Top

Published in:

Open Access 01-12-2016 | Original Article

Genetics of structural connectivity and information processing in the brain

Authors: Sudheer Giddaluru, Thomas Espeseth, Alireza Salami, Lars T. Westlye, Anders Lundquist, Andrea Christoforou, Sven Cichon, Rolf Adolfsson, Vidar M. Steen, Ivar Reinvang, Lars Göran Nilsson, Stéphanie Le Hellard, Lars Nyberg

Published in: Brain Structure and Function | Issue 9/2016

Abstract

Understanding the genetic factors underlying brain structural connectivity is a major challenge in imaging genetics. Here, we present results from genome-wide association studies (GWASs) of whole-brain white matter (WM) fractional anisotropy (FA), an index of microstructural coherence measured using diffusion tensor imaging. Data from independent GWASs of 355 Swedish and 250 Norwegian healthy adults were integrated by meta-analysis to enhance power. Complementary GWASs on behavioral data reflecting processing speed, which is related to microstructural properties of WM pathways, were performed and integrated with WM FA results via multimodal analysis to identify shared genetic associations. One locus on chromosome 17 (rs145994492) showed genome-wide significant association with WM FA (meta P value = 1.87 × 10⁻⁰⁸). Suggestive associations (Meta P value <1 × 10⁻⁰⁶) were observed for 12 loci, including one containing ZFPM2 (lowest meta P value = 7.44 × 10⁻⁰⁸). This locus was also implicated in multimodal analysis of WM FA and processing speed (lowest Fisher P value = 8.56 × 10⁻⁰⁷). ZFPM2 is relevant in specification of corticothalamic neurons during brain development. Analysis of SNPs associated with processing speed revealed association with a locus that included SSPO (lowest meta P value = 4.37 × 10⁻⁰⁸), which has been linked to commissural axon growth. An intergenic SNP (rs183854424) 14 kb downstream of CSMD1, which is implicated in schizophrenia, showed suggestive evidence of association in the WM FA meta-analysis (meta P value = 1.43 × 10⁻⁰⁷) and the multimodal analysis (Fisher P value = 1 × 10⁻⁰⁷). These findings provide novel data on the genetics of WM pathways and processing speed, and highlight a role of ZFPM2 and CSMD1 in information processing in the brain.

Available only for authorised users

Ables JL, Breunig JJ, Eisch AJ, Rakic P (2011) Not(ch) just development: notch signalling in the adult brain. Nat Rev Neurosci 12(5):269–283. doi:10.1038/nrn3024 CrossRefPubMedPubMedCentral

Ackermann M, Strimmer K (2009) A general modular framework for gene set enrichment analysis. BMC Bioinformatics 10:47. doi:10.1186/1471-2105-10-47 CrossRefPubMedPubMedCentral

Alitto HJ, Usrey WM (2003) Corticothalamic feedback and sensory processing. Curr Opin Neurobiol 13(4):440–445. doi:10.1016/S0959-4388(03)00096-5 CrossRefPubMed

Andersson JLR, Jenkinson M, Smith S (2007) Non-linear registration aka Spatial normalisation FMRIB Technical Report TR07JA2. Oxford

Aulchenko YS, Ripke S, Isaacs A, van Duijn CM (2007) GenABEL: an R library for genome-wide association analysis. Bioinformatics 23(10):1294–1296. doi:10.1093/bioinformatics/btm108 CrossRefPubMed

Bakken TE, Roddey JC, Djurovic S, Akshoomoff N, Amaral DG, Bloss CS, Carlson H et al (2012) Association of common genetic variants in GPCPD1 with scaling of visual cortical surface area in humans. Proc Natl Acad Sci USA 109(10):3985–3990. doi:10.1073/pnas.1105829109 CrossRefPubMedPubMedCentral

Bartzokis G, Lu PH, Tingus K, Mendez MF, Richard A, Peters DG, Oluwadara B, Barrall KA, Finn JP, Villablanca P, Thompson PM, Mintz J (2010) Lifespan trajectory of myelin integrity and maximum motor speed. Neurobiol Aging 31(9):1554–1562. doi:10.1016/j.neurobiolaging.2008.08.015 CrossRefPubMed

Basser PJ, Pierpaoli C (1996) Microstructural and physiological features of tissues elucidated by quantitative-diffusion-tensor MRI. J Magn Reson 111:209–219. doi:10.1016/j.jmr.2011.09.022 CrossRef

Behrens TEJ, Woolrich MW, Jenkinson M, Johansen-Berg H, Nunes RG, Clare S, Matthews PM, Brady JM, Smith SM (2003) Characterization and propagation of uncertainty in diffusion-weighted MR imaging. Magn Reson Med 50(5):1077–1088. doi:10.1002/mrm.10609 CrossRefPubMed

