TY - JOUR
T1 - Rare variant analyses across multiethnic cohorts identify novel genes for refractive error
AU - Musolf, Anthony M.
AU - Haarman, Annechien E.G.
AU - Luben, Robert N.
AU - Ong, Jue-Sheng
AU - Patasova, Karina
AU - Trapero, Rolando Hernandez
AU - Marsh, Joseph
AU - Jain, Ishika
AU - Jain, Riya
AU - Wang, Paul Zhiping
AU - Lewis, Deyana D.
AU - Tedja, Milly S.
AU - Iglesias, Adriana I.
AU - Li, Hengtong
AU - Cowan, Cameron S.
AU - The CREAM Consortium
AU - Baird, Paul Nigel
AU - Veluchamy, Amutha Barathi
AU - Burdon, Kathryn P.
AU - Campbell, Harry
AU - Chen, Li Jia
AU - Chew, Emily Y.
AU - Craig, Jamie E.
AU - Cumberland, Phillippa M.
AU - Deangelis, Margaret M.
AU - Delcourt, Cécile
AU - Ding, Xiaohu
AU - Evans, David M.
AU - Fan, Qiao
AU - Fossarello, Maurizio
AU - Foster, Paul J.
AU - Gharahkhani, Puya
AU - Guggenheim, Jeremy A.
AU - Guo, Xiaobo
AU - Han, Xikun
AU - He, Mingguang
AU - Hewitt, Alex W.
AU - Hoang, Quan V.
AU - Iyengar, Sudha K.
AU - Jonas, Jost B.
AU - Kähönen, Mika
AU - Kaprio, Jaakko
AU - Klein, Barbara E.
AU - Lass, Jonathan H.
AU - Lee, Kris
AU - Lehtimäki, Terho
AU - Li, Qing
AU - Li, Shi-Ming
AU - Lyytikäinen, Leo-Pekka
AU - MacGregor, Stuart
AU - Martin, Nicholas G.
AU - Meguro, Akira
AU - Middlebrooks, Candace
AU - Miyake, Masahiro
AU - Mizuki, Nobuhisa
AU - Nickels, Stefan
AU - Oexle, Konrad
AU - Pang, Chi Pui
AU - Paterson, Andrew D.
AU - Pennell, Craig
AU - Pfeiffer, Norbert
AU - Polasek, Ozren
AU - Rahi, Jugnoo S.
AU - Raitakari, Olli
AU - Rudan, Igor
AU - Sahebjada, Srujana
AU - Simpson, Claire L.
AU - Tai, E-Shyong
AU - Tideman, J. Willem L.
AU - Tsujikawa, Akitaka
AU - Wang, Ningli
AU - Bin Wei, Wen
AU - Williams, Cathy
AU - Williams, Katie M.
AU - Wilson, James F.
AU - Wojciechowski, Robert
AU - Wang, Ya Xing
AU - Yamashiro, Kenji
AU - Yam, Jason C.S.
AU - Yap, Maurice K.H.
AU - Yazar, Seyhan
AU - Yip, Shea Ping
AU - Young, Terri L.
AU - Zhou, Xiangtian
AU - Biino, Ginevra
AU - Klein, Alison P.
AU - Duggal, Priya
AU - Mackey, David A.
AU - Hayward, Caroline
AU - Haller, Toomas
AU - Metspalu, Andres
AU - Wedenoja, Juho
AU - Pärssinen, Olavi
AU - Cheng, Ching-Yu
AU - Saw, Seang Mei
AU - Stambolian, Dwight
AU - Hysi, Pirro G.
AU - Khawaja, Anthony P.
AU - Vitart, Veronique
AU - Hammond, Christopher J.
AU - van Duijn, Cornelia M.
AU - Verhoeven, Virginie J.M.
AU - Klaver, Caroline C.W.
AU - Bailey-Wilson, Joan E.
PY - 2023/12
Y1 - 2023/12
N2 - Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.
AB - Refractive error, measured here as mean spherical equivalent (SER), is a complex eye condition caused by both genetic and environmental factors. Individuals with strong positive or negative values of SER require spectacles or other approaches for vision correction. Common genetic risk factors have been identified by genome-wide association studies (GWAS), but a great part of the refractive error heritability is still missing. Some of this heritability may be explained by rare variants (minor allele frequency [MAF] ≤ 0.01.). We performed multiple gene-based association tests of mean Spherical Equivalent with rare variants in exome array data from the Consortium for Refractive Error and Myopia (CREAM). The dataset consisted of over 27,000 total subjects from five cohorts of Indo-European and Eastern Asian ethnicity. We identified 129 unique genes associated with refractive error, many of which were replicated in multiple cohorts. Our best novel candidates included the retina expressed PDCD6IP, the circadian rhythm gene PER3, and P4HTM, which affects eye morphology. Future work will include functional studies and validation. Identification of genes contributing to refractive error and future understanding of their function may lead to better treatment and prevention of refractive errors, which themselves are important risk factors for various blinding conditions.
KW - Genetic predisposition to disease
KW - Genome-wide association studies
KW - Microarrays
KW - Quantitative trait
KW - Quantitative trait loci
UR - http://www.scopus.com/inward/record.url?scp=85145431063&partnerID=8YFLogxK
U2 - 10.1038/s42003-022-04323-7
DO - 10.1038/s42003-022-04323-7
M3 - Article
C2 - 36596879
AN - SCOPUS:85145431063
SN - 2399-3642
VL - 6
JO - Communications Biology
JF - Communications Biology
IS - 1
M1 - 6
ER -