Heightis a highly heritable, classic polygenic traitwith~700common associated variants identified so far through genome-wide association studies. Here,we report 83 height-associated codingvariants with lowerminor allele frequencies(range of0.1-4.8%)and effects ofup to 2 16cm/allele(e.g.in IHH, STC2, ARand CRISPLD2), >10timesthe average effect of common variants.In functional follow-upstudies,rare height-increasing allelesof STC2(+1-2 cm/allele) compromisedproteolytic inhibition of PAPP-A and increased cleavage of IGFBP-4in vitro, resulting in higher bioavailability of insulin-like growth factors.These 83height-associated variants overlapgenes mutated in monogenic growth disordersand highlight new biological candidates (e.g. ADAMTS3, IL11RA, NOX4) and pathways (e.g. proteoglycan/glycosaminoglycan synthesis)involved in growth.Our results demonstratethatsufficiently large sample sizescan uncoverrare and low-frequency variants of moderate to large effect associated with polygenic human phenotypes,andthat these variantsimplicate relevant genes and pathways.
AU - Marouli,E
AU - Graff,M
AU - Medina-Gomez,C
AU - Lo,KS
AU - Wood,AR
AU - Kjaer,TR
AU - Fine,RS
AU - Lu,Y
AU - Elliott,P
AU - Chambers,JC
AU - Evangelou,E
AU - Kooner,JS
AU - Oxvig,C
AU - Kutalik,Z
AU - Rivadeneira,F
AU - Loos,RJF
AU - Frayling,TM
AU - Hirschorn,JS
AU - Deloukas,P
AU - Lettre,G
DO - 10.1038/nature21039
EP - 190
PY - 2017///
SN - 0028-0836
SP - 186
TI - Rare and low-frequency coding variants alter human adult height
T2 - Nature
UR - http://dx.doi.org/10.1038/nature21039
UR - http://hdl.handle.net/10044/1/43708
VL - 542
ER -