Bergendal G, Martola J, Stawiarz L, Kristoffersen-Wiberg M, Fredrikson S, Almkvist O (2013) Callosal atrophy in multiple sclerosis is related to cognitive speed. Acta Neurol Scand 127(4):281–289. doi:10.1111/ane.12006 CrossRefPubMed

Boutte D, Calhoun VD, Chen J, Sabbineni A, Hutchison K, Liu J (2012) Association of genetic copy number variations at 11 q14.2 with brain regional volume differences in an alcohol use disorder population. Alcohol 46(6):519–527. doi:10.1016/j.alcohol.2012.05.002.Association CrossRefPubMedPubMedCentral

Briggs F, Usrey WM (2008) Emerging views of corticothalamic function. Curr Opin Neurobiol 18(4):403–407. doi:10.1016/j.conb.2008.09.002 CrossRefPubMedPubMedCentral

Bruno RM, Sakmann B (2006) Cortex is driven by weak but synchronously active thalamocortical synapses. Science 312(5780):1622–1627. doi:10.1126/science.1124593 CrossRefPubMed

Chiang M-C, Barysheva M, Shattuck DW, Lee AD, Madsen SK, Avedissian C, Klunder AD, Toga AW, McMahon KL, de Zubicaray GI, Wright MJ, Srivastava A, Balov N, Thompson PM (2009) Genetics of brain fiber architecture and intellectual performance. J Neurosci 29(7):2212–2224. doi:10.1523/JNEUROSCI.4184-08.2009 CrossRefPubMedPubMedCentral

Chiang M-C, McMahon KL, de Zubicaray GI, Martin NG, Hickie I, Toga AW, Wright MJ, Thompson PM (2011) Genetics of white matter development: a DTI study of 705 twins and their siblings aged 12 to 29. Neuroimage 54(3):2308–2317. doi:10.1016/j.neuroimage.2010.10.015 CrossRefPubMed

Christoforou A, Dondrup M, Mattingsdal M, Mattheisen M, Giddaluru S, Nöthen MM, Rietschel M, Cichon S, Djurovic S, Andreassen OA, Jonassen I, Steen VM, Puntervoll P, Le Hellard S (2012) Linkage-disequilibrium-based binning affects the interpretation of GWASs. Am J Hum Genet 90(4):727–733. doi:10.1016/j.ajhg.2012.02.025 CrossRefPubMedPubMedCentral

Deck M, Lokmane L, Chauvet S, Mailhes C, Keita M, Niquille M, Yoshida M, Yoshida Y, Lebrand C, Mann F, Grove EA, Garel S (2013) Pathfinding of corticothalamic axons relies on a rendezvous with thalamic projections. Neuron 77(3):472–484. doi:10.1016/j.neuron.2012.11.031 CrossRefPubMedPubMedCentral

Ersland KM, Christoforou A, Stansberg C, Espeseth T, Mattheisen M, Mattingsdal M, Hardarson GA, Hansen T, Fernandes CPD, Giddaluru S, Breuer R, Strohmaier J, Djurovic S, Nöthen MM, Rietschel M, Lundervold AJ, Werge T, Cichon S, Andreassen OA, Reinvang I, Steen VM, Le Hellard S (2012) Gene-based analysis of regionally enriched cortical genes in GWAS data sets of cognitive traits and psychiatric disorders. PLoS One 7(2):e31687. doi:10.1371/journal.pone.0031687 CrossRefPubMedPubMedCentral

Espeseth T, Christoforou A, Lundervold AJ, Steen VM, Le Hellard S, Reinvang I (2012) Imaging and cognitive genetics: the Norwegian Cognitive NeuroGenetics sample. Twin Res Hum Genet 15(3):442–452. doi:10.1017/thg.2012.8 CrossRefPubMed

Fernandes CPD, Christoforou A, Giddaluru S, Ersland KM, Djurovic S, Mattheisen M, Lundervold AJ, Reinvang I, Nöthen MM, Rietschel M, Ophoff RA, Hofman A, Uitterlinden AG, Werge T, Cichon S, Espeseth T, Andreassen OA, Steen VM, Le Hellard S (2013) A genetic deconstruction of neurocognitive traits in schizophrenia and bipolar disorder. PLoS One 8(12):e81052. doi:10.1371/journal.pone.0081052 CrossRefPubMedPubMedCentral

Fernandes CPD, Westlye LT, Giddaluru S, Christoforou A, Kauppi K, Adolfsson R, Nilsson L-G, Nyberg L, Lundervold AJ, Reinvang I, Steen VM, Le Hellard S, Espeseth T (2014) Lack of association of the rs1344706 ZNF804A variant with cognitive functions and DTI indices of white matter microstructure in two independent healthy populations. Psychiatry Res Neuroimaging 222(1–2):60–66CrossRefPubMed

Fisher RA (1932) Statistical Methodsfor Research Workers, 4th edn. Oliver and Boyd, Edinburgh

