Centre for Eye Research Australia (CERA) - Research Publications

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    A saturated map of common genetic variants associated with human height
    Yengo, L ; Vedantam, S ; Marouli, E ; Sidorenko, J ; Bartell, E ; Sakaue, S ; Graff, M ; Eliasen, AU ; Jiang, Y ; Raghavan, S ; Miao, J ; Arias, JD ; Graham, SE ; Mukamel, RE ; Spracklen, CN ; Yin, X ; Chen, S-H ; Ferreira, T ; Highland, HH ; Ji, Y ; Karaderi, T ; Lin, K ; Lull, K ; Malden, DE ; Medina-Gomez, C ; Machado, M ; Moore, A ; Rueger, S ; Sim, X ; Vrieze, S ; Ahluwalia, TS ; Akiyama, M ; Allison, MA ; Alvarez, M ; Andersen, MK ; Ani, A ; Appadurai, V ; Arbeeva, L ; Bhaskar, S ; Bielak, LF ; Bollepalli, S ; Bonnycastle, LL ; Bork-Jensen, J ; Bradfield, JP ; Bradford, Y ; Braund, PS ; Brody, JA ; Burgdorf, KS ; Cade, BE ; Cai, H ; Cai, Q ; Campbell, A ; Canadas-Garre, M ; Catamo, E ; Chai, J-F ; Chai, X ; Chang, L-C ; Chang, Y-C ; Chen, C-H ; Chesi, A ; Choi, SH ; Chung, R-H ; Cocca, M ; Concas, MP ; Couture, C ; Cuellar-Partida, G ; Danning, R ; Daw, EW ; Degenhard, F ; Delgado, GE ; Delitala, A ; Demirkan, A ; Deng, X ; Devineni, P ; Dietl, A ; Dimitriou, M ; Dimitrov, L ; Dorajoo, R ; Ekici, AB ; Engmann, JE ; Fairhurst-Hunter, Z ; Farmaki, A-E ; Faul, JD ; Fernandez-Lopez, J-C ; Forer, L ; Francescatto, M ; Freitag-Wolf, S ; Fuchsberger, C ; Galesloot, TE ; Gao, Y ; Gao, Z ; Geller, F ; Giannakopoulou, O ; Giulianini, F ; Gjesing, AP ; Goel, A ; Gordon, SD ; Gorski, M ; Grove, J ; Guo, X ; Gustafsson, S ; Haessler, J ; Hansen, TF ; Havulinna, AS ; Haworth, SJ ; He, J ; Heard-Costa, N ; Hebbar, P ; Hindy, G ; Ho, Y-LA ; Hofer, E ; Holliday, E ; Horn, K ; Hornsby, WE ; Hottenga, J-J ; Huang, H ; Huang, J ; Huerta-Chagoya, A ; Huffman, JE ; Hung, Y-J ; Huo, S ; Hwang, MY ; Iha, H ; Ikeda, DD ; Isono, M ; Jackson, AU ; Jager, S ; Jansen, IE ; Johansson, I ; Jonas, JB ; Jonsson, A ; Jorgensen, T ; Kalafati, I-P ; Kanai, M ; Kanoni, S ; Karhus, LL ; Kasturiratne, A ; Katsuya, T ; Kawaguchi, T ; Kember, RL ; Kentistou, KA ; Kim, H-N ; Kim, YJ ; Kleber, ME ; Knol, MJ ; Kurbasic, A ; Lauzon, M ; Le, P ; Lea, R ; Lee, J-Y ; Leonard, HL ; Li, SA ; Li, X ; Li, X ; Liang, J ; Lin, H ; Lin, S-Y ; Liu, J ; Liu, X ; Lo, KS ; Long, J ; Lores-Motta, L ; Luan, J ; Lyssenko, V ; Lyytikainen, L-P ; Mahajan, A ; Mamakou, V ; Mangino, M ; Manichaikul, A ; Marten, J ; Mattheisen, M ; Mavarani, L ; McDaid, AF ; Meidtner, K ; Melendez, TL ; Mercader, JM ; Milaneschi, Y ; Miller, JE ; Millwood, IY ; Mishra, PP ; Mitchell, RE ; Mollehave, LT ; Morgan, A ; Mucha, S ; Munz, M ; Nakatochi, M ; Nelson, CP ; Nethander, M ; Nho, CW ; Nielsen, AA ; Nolte, IM ; Nongmaithem, SS ; Noordam, R ; Ntalla, I ; Nutile, T ; Pandit, A ; Christofidou, P ; Parna, K ; Pauper, M ; Petersen, ERB ; Petersen, L ; Pitkanen, N ; Polasek, O ; Poveda, A ; Preuss, MH ; Pyarajan, S ; Raffield, LM ; Rakugi, H ; Ramirez, J ; Rasheed, A ; Raven, D ; Rayner, NW ; Riveros, C ; Rohde, R ; Ruggiero, D ; Ruotsalainen, SE ; Ryan, KA ; Sabater-Lleal, M ; Saxena, R ; Scholz, M ; Sendamarai, A ; Shen, B ; Shi, J ; Shin, JH ; Sidore, C ; Sitlani, CM ; Slieker, RKC ; Smit, RAJ ; Smith, A ; Smith, JA ; Smyth, LJ ; Southam, LE ; Steinthorsdottir, V ; Sun, L ; Takeuchi, F ; Tallapragada, D ; Taylor, KD ; Tayo, BO ; Tcheandjieu, C ; Terzikhan, N ; Tesolin, P ; Teumer, A ; Theusch, E ; Thompson, DJ ; Thorleifsson, G ; Timmers, PRHJ ; Trompet, S ; Turman, C ; Vaccargiu, S ; van der Laan, SW ; van der Most, PJ ; van Klinken, JB ; van Setten, J ; Verma, SS ; Verweij, N ; Veturi, Y ; Wang, CA ; Wang, C ; Wang, L ; Wang, Z ; Warren, HR ; Wei, WB ; Wickremasinghe, AR ; Wielscher, M ; Wiggins, KL ; Winsvold, BS ; Wong, A ; Wu, Y ; Wuttke, M ; Xia, R ; Xie, T ; Yamamoto, K ; Yang, J ; Yao, J ; Young, H ; Yousri, NA ; Yu, L ; Zeng, L ; Zhang, W ; Zhang, X ; Zhao, J-H ; Zhao, W ; Zhou, W ; Zimmermann, ME ; Zoledziewska, M ; Adair, LS ; Adams, HHH ; Aguilar-Salinas, CA ; Al-Mulla, F ; Arnett, DK ; Asselbergs, FW ; Asvold, BO ; Attia, J ; Banas, B ; Bandinelli, S ; Bennett, DA ; Bergler, T ; Bharadwaj, D ; Biino, G ; Bisgaard, H ; Boerwinkle, E ; Boger, CA ; Bonnelykke, K ; Boomsma, D ; Borglum, AD ; Borja, JB ; Bouchard, C ; Bowden, DW ; Brandslund, I ; Brumpton, B ; Buring, JE ; Caulfield, MJ ; Chambers, JC ; Chandak, GR ; Chanock, SJ ; Chaturvedi, N ; Chen, Y-DI ; Chen, Z ; Cheng, C-Y ; Christophersen, IE ; Ciullo, M ; Cole, JW ; Collins, FS ; Cooper, RS ; Cruz, M ; Cucca, F ; Cupples, LA ; Cutler, MJ ; Damrauer, SM ; Dantoft, TM ; de Borst, GJ ; de Groot, LCPGM ; De Jager, PL ; de Kleijn, DP ; de Silva, HJ ; Dedoussis, G ; den Hollander, A ; Du, S ; Easton, DF ; Elders, PJM ; Eliassen, AH ; Ellinor, PT ; Elmstahl, S ; Erdmann, J ; Evans, MK ; Fatkin, D ; Feenstra, B ; Feitosa, MF ; Ferrucci, L ; Ford, I ; Fornage, M ; Franke, A ; Franks, PW ; Freedman, B ; Gasparini, P ; Gieger, C ; Girotto, G ; Goddard, ME ; Golightly, YM ; Gonzalez-Villalpando, C ; Gordon-Larsen, P ; Grallert, H ; Grant, SFA ; Grarup, N ; Griffiths, L ; Gudnason, V ; Haiman, C ; Hakonarson, H ; Hansen, T ; Hartman, CA ; Hattersley, AT ; Hayward, C ; Heckbert, SR ; Heng, C-K ; Hengstenberg, C ; Hewitt, AW ; Hishigaki, H ; Hoyng, CB ; Huang, PL ; Huang, W ; Hunt, SC ; Hveem, K ; Hypponen, E ; Iacono, WG ; Ichihara, S ; Ikram, MA ; Isasi, CR ; Jackson, RD ; Jarvelin, M-R ; Jin, Z-B ; Jockel, K-H ; Joshi, PK ; Jousilahti, P ; Jukema, JW ; Kahonen, M ; Kamatani, Y ; Kang, KD ; Kaprio, J ; Kardia, SLR ; Karpe, F ; Kato, N ; Kee, F ; Kessler, T ; Khera, A ; Khor, CC ; Kiemeney, LALM ; Kim, B-J ; Kim, EK ; Kim, H-L ; Kirchhof, P ; Kivimaki, M ; Koh, W-P ; Koistinen, HA ; Kolovou, GD ; Kooner, JS ; Kooperberg, C ; Kottgen, A ; Kovacs, P ; Kraaijeveld, A ; Kraft, P ; Krauss, RM ; Kumari, M ; Kutalik, Z ; Laakso, M ; Lange, LA ; Langenberg, C ; Launer, LJ ; Le Marchand, L ; Lee, H ; Lee, NR ; Lehtimaki, T ; Li, H ; Li, L ; Lieb, W ; Lin, X ; Lind, L ; Linneberg, A ; Liu, C-T ; Liu, J ; Loeffler, M ; London, B ; Lubitz, SA ; Lye, SJ ; Mackey, DA ; Magi, R ; Magnusson, PKE ; Marcus, GM ; Vidal, PM ; Martin, NG ; Marz, W ; Matsuda, F ; McGarrah, RW ; McGue, M ; McKnight, AJ ; Medland, SE ; Mellstrom, D ; Metspalu, A ; Mitchell, BD ; Mitchell, P ; Mook-Kanamori, DO ; Morris, AD ; Mucci, LA ; Munroe, PB ; Nalls, MA ; Nazarian, S ; Nelson, AE ; Neville, MJ ; Newton-Cheh, C ; Nielsen, CS ; Nothen, MM ; Ohlsson, C ; Oldehinkel, AJ ; Orozco, L ; Pahkala, K ; Pajukanta, P ; Palmer, CNA ; Parra, EJ ; Pattaro, C ; Pedersen, O ; Pennell, CE ; Penninx, BWJH ; Perusse, L ; Peters, A ; Peyser, PA ; Porteous, DJ ; Posthuma, D ; Power, C ; Pramstaller, PP ; Province, MA ; Qi, Q ; Qu, J ; Rader, DJ ; Raitakari, OT ; Ralhan, S ; Rallidis, LS ; Rao, DC ; Redline, S ; Reilly, DF ; Reiner, AP ; Rhee, SY ; Ridker, PM ; Rienstra, M ; Ripatti, S ; Ritchie, MD ; Roden, DM ; Rosendaal, FR ; Rotter, J ; Rudan, I ; Rutters, F ; Sabanayagam, C ; Saleheen, D ; Salomaa, V ; Samani, NJ ; Sanghera, DK ; Sattar, N ; Schmidt, B ; Schmidt, H ; Schmidt, R ; Schulze, MB ; Schunkert, H ; Scott, LJ ; Scott, RJ ; Sever, P ; Shiroma, EJ ; Shoemaker, MB ; Shu, X-O ; Simonsick, EM ; Sims, M ; Singh, JR ; Singleton, AB ; Sinner, MF ; Smith, JG ; Snieder, H ; Spector, TD ; Stampfer, MJ ; Stark, KJ ; Strachan, DP ; t' Hart, LM ; Tabara, Y ; Tang, H ; Tardif, J-C ; Thanaraj, TA ; Timpson, NJ ; Tonjes, A ; Tremblay, A ; Tuomi, T ; Tuomilehto, J ; Tusie-Luna, M-T ; Uitterlinden, AG ; van Dam, RM ; van der Harst, P ; Van der Velde, N ; van Duijn, CM ; van Schoor, NM ; Vitart, V ; Volker, U ; Vollenweider, P ; Volzke, H ; Wacher-Rodarte, NH ; Walker, M ; Wang, YX ; Wareham, NJ ; Watanabe, RM ; Watkins, H ; Weir, DR ; Werge, TM ; Widen, E ; Wilkens, LR ; Willemsen, G ; Willett, WC ; Wilson, JF ; Wong, T-Y ; Woo, J-T ; Wright, AF ; Wu, J-Y ; Xu, H ; Yajnik, CS ; Yokota, M ; Yuan, J-M ; Zeggini, E ; Zemel, BS ; Zheng, W ; Zhu, X ; Zmuda, JM ; Zonderman, AB ; Zwart, J-A ; Chasman, D ; Cho, YS ; Heid, IM ; McCarthy, M ; Ng, MCY ; O'Donnell, CJ ; Rivadeneira, F ; Thorsteinsdottir, U ; Sun, Y ; Tai, ES ; Boehnke, M ; Deloukas, P ; Justice, AE ; Lindgren, CM ; Loos, RJF ; Mohlke, KL ; North, KE ; Stefansson, K ; Walters, RG ; Winkler, TW ; Young, KL ; Loh, P-R ; Yang, J ; Esko, T ; Assimes, TL ; Auton, A ; Abecasis, GR ; Willer, CJ ; Locke, AE ; Berndt, S ; Lettre, G ; Frayling, TM ; Okada, Y ; Wood, AR ; Visscher, PM ; Hirschhorn, JN (NATURE PORTFOLIO, 2022-10-27)
