[저자] Yoonjung Yoonie Joo, Ky’Era Actkins, Jennifer A Pacheco, Anna O Basile, Robert Carroll, David R Crosslin, Felix Day, Joshua C Denny, Digna R Velez Edwards, Hakon Hakonarson, John B Harley, Scott J Hebbring, Kevin Ho, Gail P Jarvik, Michelle Jones, Tugce Karaderi, Frank D Mentch, Cindy Meun, Bahram Namjou, Sarah Pendergrass, Marylyn D Ritchie, Ian B Stanaway, Margrit Urbanek, Theresa L Walunas, Maureen Smith, Rex L Chisholm, Abel N Kho, Lea Davis, M Geoffrey Hayes,
International PCOS Consortium
DayFelixKaraderiTugceJonesMichelle RMeunCindyHeChunyanDrongAlexKraftPeterLinNanHuangHongyanBroerLindaMagiReedikSaxenaRichaLaisk-PodarTriinUrbanekMargritHayesM GeoffreyThorleifssonGudmarFernandez-TajesJuanMahajanAnubhaMullinBenjamin HStuckeyBronwyn G ASpectorTimothy DWilsonScott GGoodarziMark ODavisLeaObermeyer-PietschBarbaraUitterlindenAndré GAnttilaVerneriNealeBenjamin MJarvelinMarjo-RiittaFauserBartKowalskaIrinaVisserJenny AAndersonMarianneOngKenStener-VictorinElisabetEhrmannDavidLegroRichard SSalumetsAndresMcCarthyMark IMorin-PapunenLaureThorsteinsdottirUnnurStefanssonKariStyrkarsdottirUnnurPerryJohnDunaifAndreaLavenJoopFranksSteveLindgrenCecilia MWeltCorrine K
, Felix Day, Tugce Karaderi, Michelle R Jones, Cindy Meun, Chunyan He, Alex Drong, Peter Kraft, Nan Lin, Hongyan Huang, Linda Broer, Reedik Magi, Richa Saxena, Triin Laisk-Podar, Margrit Urbanek, M Geoffrey Hayes, Gudmar Thorleifsson, Juan Fernandez-Tajes, Anubha Mahajan, Benjamin H Mullin, Bronwyn G A Stuckey, Timothy D Spector, Scott G Wilson, Mark O Goodarzi, Lea Davis, Barbara Obermeyer-Pietsch, André G Uitterlinden, Verneri Anttila, Benjamin M Neale, Marjo-Riitta Jarvelin, Bart Fauser, Irina Kowalska, Jenny A Visser, Marianne Anderson, Ken Ong, Elisabet Stener-Victorin, David Ehrmann, Richard S Legro, Andres Salumets, Mark I McCarthy, Laure Morin-Papunen, Unnur Thorsteinsdottir, Kari Stefansson, Unnur Styrkarsdottir, John Perry, Andrea Dunaif, Joop Laven, Steve Franks, Cecilia M Lindgren, Corrine K Welt
[Category] 대상포진,
[Article Type] Clinical Research Article
[Source] PMC
Abstract Context As many as 75% of patients with polycystic ovary syndrome (PCOS) are estimated to be unidentified in clinical practice. Objective Utilizing polygenic risk prediction, we aim to identify the phenome-wide comorbidity patterns characteristic of PCOS to improve accurate diagnosis and preventive treatment. Design, Patients, and Methods Leveraging the electronic health records (EHRs) of 124 852 individuals, we developed a PCOS risk prediction algorithm by combining polygenic risk scores (PRS) with PCOS component phenotypes into a polygenic and phenotypic risk score (PPRS). We evaluated its predictive capability across different ancestries and perform a PRS-based phenome-wide association study (PheWAS) to assess the phenomic expression of the heightened risk of PCOS. Results The integrated polygenic prediction improved the average performance (pseudo-R^{2}) for PCOS detection by 0.228 (61.5-fold), 0.224 (58.8-fold), 0.211 (57.0-fold) over the null model across European, African, and multi-ancestry participants respectively. The subsequent PRS-powered PheWAS identified a high level of shared biology between PCOS and a range of metabolic and endocrine outcomes, especially with obesity and diabetes: “morbid obesity”, “type 2 diabetes”, “hypercholesterolemia”, “disorders of lipid metabolism”, “hypertension”, and “sleep apnea” reaching phenome-wide significance. Conclusions Our study has expanded the methodological utility of PRS in patient stratification and risk prediction, especially in a multifactorial condition like PCOS, across different genetic origins. By utilizing the individual genome–phenome data available from the EHR, our approach also demonstrates that polygenic prediction by PRS can provide valuable opportunities to discover the pleiotropic phenomic network associated with PCOS pathogenesis.
All Keywords
【저자키워드】 Polycystic ovary syndrome, polygenic risk score, Phenome-wide association study, genomic prediction,