Abstract
Height and general cognitive ability are positively associated, but the underlying mechanisms of this relationship are not well understood. Both height and general cognitive ability are positively associated with brain size. Still, the neural substrate of the height-cognitive ability association is unclear. We used a sample of 515 middle-aged male twins with structural magnetic resonance imaging data to investigate whether the association between height and cognitive ability is mediated by cortical size. In addition to cortical volume, we used genetically, ontogenetically and phylogenetically distinct cortical metrics of total cortical surface area and mean cortical thickness. Height was positively associated with general cognitive ability and total cortical volume and cortical surface area, but not with mean cortical thickness. Mediation models indicated that the well-replicated height-general cognitive ability association is accounted for by individual differences in total cortical volume and cortical surface area (highly heritable metrics related to global brain size), and that the genetic association between cortical surface area and general cognitive ability underlies the phenotypic height-general cognitive ability relationship.
This is a preview of subscription content, log in via an institution to check access.
References
Adair LS, Fall CH, Osmond C, Stein AD, Martorell R, Ramirez-Zea M, Sachdev HS, Dahly DL, Bas I, Norris SA et al (2013) Associations of linear growth and relative weight gain during early life with adult health and human capital in countries of low and middle income: findings from five birth cohort studies. Lancet 382:525–534. https://doi.org/10.1016/S0140-6736(13)60103-8
Adams HH, Hibar DP, Chouraki V, Stein JL, Nyquist PA, Renteria ME, Trompet S, Arias-Vasquez A, Seshadri S, Desrivieres S et al (2016) Novel genetic loci underlying human intracranial volume identified through genome-wide association. Nat Neurosci 19:1569–1582. https://doi.org/10.1038/nn.4398
Andreasen NC, Flaum M, Swayze V 2nd, O’Leary DS, Alliger R, Cohen G, Ehrhardt J, Yuh WT (1993) Intelligence and brain structure in normal individuals. Am J Psychiatry 150:130–134. https://doi.org/10.1176/ajp.150.1.130
Brouwer RM, van Soelen IL, Swagerman SC, Schnack HG, Ehli EA, Kahn RS, Hulshoff Pol HE, Boomsma DI (2014) Genetic associations between intelligence and cortical thickness emerge at the start of puberty. Hum Brain Mapp 35:3760–3773. https://doi.org/10.1002/hbm.22435
Butler AA, Le Roith D (2001) Control of growth by the somatropic axis: growth hormone and the insulin-like growth factors have related and independent roles. Annu Rev Physiol 63:141–164. https://doi.org/10.1146/annurev.physiol.63.1.141
Cox SR, Bastin ME, Ritchie SJ, Dickie DA, Liewald DC, Munoz Maniega S, Redmond P, Royle NA, Pattie A, Valdes Hernandez M et al (2018) Brain cortical characteristics of lifetime cognitive ageing. Brain Struct Funct 223:509–518. https://doi.org/10.1007/s00429-017-1505-0
D’Ercole AJ, Ye P, Calikoglu AS, Gutierrez-Ospina G (1996) The role of the insulin-like growth factors in the central nervous system. Mol Neurobiol 13:227–255. https://doi.org/10.1007/BF02740625
Dale AM, Sereno MI (1993) Improved localizadon of cortical activity by combining EEG and MEG with MRI cortical surface reconstruction: a linear approach. J Cogn Neurosci 5:162–176. https://doi.org/10.1162/jocn.1993.5.2.162
Dale AM, Fischl B, Sereno MI (1999) Cortical surface-based analysis. I. Segmentation and surface reconstruction. Neuroimage 9:179–194. https://doi.org/10.1006/nimg.1998.0395
Ducharme S, Albaugh MD, Nguyen TV, Hudziak JJ, Mateos-Perez JM, Labbe A, Evans AC, Karama S, Brain Development Cooperative Group (2016) Trajectories of cortical thickness maturation in normal brain development—the importance of quality control procedures. Neuroimage 125:267–279. https://doi.org/10.1016/j.neuroimage.2015.10.010
Eyler LT, Chen CH, Panizzon MS, Fennema-Notestine C, Neale MC, Jak A, Jernigan TL, Fischl B, Franz CE, Lyons MJ et al (2012) A comparison of heritability maps of cortical surface area and thickness and the influence of adjustment for whole brain measures: a magnetic resonance imaging twin study. Twin Res Hum Genet 15:304–314. https://doi.org/10.1017/thg.2012.3
Fischl B, Dale AM (2000) Measuring the thickness of the human cerebral cortex from magnetic resonance images. Proc Natl Acad Sci USA 97:11050–11055. https://doi.org/10.1073/pnas.200033797
