Dataset Information

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

ABSTRACT: 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.

SUBMITTER: Bakken TE

PROVIDER: S-EPMC3309762 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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

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

Proceedings of the National Academy of Sciences of the United States of America 20120216 10

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 ident ...[more]

PMID: 22343285

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Project description:ImportanceSchizophrenia is a complex heritable disorder associated with many genetic variants, each with a small effect. While cortical differences between patients with schizophrenia and healthy controls are consistently reported, the underlying molecular mechanisms remain elusive.ObjectiveTo investigate the extent of shared genetic architecture between schizophrenia and brain cortical surface area (SA) and thickness (TH) and to identify shared genomic loci.Design, setting, and participantsIndependent genome-wide association study data on schizophrenia (Psychiatric Genomics Consortium and CLOZUK: n = 105 318) and SA and TH (UK Biobank: n = 33 735) were obtained. The extent of polygenic overlap was investigated using MiXeR. The specific shared genomic loci were identified by conditional/conjunctional false discovery rate analysis and were further examined in 3 independent cohorts. Data were collected from December 2019 to February 2021, and data analysis was performed from May 2020 to February 2021.Main outcomes and measuresThe primary outcomes were estimated fractions of polygenic overlap between schizophrenia, total SA, and average TH and a list of functionally characterized shared genomic loci.ResultsBased on genome-wide association study data from 139 053 participants, MiXeR estimated schizophrenia to be more polygenic (9703 single-nucleotide variants [SNVs]) than total SA (2101 SNVs) and average TH (1363 SNVs). Most SNVs associated with total SA (1966 of 2101 [93.6%]) and average TH (1322 of 1363 [97.0%]) may be associated with the development of schizophrenia. Subsequent conjunctional false discovery rate analysis identified 44 and 23 schizophrenia risk loci shared with total SA and average TH, respectively. The SNV associations of shared loci between schizophrenia and total SA revealed en masse concordant association between the discovery and independent cohorts. After removing high linkage disequilibrium regions, such as the major histocompatibility complex region, the shared loci were enriched in immunologic signature gene sets. Polygenic overlap and shared loci between schizophrenia and schizophrenia-associated regions of interest for SA (superior frontal and middle temporal gyri) and for TH (superior temporal, inferior temporal, and superior frontal gyri) were also identified.Conclusions and relevanceThis study demonstrated shared genetic loci between cortical morphometry and schizophrenia, among which a subset are associated with immunity. These findings provide an insight into the complex genetic architecture and associated with schizophrenia.

Project description:Various types of neural-based signals, such as EEG, local field potentials and intracellular synaptic potentials, integrate multiple sources of activity distributed across large assemblies. They have in common a power-law frequency-scaling structure at high frequencies, but it is still unclear whether this scaling property is dominated by intrinsic neuronal properties or by network activity. The latter case is particularly interesting because if frequency-scaling reflects the network state it could be used to characterize the functional impact of the connectivity. In intracellularly recorded neurons of cat primary visual cortex in vivo, the power spectral density of V(m) activity displays a power-law structure at high frequencies with a fractional scaling exponent. We show that this exponent is not constant, but depends on the visual statistics used to drive the network. To investigate the determinants of this frequency-scaling, we considered a generic recurrent model of cortex receiving a retinotopically organized external input. Similarly to the in vivo case, our in computo simulations show that the scaling exponent reflects the correlation level imposed in the input. This systematic dependence was also replicated at the single cell level, by controlling independently, in a parametric way, the strength and the temporal decay of the pairwise correlation between presynaptic inputs. This last model was implemented in vitro by imposing the correlation control in artificial presynaptic spike trains through dynamic-clamp techniques. These in vitro manipulations induced a modulation of the scaling exponent, similar to that observed in vivo and predicted in computo. We conclude that the frequency-scaling exponent of the V(m) reflects stimulus-driven correlations in the cortical network activity. Therefore, we propose that the scaling exponent could be used to read-out the "effective" connectivity responsible for the dynamical signature of the population signals measured at different integration levels, from Vm to LFP, EEG and fMRI.

Dataset Information

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

Publications

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

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