Fjell AM, Westlye LT, Amlien IK, Walhovd KB (2011) Reduced white matter integrity is related to cognitive instability. J Neurosci 31(49):18060–18072. doi:10.1523/JNEUROSCI.4735-11.2011 CrossRefPubMed

Gold BT, Powell DK, Xuan L, Jiang Y, Hardy PA (2007) Speed of lexical decision correlates with diffusion anisotropy in left parietal and frontal white matter: evidence from diffusion tensor imaging. Neuropsychologia 45(11):2439–2446. doi:10.1016/j.neuropsychologia.2007.04.011 CrossRefPubMedPubMedCentral

Grondona JM, Hoyo-Becerra C, Visser R, Fernández-Llebrez P, López-Ávalos MD (2012) The subcommissural organ and the development of the posterior commissure. In: International review of cell and molecular biology. pp 63–137

Haász J, Westlye ET, Fjær S, Espeseth T, Lundervold A, Lundervold AJ (2013) General fluid-type intelligence is related to indices of white matter structure in middle-aged and old adults. Neuroimage 83:372–383. doi:10.1016/j.neuroimage.2013.06.040 CrossRefPubMed

Håvik B, Le Hellard S, Rietschel M, Lybæk H, Djurovic S, Mattheisen M, Mühleisen TW, Degenhardt F, Priebe L, Maier W, Breuer R, Schulze TG, Agartz I, Melle I, Hansen T, Bramham CR, Nöthen MM, Stevens B, Werge T, Andreassen OA, Cichon S, Steen VM (2011) The complement control-related genes CSMD1 and CSMD2 associate to schizophrenia. Biol Psychiatry 70(1):35–42. doi:10.1016/j.biopsych.2011.01.030 CrossRefPubMed

Heise V, Filippini N, Ebmeier KPMC (2011) The APOE ɛ4 allele modulates brain white matter integrity in healthy adults. Mol Psychiatry 16(9):908–916. doi:10.1038/mp.2010.90 CrossRefPubMed

Hibar D, Stein J, Renteria M, Arias-Vasquez A, Desrivières S, Jahanshad N, Medland S et al (2015) Common genetic variants influence human subcortical brain structures. Nature 520(7546):224–229. doi:10.1038/nature14101 CrossRefPubMedPubMedCentral

Howie B, Fuchsberger C, Stephens M, Marchini J, Abecasis GR (2012) Fast and accurate genotype imputation in genome-wide association studies through pre-phasing. Nat Genet 44(8):955–959. doi:10.1038/ng.2354 CrossRefPubMedPubMedCentral

Hyun S, Lee JH, Jin H, Nam J, Namkoong B, Lee G, Chung J, Kim VN (2009) Conserved MicroRNA miR-8/miR-200 and its target USH/FOG2 control growth by regulating PI3K. Cell 139(6):1096–1108. doi:10.1016/j.cell.2009.11.020 CrossRefPubMed

Ibrahim-Verbaas CA, Bressler J, Debette S, Schuur M, Smith AV, Bis JC, Mosley TH et al (2015) GWAS for executive function and processing speed suggests involvement of the CADM2 gene. Mol Psychiatry. doi:10.1038/mp.2015.37

Iverson GL, Hakulinen U, Wäljas M, Dastidar P, Lange RT, Soimakallio S, Öhman J (2011) To exclude or not to exclude: white matter hyperintensities in diffusion tensor imaging research. Brain Inj 25(13–14):1325–1332. doi:10.3109/02699052.2011.608409 CrossRefPubMed

Jahanshad N, Kochunov P, Sprooten E, Mandl RC, Nichols TE, Almassy L, Blangero J, Brouwer RM, Curran JE, de Zubicaray GI, Duggirala R, Fox PT, Hong LE, Landman BA, Martin NG, McMahon KL, Medland SE, Mitchell BD, Olvera RL, Peterson CP, Starr JM, Sussmann JE, Toga AW, Wardlaw JM, Wright MJ, Hulshoff Pol HE, Bastin ME, McIntosh AM, Deary IJ, Thompson PM, Glahn DC (2013a) Multi-site genetic analysis of diffusion images and voxelwise heritability analysis: a pilot project of the ENIGMA-DTI working group. Neuroimage 81:455–469. doi:10.1016/j.neuroimage.2013.04.061 CrossRefPubMedPubMedCentral

Jahanshad N, Rajagopalan P, Hua X, Hibar DP, Nir TM, Toga AW, Jack CR, Saykin AJ, Green RC, Weiner MW, Medland SE, Montgomery GW, Hansell NK, Mcmahon KL, De Zubicaray GI, Martin NG, Wright MJ, Thompson PM, Alzheimer’s Disease Neuroimaging Initiative (2013b) Genome-wide scan of healthy human connectome discovers SPON1 gene variant influencing dementia severity. Proc Natl Acad Sci USA 110(12):4768–4773. doi:10.1073/pnas.1216206110 CrossRefPubMedPubMedCentral

