Publications

BibTex format

@article{Day:2018:10.1371/journal.pgen.1007813,
author = {Day, F and Karaderi, T and Jones, MR and Meun, C and He, C and Drong, A and Kraft, P and Lin, N and Huang, H and Broer, L and Magi, R and Saxena, R and Laisk, T and Urbanek, M and Hayes, MG and Thorleifsson, G and Fernandez-Tajes, J and Mahajan, A and Mullin, BH and Stuckey, BGA and Spector, TD and Wilson, SG and Goodarzi, MO and Davis, L and Obermayer-Pietsch, B and Uitterlinden, AG and Anttila, V and Neale, BM and Jarvelin, M-R and Fauser, B and Kowalska, I and Visser, JA and Andersen, M and Ong, K and Stener-Victorin, E and Ehrmann, D and Legro, RS and Salumets, A and McCarthy, MI and Morin-Papunen, L and Thorsteinsdottir, U and Stefansson, K and Styrkarsdottir, U and Perry, JRB and Dunaif, A and Laven, J and Franks, S and Lindgren, CM and Welt, CK},
doi = {10.1371/journal.pgen.1007813},
journal = {PLoS Genetics},
pages = {1--20},
title = {Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria},
url = {http://dx.doi.org/10.1371/journal.pgen.1007813},
volume = {14},
year = {2018}
}

Download

RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Polycystic ovary syndrome (PCOS) is a disorder characterized by hyperandrogenism, ovulatory dysfunction and polycystic ovarian morphology. Affected women frequently have metabolic disturbances including insulin resistance and dysregulation of glucose homeostasis. PCOS is diagnosed with two different sets of diagnostic criteria, resulting in a phenotypic spectrum of PCOS cases. The genetic similarities between cases diagnosed based on the two criteria have been largely unknown. Previous studies in Chinese and European subjects have identified 16 loci associated with risk of PCOS. We report a fixed-effect, inverse-weighted-variance meta-analysis from 10,074 PCOS cases and 103,164 controls of European ancestry and characterisation of PCOS related traits. We identified 3 novel loci (near PLGRKT, ZBTB16 and MAPRE1), and provide replication of 11 previously reported loci. Only one locus differed significantly in its association by diagnostic criteria; otherwise the genetic architecture was similar between PCOS diagnosed by self-report and PCOS diagnosed by NIH or non-NIH Rotterdam criteria across common variants at 13 loci. Identified variants were associated with hyperandrogenism, gonadotropin regulation and testosterone levels in affected women. Linkage disequilibrium score regression analysis revealed genetic correlations with obesity, fasting insulin, type 2 diabetes, lipid levels and coronary artery disease, indicating shared genetic architecture between metabolic traits and PCOS. Mendelian randomization analyses suggested variants associated with body mass index, fasting insulin, menopause timing, depression and male-pattern balding play a causal role in PCOS. The data thus demonstrate 3 novel loci associated with PCOS and similar genetic architecture for all diagnostic criteria. The data also provide the first genetic evidence for a male phenotype for PCOS and a causal link to depression, a previously hypothesized comorbid disease. Thus, the genetics provide a comp
AU  - Day,F
AU  - Karaderi,T
AU  - Jones,MR
AU  - Meun,C
AU  - He,C
AU  - Drong,A
AU  - Kraft,P
AU  - Lin,N
AU  - Huang,H
AU  - Broer,L
AU  - Magi,R
AU  - Saxena,R
AU  - Laisk,T
AU  - Urbanek,M
AU  - Hayes,MG
AU  - Thorleifsson,G
AU  - Fernandez-Tajes,J
AU  - Mahajan,A
AU  - Mullin,BH
AU  - Stuckey,BGA
AU  - Spector,TD
AU  - Wilson,SG
AU  - Goodarzi,MO
AU  - Davis,L
AU  - Obermayer-Pietsch,B
AU  - Uitterlinden,AG
AU  - Anttila,V
AU  - Neale,BM
AU  - Jarvelin,M-R
AU  - Fauser,B
AU  - Kowalska,I
AU  - Visser,JA
AU  - Andersen,M
AU  - Ong,K
AU  - Stener-Victorin,E
AU  - Ehrmann,D
AU  - Legro,RS
AU  - Salumets,A
AU  - McCarthy,MI
AU  - Morin-Papunen,L
AU  - Thorsteinsdottir,U
AU  - Stefansson,K
AU  - Styrkarsdottir,U
AU  - Perry,JRB
AU  - Dunaif,A
AU  - Laven,J
AU  - Franks,S
AU  - Lindgren,CM
AU  - Welt,CK
DO  - 10.1371/journal.pgen.1007813
EP  - 20
PY  - 2018///
SN  - 1553-7390
SP  - 1
TI  - Large-scale genome-wide meta-analysis of polycystic ovary syndrome suggests shared genetic architecture for different diagnosis criteria
T2  - PLoS Genetics
UR  - http://dx.doi.org/10.1371/journal.pgen.1007813
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000455099000014&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1007813
UR  - http://hdl.handle.net/10044/1/66285
VL  - 14
ER  -

Download

Emeritus ProfessorStephenFranks

Contact

Assistant

Location

Summary

Citation

BibTex format

RIS format (EndNote, RefMan)