    Common single-nucleotide polymorphisms (SNPs) are predicted to collectively explain 40-50% of phenotypic variation in human height, but identifying the specific variants and associated regions requires huge sample sizes1. Here, using data from a genome-wide association study of 5.4 million individuals of diverse ancestries, we show that 12,111 independent SNPs that are significantly associated with height account for nearly all of the common SNP-based heritability. These SNPs are clustered within 7,209 non-overlapping genomic segments with a mean size of around 90 kb, covering about 21% of the genome. The density of independent associations varies across the genome and the regions of increased density are enriched for biologically relevant genes. In out-of-sample estimation and prediction, the 12,111 SNPs (or all SNPs in the HapMap 3 panel2) account for 40% (45%) of phenotypic variance in populations of European ancestry but only around 10-20% (14-24%) in populations of other ancestries. Effect sizes, associated regions and gene prioritization are similar across ancestries, indicating that reduced prediction accuracy is likely to be explained by linkage disequilibrium and differences in allele frequency within associated regions. Finally, we show that the relevant biological pathways are detectable with smaller sample sizes than are needed to implicate causal genes and variants. Overall, this study provides a comprehensive map of specific genomic regions that contain the vast majority of common height-associated variants. Although this map is saturated for populations of European ancestry, further research is needed to achieve equivalent saturation in other ancestries.
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    Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error
    Fan, Q ; Pozarickij, A ; Tan, NYQ ; Guo, X ; Verhoeven, VJM ; Vitart, V ; Guggenheim, JA ; Miyake, M ; Tideman, JWL ; Khawaja, AP ; Zhang, L ; MacGregor, S ; Hoehn, R ; Chen, P ; Biino, G ; Wedenoja, J ; Saffari, SE ; Tedja, MS ; Xie, J ; Lanca, C ; Wang, YX ; Sahebjada, S ; Mazur, J ; Mirshahi, A ; Martin, NG ; Yazar, S ; Pennell, CE ; Yap, M ; Haarman, AEG ; Enthoven, CA ; Polling, J ; Hewitt, AW ; Jaddoe, VWV ; van Duijn, CM ; Hayward, C ; Polasek, O ; Tai, E-S ; Yoshikatsu, H ; Hysi, PG ; Young, TL ; Tsujikawa, A ; Wang, JJ ; Mitchell, P ; Pfeiffer, N ; Parssinen, O ; Foster, PJ ; Fossarello, M ; Yip, SP ; Williams, C ; Hammond, CJ ; Jonas, JB ; He, M ; Mackey, DA ; Wong, T-Y ; Klaver, CCW ; Saw, S-M ; Baird, PN ; Cheng, C-Y (NATURE PORTFOLIO, 2020-03-19)
    Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.