Jenkinson M, Bannister P, Brady M, Smith S (2002) Improved optimization for the robust and accurate linear registration and motion correction of brain images. Neuroimage 17(2):825–841. doi:10.1006/nimg.2002.1132 CrossRefPubMed

Kail R, Salthouse TA (1994) Processing speed as a mental capacity. Acta Psychol (Amst) 86:199–225CrossRef

Karbasforoushan H, Duffy B, Blackford JU, Woodward ND (2015) Processing speed impairment in schizophrenia is mediated by white matter integrity. Psychol Med 45(1):109–120. doi:10.1017/S0033291714001111 CrossRefPubMed

Kennedy KM, Raz N (2009) Aging white matter and cognition: differential effects of regional variations in diffusion properties on memory, executive functions, and speed. Neuropsychologia 47(3):916–927. doi:10.1016/j.neuropsychologia.2009.01.001 CrossRefPubMedPubMedCentral

Kochunov P, Glahn DC, Lancaster JL, Winkler AM, Smith S, Thompson PM, Almasy L, Duggirala R, Fox PT, Blangero J (2010a) Genetics of microstructure of cerebral white matter using diffusion tensor imaging. Neuroimage 53(3):1109–1116. doi:10.1016/j.neuroimage.2010.01.078 CrossRefPubMedPubMedCentral

Kochunov P, Coyle T, Lancaster J, Robin DA, Hardies J, Kochunov V, Bartzokis G, Stanley J, Royall D, Schlosser AE, Null M, Fox PT (2010b) Processing speed is correlated with cerebral health markers in the frontal lobes as quantified by neuroimaging. Neuroimage 49(2):1190–1199. doi:10.1016/j.neuroimage.2009.09.052 CrossRefPubMed

Kochunov P, Jahanshad N, Marcus D, Winkler A, Sprooten E, Nichols TE, Van Essen DC et al (2015) Heritability of fractional anisotropy in human white matter: a comparison of human connectome project and ENIGMA-DTI data. Neuroimage 111:300–311. doi:10.1016/j.neuroimage.2015.02.050 CrossRefPubMedPubMedCentral

Kochunov P, Thompson PM, Winkler A, Morrissey M, Fu M, Coyle TR, Du X, Muellerklein F, Savransky A, Gaudiot C, Sampath H, Eskandar G, Jahanshad N, Patel B, Rowland L, Nichols TE, O’Connell JR, Shuldiner AR, Mitchell BD, Hong LE (2016) The common genetic influence over processing speed and white matter microstructure: evidence from the Old Order Amish and Human Connectome Projects. Neuroimage 125:189–197. doi:10.1016/j.neuroimage.2015.10.050 CrossRefPubMed

Kwan KY, Lam MMS, Krsnik Z, Kawasawa YI, Lefebvre V, Sestan N (2008) SOX5 postmitotically regulates migration, postmigratory differentiation, and projections of subplate and deep-layer neocortical neurons. Proc Natl Acad Sci USA 105(41):16021–16026. doi:10.1073/pnas.0806791105 CrossRefPubMedPubMedCentral

Li Y, Willer C, Sanna S, Abecasis G (2009) Genotype imputation. Annu Rev Genomics Hum Genet 10:387–406. doi:10.1146/annurev.genom.9.081307.164242.Genotype CrossRefPubMedPubMedCentral

Li Y, Willer CJ, Ding J, Scheet P, Abecasis GR (2010) MaCH: using sequence and genotype data to estimate haplotypes and unobserved genotypes. Genet Epidemiol 34(8):816–834. doi:10.1002/gepi.20533 CrossRefPubMedPubMedCentral

Liu YJ, Papasian CJ, Liu JF, Hamilton J, Deng HW (2008) Is replication the gold standard for validating genome-wide association findings? PLoS One 3(12):e4037. doi:10.1371/journal.pone.0004037 CrossRefPubMedPubMedCentral

Lopez LM, Bastin ME, Maniega SM, Penke L, Davies G, Christoforou A, Valdés Hernández MC, Royle NA, Tenesa A, Starr JM, Porteous DJ, Wardlaw JM, Deary IJ (2012) A genome-wide search for genetic influences and biological pathways related to the brain’s white matter integrity. Neurobiol Aging 33(8):1847.e1–1847.e14. doi:10.1016/j.neurobiolaging.2012.02.003 CrossRef

Lu JR, McKinsey TA, Xu H, Wang DZ, Richardson JA, Olson EN (1999) FOG-2, a heart- and brain-enriched cofactor for GATA transcription factors. Mol Cell Biol 19(6):4495–4502CrossRefPubMedPubMedCentral

Luciano M, Gow AJ, Harris SE, Hayward C, Allerhand M, Starr JM, Visscher PM, Deary IJ (2009) Cognitive ability at age 11 and 70 years, information processing speed, and APOE variation: the Lothian Birth Cohort 1936 study. Psychol Aging 24(1):129–138. doi:10.1037/a0014780 CrossRefPubMed

