Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans

Trygve E Bakken, J Cooper Roddey, Srdjan Djurovic, Natacha Akshoomoff, David G Amaral, Cinnamon S Bloss, B J Casey, Linda Chang, Thomas M Ernst, Jeffrey R Gruen, Terry L Jernigan, Walter E Kaufmann, Tal Kenet, David N Kennedy, Joshua M Kuperman, Sarah S Murray, Elizabeth R Sowell, Lars M Rimol, Morten Mattingsdal, Ingrid Melle, Ingrid Agartz, Ole A Andreassen, Nicholas J Schork, Anders M Dale, Michael Weiner, Paul Aisen, Ronald Petersen, Clifford R Jack, William Jagust, John Q Trojanowki, Arthur W Toga, Laurel Beckett, Robert C Green, Andrew J Saykin, John Morris, Enchi Liu, Tom Montine, Anthony Gamst, Ronald G Thomas, Michael Donohue, Sarah Walter, Devon Gessert, Tamie Sather, Danielle Harvey, John Kornak, Anders Dale, Matthew Bernstein, Joel Felmlee, Nick Fox, Paul Thompson, Norbert Schuff, Gene Alexander, Charles DeCarli, Dan Bandy, Robert A Koeppe, Norm Foster, Eric M Reiman, Kewei Chen, Chet Mathis, Nigel J Cairns, Lisa Taylor-Reinwald, J Q Trojanowki, Les Shaw, Virginia M Y Lee, Magdalena Korecka, Karen Crawford, Scott Neu, Tatiana M Foroud, Steven Potkin, Li Shen, Zaven Kachaturian, Richard Frank, Peter J Snyder, Susan Molchan, Jeffrey Kaye, Joseph Quinn, Betty Lind, Sara Dolen, Lon S Schneider, Sonia Pawluczyk, Bryan M Spann, James Brewer, Helen Vanderswag, Judith L Heidebrink, Joanne L Lord, Kris Johnson, Rachelle S Doody, Javier Villanueva-Meyer, Munir Chowdhury, Yaakov Stern, Lawrence S Honig, Karen L Bell, John C Morris, Beau Ances, Maria Carroll, Sue Leon, Mark A Mintun, Stacy Schneider, Daniel Marson, Randall Griffith, David Clark, Hillel Grossman, Effie Mitsis, Aliza Romirowsky, Leyla deToledo-Morrell, Raj C Shah, Ranjan Duara, Daniel Varon, Peggy Roberts, Marilyn Albert, Chiadi Onyike, Stephanie Kielb, Henry Rusinek, Mony J de Leon, Lidia Glodzik, Susan De Santi, P Murali Doraiswamy, Jeffrey R Petrella, R Edward Coleman, Steven E Arnold, Jason H Karlawish, David Wolk, Charles D Smith, Greg Jicha, Peter Hardy, Oscar L Lopez, MaryAnn Oakley, Donna M Simpson, Anton P Porsteinsson, Bonnie S Goldstein, Kim Martin, Kelly M Makino, M Saleem Ismail, Connie Brand, Ruth A Mulnard, Gaby Thai, Catherine Mc-Adams-Ortiz, Kyle Womack, Dana Mathews, Mary Quiceno, Ramon Diaz-Arrastia, Richard King, Myron Weiner, Kristen Martin-Cook, Michael DeVous, Allan I Levey, James J Lah, Janet S Cellar, Jeffrey M Burns, Heather S Anderson, Russell H Swerdlow, Liana Apostolova, Po H Lu, George Bartzokis, Daniel H S Silverman, Neill R Graff-Radford, Francine Parfitt, Heather Johnson, Martin R Farlow, Ann Marie Hake, Brandy R Matthews, Scott Herring, Christopher H van Dyck, Richard E Carson, Martha G MacAvoy, Howard Chertkow, Howard Bergman, Chris Hosein, Sandra Black, Bojana Stefanovic, Curtis Caldwell, Ging-Yuek, Robin Hsiung, Howard Feldman, Benita Mudge, Michele Assaly, Andrew Kertesz, John Rogers, Dick Trost, Charles Bernick, Donna Munic, Diana Kerwin, Marek-Marsel Mesulam, Kristina Lipowski, Chuang-Kuo Wu, Nancy Johnson, Carl Sadowsky, Walter Martinez, Teresa Villena, Raymond Scott Turner, Kathleen