Open AccessNine Loci for Ocular Axial Length Identified through Genome-wide Association Studies, Including Shared Loci with Refractive Error
Author(s) -
ChingYu Cheng,
Maria Schäche,
M. Kamran Ikram,
Terri L. Young,
Jeremy A. Guggenheim,
Véronique Vitart,
Stuart MacGregor,
Virginie J. M. Verhoeven,
Veluchamy A. Barathi,
Jiemin Liao,
Pirro G. Hysi,
Joan E. BaileyWilson,
Beaté St Pourcain,
John P. Kemp,
George McMahon,
Nicholas J. Timpson,
David M. Evans,
Grant W. Montgomery,
Aniket Mishra,
Ya Xing Wang,
Jie Jin Wang,
Elena Rochtchina,
Ozren Polašek,
Alan F. Wright,
Najaf Amin,
JinMoo Lee,
James F. Wilson,
Craig E. Pennell,
Cornelia M. van Duijn,
Paulus T.V.M. de Jong,
Johannes R. Vingerling,
Xin Zhou,
Peng Chen,
Ruoying Li,
Wan-Ting Tay,
Yingfeng Zheng,
Merwyn Chew,
Kathryn P. Burdon,
Jamie E. Craig,
Sudha K. Iyengar,
Robert P. Igo,
Jonathan H. Lass,
Emily Y. Chew,
Toomas Haller,
Evelin Mihailov,
Andres Metspalu,
Juho Wedenoja,
Claire L. Simpson,
Robert Wojciechowski,
René Höhn,
Alireza Mirshahi,
Tanja Zeller,
Norbert Pfeiffer,
Karl J. Lackner,
Thomas Bettecken,
Thomas Meitinger,
Konrad Oexle,
Mario Pirastu,
Laura Portas,
Abhishek Nag,
Katie Williams,
Ekaterina YonovaDoing,
Ronald Klein,
Barbara E.K. Klein,
S. Mohsen Hosseini,
Andrew D. Paterson,
Kari-Matti Mäkelä,
Terho Lehtimäki,
Mika Kähönen,
Olli T. Raitakari,
Nagahisa Yoshimura,
Fumihiko Matsuda,
Li Jia Chen,
Chi Pui Pang,
Shea Ping Yip,
Maurice Yap,
Akira Meguro,
Nobuhisa Mizuki,
Hidetoshi Inoko,
Paul J. Foster,
Wei Zhao,
Eranga N. Vithana,
E Shyong Tai,
Qiao Fan,
Liang Xu,
Harry Campbell,
Brian W. Fleck,
Igor Rudan,
Tin Aung,
Albert Hofman,
André G. Uitterlinden,
Goran Benčić,
Chiea Chuen Khor,
Hannah Forward,
Olavi Pärssinen,
Paul Mitchell,
Fernando Rivadeneira,
Alex W. Hewitt,
Cathy Williams,
Ben A. Oostra,
YikYing Teo,
Christopher J. Hammond,
Dwight Stambolian,
David A. Mackey,
Caroline C. W. Klaver,
Tien Yin Wong,
SeangMei Saw,
Paul N. Baird,
William J. Reinhart,
Michael W. Belin,
Robert L. Schultze,
Todd Morason,
Alan Sugar,
Shahzad I. Mian,
H. Kaz Soong,
Kathryn Colby,
Ula V. Jurkunas,
Richard W. Yee,
Mark Vital,
Eduardo García Alfonso,
Carol L. Karp,
Yunhee Lee,
Sonia H. Yoo,
K.M. Hammersmith,
Elisabeth J. Cohen,
Peter R. Laibson,
Christopher J. Rapuano,
Brandon D. Ayres,
Christopher R. Croasdale,
James W. Caudill,
Sanjay Patel,
Keith H. Baratz,
William M. Bourne,
Leo J. Maguire,
Joel Sugar,
Elmer Y. Tu,
Ali R. Djalilian,
Vinod V. Mootha,
James P. McCulley,
Wayne Bowman,
H. Dwight Cavanaugh,
Steven M. Verity,
David D. Verdier,
A. Renucci,
Matt Oliva,
Walter M. Rotkis,
David R. Hardten,
Ahmad Fahmy,
Marlene Brown,
Sherman W. Reeves,
Elizabeth A. Davis,
Richard L. Lindstrom,
Scott Hauswirth,
Stephen R. Hamilton,
W. Barry Lee,
Francis W. Price,
Marianne O. Price,
Kathleen Kelly,
Faye Peters,
Michael F. Shaughnessy,
Thomas L. Steinemann,
B.J. Dupps,
David M. Meisler,
Mark D. Mifflin,
Randal S. Olson,
Anthony J. Aldave,
Gary N. Holland,
Bartly J. Mondino,
George O. D. Rosenwasser,
Mark Gorovoy,
Steven P. Dunn,
David G. Heidemann,
Mark A. Terry,
Neda Shamie,
Steven I. Rosenfeld,
Brandon Suedekum,
David G. Hwang,
Donald U. Stone,
James Chodosh,
Paul Galentine,
David S. Bardenstein,
Katrina A.B. Goddard,
Hemin Chin,
Mark J. Mannis,
Rohit Varma,
Ingrid B. Borecki
Publication year - 2013
Publication title -
the american journal of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.661
H-Index - 302
eISSN - 1537-6605
pISSN - 0002-9297
DOI - 10.1016/j.ajhg.2013.06.016
Subject(s) - biology , locus (genetics) , genetics , genome wide association study , genetic association , refractive error , genome , gene , refraction , genotype , single nucleotide polymorphism , eye disease , optics , physics
Refractive errors are common eye disorders of public health importance worldwide. Ocular axial length (AL) is the major determinant of refraction and thus of myopia and hyperopia. We conducted a meta-analysis of genome-wide association studies for AL, combining 12,531 Europeans and 8,216 Asians. We identified eight genome-wide significant loci for AL (RSPO1, C3orf26, LAMA2, GJD2, ZNRF3, CD55, MIP, and ALPPL2) and confirmed one previously reported AL locus (ZC3H11B). Of the nine loci, five (LAMA2, GJD2, CD55, ALPPL2, and ZC3H11B) were associated with refraction in 18 independent cohorts (n = 23,591). Differential gene expression was observed for these loci in minus-lens-induced myopia mouse experiments and human ocular tissues. Two of the AL genes, RSPO1 and ZNRF3, are involved in Wnt signaling, a pathway playing a major role in the regulation of eyeball size. This study provides evidence of shared genes between AL and refraction, but importantly also suggests that these traits may have unique pathways.
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