Madden DJ, Bennett IJ, Burzynska A, Potter GG, Chen N-K, Song AW (2012) Diffusion tensor imaging of cerebral white matter integrity in cognitive aging. Biochim Biophys Acta 1822(3):386–400. doi:10.1016/j.bbadis.2011.08.003 CrossRefPubMed

McAllister TW, Tyler AL, Flashman LA, Rhodes CH, McDonald BC, Saykin AJ, Tosteson TD, Tsongalis GJ, Moore JH (2012) Polymorphisms in the brain-derived neurotrophic factor gene influence memory and processing speed one month after brain injury. J Neurotrauma 29(6):1111–1118. doi:10.1089/neu.2011.1930 CrossRefPubMedPubMedCentral

McClearn GE, Johansson B, Berg S, Pedersen NL, Ahern F, Petrill SA, Plomin R (1997) Substantial genetic influence on cognitive abilities in twins 80 or more years old. Science 276(5318):1560–1563. doi:10.1126/science.276.5318.1560 CrossRefPubMed

Mochizuki Y, Majerus PW (2003) Characterization of myotubularin-related protein 7 and its binding partner, myotubularin-related protein 9. Proc Natl Acad Sci USA 100(17):9768–9773. doi:10.1073/pnas.1333958100 CrossRefPubMedPubMedCentral

Mootha VK, Lindgren CM, Eriksson K-F, Subramanian A, Sihag S, Lehar J, Puigserver P, Carlsson E, Ridderstråle M, Laurila E, Houstis N, Daly MJ, Patterson N, Mesirov JP, Golub TR, Tamayo P, Spiegelman B, Lander ES, Hirschhorn JN, Altshuler D, Groop LC (2003) PGC-1alpha-responsive genes involved in oxidative phosphorylation are coordinately downregulated in human diabetes. Nat Genet 34(3):267–273. doi:10.1038/ng1180 CrossRefPubMed

Mounce J, Luo L, Caprihan A, Liu J, Perrone-Bizzozero NI, Calhoun VD (2014) Association of GRM3 polymorphism with white matter integrity in schizophrenia. Schizophr Res 155(1–3):8–14. doi:10.1016/j.schres.2014.03.003 CrossRefPubMedPubMedCentral

Nielsen JV, Thomassen M, Møllgård K, Noraberg J, Jensen NA (2013) zbtb20 defines a hippocampal neuronal identity through direct repression of genes that control projection neuron development in the isocortex. Cereb Cortex 24(5):1216–1229. doi:10.1093/cercor/bhs400 CrossRefPubMed

Nilsson L-G, Bäckman L, Erngrund K, Nyberg L, Adolfsson R, Bucht G, Karlsson S, Widing M, Winblad B (1997) The betula prospective cohort study: memory, health, and aging. Aging Neuropsychol Cogn 4(1):1–32. doi:10.1080/13825589708256633 CrossRef

Nilsson L-G, Adolfsson R, Bäckman L, de Frias CM, Molander B, Nyberg L (2004) Betula : a prospective cohort study on memory, health and aging betula: a prospective cohort study on memory, health and aging. Aging Neuropsychol Cogn 11(2–3):134–148. doi:10.1080/13825580490511026 CrossRef

Nilsson L-G, Söderlund H, Berger K, Breteler M, de Ridder M, Dufouil C, Fuhrer R, Giampaoli S, Hofman A, Pajak A, Sans S, Schmidt R, Launer LJ (2005) Cognitive test battery of CASCADE: tasks and data. Aging Neuropsychol Cogn 12(1):32–56. doi:10.1080/13825580590925099 CrossRef

Nyberg L, Salami A (2014) The APOE ε4 allele in relation to brain white-matter microstructure in adulthood and aging. Scand J Psychol 55(3):263–267. doi:10.1111/sjop.12099 CrossRefPubMed

Pei YF, Zhang L, Papasian CJ, Wang YP, Deng HW (2014) On individual genome-wide association studies and their meta-analysis. Hum Genet 133(3):265–279. doi:10.1007/s00439-013-1366-4 CrossRefPubMed

Penke L, Muñoz Maniega S, Houlihan LM, Murray C, Gow AJ, Clayden JD, Bastin ME, Wardlaw JM, Deary IJ (2010) White matter integrity in the splenium of the corpus callosum is related to successful cognitive aging and partly mediates the protective effect of an ancestral polymorphism in ADRB2. Behav Genet 40(2):146–156. doi:10.1007/s10519-009-9318-4 CrossRefPubMed

Pérez MJ, Fernandez N, Pasquini JM (2013) Oligodendrocyte differentiation and signaling after transferrin internalization: a mechanism of action. Exp Neurol 248:262–274. doi:10.1016/j.expneurol.2013.06.014 CrossRefPubMed

Pierpaoli C, Basser PJ (1996) Toward a quantitative assessment of diffusion anisotropy. Magn Reson Med 36(6):893–906CrossRefPubMed