Johnson, Brigid Reynolds, Reisa A Sperling, Keith A Johnson, Gad Marshall, Meghan Frey, Jerome Yesavage, Joy L Taylor, Barton Lane, Allyson Rosen, Jared Tinklenberg, Marwan Sabbagh, Christine Belden, Sandra Jacobson, Neil Kowall, Ronald Killiany, Andrew E Budson, Alexander Norbash, Patricia Lynn Johnson, Thomas O Obisesan, Saba Wolday, Salome K Bwayo, Alan Lerner, Leon Hudson, Paula Ogrocki, Evan Fletcher, Owen Carmichael, John Olichney, Smita Kittur, Michael Borrie, T-Y Lee, Rob Bartha, Sterling Johnson, Sanjay Asthana, Cynthia M Carlsson, Steven G Potkin, Adrian Preda, Dana Nguyen, Pierre Tariot, Adam Fleisher, Stephanie Reeder, Vernice Bates, Horacio Capote, Michelle Rainka, Douglas W Scharre, Maria Kataki, Earl A Zimmerman, Dzintra Celmins, Alice D Brown, Godfrey D Pearlson, Karen Blank, Karen Anderson, Robert B Santulli, Eben S Schwartz, Kaycee M Sink, Jeff D Williamson, Pradeep Garg, Franklin Watkins, Brian R Ott, Henry Querfurth, Geoffrey Tremont, Stephen Salloway, Paul Malloy, Stephen Correia, Howard J Rosen, Bruce L Miller, Jacobo Mintzer, Crystal Flynn Longmire, Kenneth Spicer, Elizabether Finger, Irina Rachinsky, Dick Drost, Terry Jernigan, Connor McCabe, Ellen Grant, Thomas Ernst, Josh Kuperman, Yoon Chung, Sarah Murray, Cinnamon Bloss, Burcu Darst, Lexi Pritchett, Ashley Saito, David Amaral, Mishaela DiNino, Bella Eyngorina, Elizabeth Sowell, Suzanne Houston, Lindsay Soderberg, Walter Kaufmann, Peter van Zijl, Hilda Rizzo-Busack, Mohsin Javid, Natasha Mehta, Erika Ruberry, Alisa Powers, Bruce Rosen, Nitzah Gebhard, Holly Manigan, Jean Frazier, David Kennedy, Lauren Yakutis, Michael Hill, Jeffrey Gruen, Joan Bosson-Heenan, Heatherly Carlson

Visual cortical surface area varies two- to threefold between human individuals, is highly heritable, and has been correlated with visual acuity and visual perception. However, it is still largely unknown what specific genetic and environmental factors contribute to normal variation in the area of visual cortex. To identify SNPs associated with the proportional surface area of visual cortex, we performed a genome-wide association study followed by replication in two independent cohorts. We identified one SNP (rs6116869) that replicated in both cohorts and had genome-wide significant association (P(combined) = 3.2 × 10(-8)). Furthermore, a metaanalysis of imputed SNPs in this genomic region identified a more significantly associated SNP (rs238295; P = 6.5 × 10(-9)) that was in strong linkage disequilibrium with rs6116869. These SNPs are located within 4 kb of the 5' UTR of GPCPD1, glycerophosphocholine phosphodiesterase GDE1 homolog (Saccharomyces cerevisiae), which in humans, is more highly expressed in occipital cortex compared with the remainder of cortex than 99.9% of genes genome-wide. Based on these findings, we conclude that this common genetic variation contributes to the proportional area of human visual cortex. We suggest that identifying genes that contribute to normal cortical architecture provides a first step to understanding genetic mechanisms that underlie visual perception.