Potkin SG, Guffanti G, Lakatos A, Turner JA, Kruggel F, Fallon JH, Saykin AJ, Orro A, Lupoli S, Salvi E, Weiner M, Macciardi F (2009) Hippocampal atrophy as a quantitative trait in a genome-wide association study identifying novel susceptibility genes for Alzheimer’s disease. PLoS One 4(8):e6501. doi:10.1371/journal.pone.0006501 CrossRefPubMedPubMedCentral

Pruim RJ, Welch RP, Sanna S, Teslovich TM, Chines PS, Gliedt TP, Boehnke M, Abecasis GR, Willer CJ (2010) LocusZoom: regional visualization of genome-wide association scan results. Bioinformatics 26(18):2336–2337. doi:10.1093/bioinformatics/btq419 CrossRefPubMedPubMedCentral

Purcell S, Neale B, Todd-Brown K, Thomas L, Ferreira MAR, Bender D, Maller J, Sklar P, de Bakker PIW, Daly MJ, Sham PC (2007) PLINK: a tool set for whole-genome association and population-based linkage analyses. Am J Hum Genet 81(3):559–575. doi:10.1086/519795 CrossRefPubMedPubMedCentral

Raychaudhuri S, Korn JM, McCarroll SA, Altshuler D, Sklar P, Purcell S, Daly MJ (2010) Accurately assessing the risk of schizophrenia conferred by rare copy-number variation affecting genes with brain function. PLoS Genet 6(9):e1001097. doi:10.1371/journal.pgen.1001097 CrossRefPubMedPubMedCentral

Rimol LM, Panizzon MS, Fennema-Notestine C, Eyler LT, Fischl B, Franz CE, Hagler DJ, Lyons MJ, Neale MC, Pacheco J, Perry ME, Schmitt JE, Grant MD, Seidman LJ, Thermenos HW, Tsuang MT, Eisen SA, Kremen WS, Dale AM (2010) Cortical thickness is influenced by regionally specific genetic factors. Biol Psychiatry 67(5):493–499. doi:10.1016/j.biopsych.2009.09.032 CrossRefPubMed

Ripke S, Neale BM, Corvin A, Walters JTR, Farh K-H, Holmans PA, O’Donovan MC et al (2014) Biological insights from 108 schizophrenia-associated genetic loci. Nature 511(7510):421–427. doi:10.1038/nature13595 CrossRefPubMedCentral

Saccone SF, Hinrichs AL, Saccone NL, Chase GA, Konvicka K, Madden PAF, Breslau N, Johnson EO, Hatsukami D, Pomerleau O, Swan GE, Goate AM, Rutter J, Bertelsen S, Fox L, Fugman D, Martin NG, Montgomery GW, Wang JC, Ballinger DG, Rice JP, Bierut LJ (2007) Cholinergic nicotinic receptor genes implicated in a nicotine dependence association study targeting 348 candidate genes with 3713 SNPs. Hum Mol Genet 16(1):36–49. doi:10.1093/hmg/ddl438 CrossRefPubMed

Salami A, Eriksson J, Nilsson L-G, Nyberg L (2012) Age-related white matter microstructural differences partly mediate age-related decline in processing speed but not cognition. Biochim Biophys Acta 1822(3):408–415. doi:10.1016/j.bbadis.2011.09.001 CrossRefPubMed

Scheib JL, Sullivan CS, Carter BD (2012) Jedi-1 and MEGF10 signal engulfment of apoptotic neurons through the tyrosine kinase Syk. J Neurosci 32(38):13022–13031. doi:10.1523/JNEUROSCI.6350-11.2012.Jedi-1 CrossRefPubMedPubMedCentral

Singh TD, Park S-Y, Bae J, Yun Y, Bae Y-C, Park R-W, Kim I-S (2010) MEGF10 functions as a receptor for the uptake of amyloid-β. FEBS Lett 584(18):3936–3942. doi:10.1016/j.febslet.2010.08.050 CrossRefPubMed

Skol AD, Scott LJ, Abecasis GR, Boehnke M (2006) Joint analysis is more efficient than replication-based analysis for two-stage genome-wide association studies. Nat Genet 38(2):209–213. doi:10.1038/ng1706 CrossRefPubMed

Smith SM, Nichols TE (2009) Threshold-free cluster enhancement: addressing problems of smoothing, threshold dependence and localisation in cluster inference. Neuroimage 44(1):83–98. doi:10.1016/j.neuroimage.2008.03.061 CrossRefPubMed

Smith SM, Jenkinson M, Woolrich MW, Beckmann CF, Behrens TEJ, Johansen-Berg H, Bannister PR, De Luca M, Drobnjak I, Flitney DE, Niazy RK, Saunders J, Vickers J, Zhang Y, De Stefano N, Brady JM, Matthews PM (2004) Advances in functional and structural MR image analysis and implementation as FSL. Neuroimage 23:S208–S219. doi:10.1016/j.neuroimage.2004.07.051 CrossRefPubMed

Smith SM, Jenkinson M, Johansen-Berg H, Rueckert D, Nichols TE, Mackay CE, Watkins KE, Ciccarelli O, Cader MZ, Matthews PM, Behrens TEJ (2006) Tract-based spatial statistics: voxelwise analysis of multi-subject diffusion data. Neuroimage 31(4):1487–1505. doi:10.1016/j.neuroimage.2006.02.024 CrossRefPubMed

Söderlund H, Nyberg L, Adolfsson R, Nilsson L-G, Launer LJ (2003) High prevalence of white matter hyperintensities in normal aging: relation to blood pressure and cognition. Cortex 39:1093–1105CrossRefPubMed

Song S, Black MA (2008) Microarray-based gene set analysis: a comparison of current methods. BMC Bioinformatics 9:502. doi:10.1186/1471-2105-9-502 CrossRefPubMedPubMedCentral

Spencer JPE (2008) Flavonoids: modulators of brain function?. Br J Nutr 99 E Suppl:ES60–77. doi: 10.1017/S0007114508965776

Sprooten E, Fleming KM, Thomson PA, Bastin ME, Whalley HC, Hall J, Sussmann JE, McKirdy J, Blackwood D, Lawrie SM, McIntosh AM (2013) White matter integrity as an intermediate phenotype: exploratory genome-wide association analysis in individuals at high risk of bipolar disorder. Psychiatry Res 206(2–3):223–231. doi:10.1016/j.psychres.2012.11.002 CrossRefPubMed

Sprooten E, Knowles EE, McKay DR, Göring HH, Curran JE, Kent JW, Carless MA, Dyer TD, Drigalenko EI, Olvera RL, Fox PT, Almasy L, Duggirala R, Kochunov P, Blangero J, Glahn DC (2014) Common genetic variants and gene expression associated with white matter microstructure in the human brain. Neuroimage 97:252–261. doi:10.1016/j.neuroimage.2014.04.021 CrossRefPubMedPubMedCentral

Steen VM, Nepal C, Ersland KM, Holdhus R, Nævdal M, Ratvik SM, Skrede S, Håvik B (2013) Neuropsychological deficits in mice depleted of the schizophrenia susceptibility gene CSMD1. PLoS One 8(11):e79501. doi:10.1371/journal.pone.0079501 CrossRefPubMedPubMedCentral

Stein JL, Medland SE, Vasquez AA, Hibar DP, Senstad RE, Winkler AM, Thompson PM et al (2012) Identification of common variants associated with human hippocampal and intracranial volumes. Nat Genet 44(5):552–561. doi:10.1038/ng.2250 CrossRefPubMedPubMedCentral

Subramanian A, Tamayo P, Mootha VK, Mukherjee S, Ebert BL, Gillette MA, Paulovich A, Pomeroy SL, Golub TR, Lander ES, Mesirov JP (2005) Gene set enrichment analysis : a knowledge-based approach for interpreting genome-wide. PNAS 102(43):15545–15550CrossRefPubMedPubMedCentral

Tamnes CK, Fjell AM, Westlye LT, Østby Y, Walhovd KB (2012) Becoming consistent: developmental reductions in intraindividual variability in reaction time are related to white matter integrity. J Neurosci 32(3):972–982. doi:10.1523/JNEUROSCI.4779-11.2012 CrossRefPubMed

Tessier-Lavigne M, Goodman CS (1996) The Molecular Biology of Axon Guidance. Science 274:1123–1133CrossRefPubMed

Thomason ME, Thompson PM (2011) Diffusion imaging, white matter, and psychopathology. Annu Rev Clin Psychol 7:63–85. doi:10.1146/annurev-clinpsy-032210-104507 CrossRefPubMed

Thompson PM, Cannon TD, Narr KL, van Erp T, Poutanen VP, Huttunen M, Lönnqvist J, Standertskjöld-Nordenstam CG, Kaprio J, Khaledy M, Dail R, Zoumalan CI, Toga AW (2001) Genetic influences on brain structure. Nat Neurosci 4(12):1253–1258. doi:10.1038/nn758 CrossRefPubMed

Thompson PM, Stein JL, Medland SE, Hibar DP, Vasquez AA, Renteria ME, Drevets W et al (2014) The ENIGMA Consortium: large-scale collaborative analyses of neuroimaging and genetic data. Brain Imaging Behav 8(2):153–182. doi:10.1007/s11682-013-9269-5 PubMedPubMedCentral

Tuch DS, Salat DH, Wisco JJ, Zaleta AK, Hevelone ND, Rosas HD (2005) Choice reaction time performance correlates with diffusion anisotropy in white matter pathways supporting visuospatial attention. Proc Natl Acad Sci USA 102(34):12212–12217. doi:10.1073/pnas.0407259102 CrossRefPubMedPubMedCentral

Turken AU, Whitfield-Gabrieli S, Bammer R, Baldo JV, Dronkers NF, Gabrieli JDE (2008) Cognitive processing speed and the structure of white matter pathways: convergent evidence from normal variation and lesion studies. Neuroimage 42(2):1032–1044. doi:10.1016/j.neuroimage.2008.03.057 CrossRefPubMedPubMedCentral

van Es MA, Van Vught PW, Blauw HM, Franke L, Saris CG, Andersen PM, Van Den Bosch L, de Jong SW, van’t Slot R, Birve A, Lemmens R, de Jong V, Baas F, Schelhaas HJ, Sleegers K, Van Broeckhoven C, Wokke JHJ, Wijmenga C, Robberecht W, Veldink JH, Ophoff RA, van den Berg LH (2007) ITPR2 as a susceptibility gene in sporadic amyotrophic lateral sclerosis: a genome-wide association study. Lancet Neurol 6:869–77. doi: 10.1016/S1474-4422(07)70222-3

Voineskos AN, Lerch JP, Felsky D, Tiwari A, Rajji TK, Miranda D, Lobaugh NJ, Pollock BG, Mulsant BH, Kennedy JL (2011) The ZNF804A gene: characterization of a novel neural risk mechanism for the major psychoses. Neuropsychopharmacology 36(9):1871–1878. doi:10.1038/npp.2011.72 CrossRefPubMedPubMedCentral

Wang L, Jia P, Wolfinger RD, Chen X, Zhao Z (2011) Gene set analysis of genome-wide association studies: methodological issues and perspectives. Genomics 98(1):1–8. doi:10.1016/j.ygeno.2011.04.006 CrossRefPubMed

Wechsler D (1981) WAIS-R manual: Wechsler adult intelligence scale-revised. Psychological Corporation

Wei Q, Kang Z, Diao F, Guidon A, Wu X, Zheng L, Li L, Guo X, Hu M, Zhang J, Liu C, Zhao J (2012) No association of ZNF804A rs1344706 with white matter integrity in schizophrenia: a tract-based spatial statistics study. Neurosci Lett 532:64–69. doi:10.1016/j.neulet.2012.10.062 CrossRefPubMedPubMedCentral

Westlye LT, Walhovd KB, Dale AM, Bjørnerud A, Due-Tønnessen P, Engvig A, Grydeland H, Tamnes CK, Ostby Y, Fjell AM (2010) Life-span changes of the human brain white matter: diffusion tensor imaging (DTI) and volumetry. Cereb Cortex 20(9):2055–2068. doi:10.1093/cercor/bhp280 CrossRefPubMed

Westlye LT, Reinvang I, Rootwelt H, Espeseth T (2012) Effects of APOE on brain white matter microstructure in healthy adults. Neurology 79(19):1961–1969. doi:10.1212/WNL.0b013e3182735c9c CrossRefPubMed

Willer CJ, Li Y, Abecasis GR (2010) METAL: fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26(17):2190–2191. doi:10.1093/bioinformatics/btq340 CrossRefPubMedPubMedCentral

Wright S, Hong L, Winkler A, Chiappelli J, Nugent K, Muellerklein F, Du X, Rowland L, Wang D, Kochunov P (2015) Perfusion shift from white to gray matter may account for processing speed deficits in schizophrenia. Hum Brain Mapp 36(10):3793–3804CrossRefPubMedPubMedCentral

Title: Genetics of structural connectivity and information processing in the brain
Authors: Sudheer Giddaluru
Thomas Espeseth
Alireza Salami
Lars T. Westlye
Anders Lundquist
Andrea Christoforou
Sven Cichon
Rolf Adolfsson
Vidar M. Steen
Ivar Reinvang
Lars Göran Nilsson
Stéphanie Le Hellard
Lars Nyberg
Publication date: 01-12-2016
Publisher: Springer Berlin Heidelberg
Published in: Brain Structure and Function / Issue 9/2016
Print ISSN: 1863-2653
Electronic ISSN: 1863-2661
DOI: https://doi.org/10.1007/s00429-016-1194-0

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Genetics of structural connectivity and information processing in the brain

Abstract

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 9/2016

Attentional function and basal forebrain cholinergic neuron morphology during aging in the Ts65Dn mouse model of Down syndrome

mGluR4-containing corticostriatal terminals: synaptic interactions with direct and indirect pathway neurons in mice

Tyrosine hydroxylase localization in the nucleus accumbens in schizophrenia

Alcohol dependence-induced regulation of the proliferation and survival of adult brain progenitors is associated with altered BDNF-TrkB signaling

Dorsal and ventral aspects of the most caudal medullary reticular formation have differential roles in modulation and formation of the respiratory motor pattern in rat

Erratum to: Anosmin-1 over-expression increases adult neurogenesis in the subventricular zone and neuroblast migration to the olfactory bulb