Fischl B, Sereno MI, Dale AM (1999) Cortical surface-based analysis. II: Inflation, flattening, and a surface-based coordinate system. Neuroimage 9:195–207. https://doi.org/10.1006/nimg.1998.0396
Fischl B, Salat DH, Busa E, Albert M, Dieterich M, Haselgrove C, van der Kouwe A, Killiany R, Kennedy D, Klaveness S et al (2002) Whole brain segmentation: automated labeling of neuroanatomical structures in the human brain. Neuron 33:341–355. https://doi.org/10.1016/S0896-6273(02)00569-X
Fischl B, Salat DH, van der Kouwe AJ, Makris N, Segonne F, Quinn BT, Dale AM (2004a) Sequence-independent segmentation of magnetic resonance images. Neuroimage 23 (Suppl 1):S69–S84. https://doi.org/10.1016/j.neuroimage.2004.07.016
Fischl B, van der Kouwe A, Destrieux C, Halgren E, Segonne F, Salat DH, Busa E, Seidman LJ, Goldstein J, Kennedy D et al (2004b) Automatically parcellating the human cerebral cortex. Cereb Cortex 14:11–22. https://doi.org/10.1093/cercor/bhg087
Fjell AM, Grydeland H, Krogsrud SK, Amlien I, Rohani DA, Ferschmann L, Storsve AB, Tamnes CK, Sala-Llonch R, Due-Tonnessen P et al (2015) Development and aging of cortical thickness correspond to genetic organization patterns. Proc Natl Acad Sci USA 112:15462–15467. https://doi.org/10.1073/pnas.1508831112
Forde NJ, Ronan L, Zwiers MP, Schweren LJS, Alexander-Bloch AF, Franke B, Faraone SV, Oosterlaan J, Heslenfeld DJ, Hartman CA et al (2017) Healthy cortical development through adolescence and early adulthood. Brain Struct Funct 222:3653–3663. https://doi.org/10.1007/s00429-017-1424-0
Gunnell D, Miller LL, Rogers I, Holly JM, ALSPAC Study Team (2005) Association of insulin-like growth factor I and insulin-like growth factor-binding protein-3 with intelligence quotient among 8- to 9-year-old children in the avon longitudinal study of parents and children. Pediatrics 116:e681–e686
Harris MA, Brett CE, Deary IJ, Starr JM (2016) Associations among height, body mass index and intelligence from age 11 to age 78 years. BMC Geriatr 16:167. https://doi.org/10.1186/s12877-016-0340-0
Humphreys LG, Davey TC, Park RK (1985) Longitudinal correlation analysis of standing height and intelligence. Child Dev 56:1465–1478
Keller MC, Garver-Apgar CE, Wright MJ, Martin NG, Corley RP, Stallings MC, Hewitt JK, Zietsch BP (2013) The genetic correlation between height and IQ: shared genes or assortative mating? PLoS Genet 9:e1003451. https://doi.org/10.1371/journal.pgen.1003451
Kremen WS, Thompson-Brenner H, Leung YM, Grant MD, Franz CE, Eisen SA, Jacobson KC, Boake C, Lyons MJ (2006) Genes, environment, and time: the Vietnam Era Twin Study of Aging (VETSA). Twin Res Hum Genet 9:1009–1022. https://doi.org/10.1375/183242706779462750
Kremen WS, Prom-Wormley E, Panizzon MS, Eyler LT, Fischl B, Neale MC, Franz CE, Lyons MJ, Pacheco J, Perry ME et al (2010) Genetic and environmental influences on the size of specific brain regions in midlife: the VETSA MRI study. Neuroimage 49:1213–1223. https://doi.org/10.1016/j.neuroimage.2009.09.043
Kremen WS, Franz CE, Lyons MJ (2013) VETSA: the Vietnam Era Twin Study of Aging. Twin Res Hum Genet 16:399–402. https://doi.org/10.1017/thg.2012.86
Li G, Nie J, Wang L, Shi F, Lin W, Gilmore JH, Shen D (2013) Mapping region-specific longitudinal cortical surface expansion from birth to 2 years of age. Cereb Cortex 23:2724–2733. https://doi.org/10.1093/cercor/bhs265
Lundgren EM, Cnattingius S, Jonsson B, Tuvemo T (2001) Intellectual and psychological performance in males born small for gestational age with and without catch-up growth. Pediatr Res 50:91–96. https://doi.org/10.1203/00006450-200107000-00017
Lundgren EM, Tuvemo T, Gustafsson J (2011) Short adult stature and overweight are associated with poor intellectual performance in subjects born preterm. Horm Res Paediatr 75:138–145. https://doi.org/10.1159/000322015
Lyall AE, Shi F, Geng X, Woolson S, Li G, Wang L, Hamer RM, Shen D, Gilmore JH (2015) Dynamic development of regional cortical thickness and surface area in early childhood. Cereb Cortex 25:2204–2212. https://doi.org/10.1093/cercor/bhu027
Lyons MJ, York TP, Franz CE, Grant MD, Eaves LJ, Jacobson KC, Schaie KW, Panizzon MS, Boake C, Xian H et al (2009) Genes determine stability and the environment determines change in cognitive ability during 35 years of adulthood. Psychol Sci 20:1146–1152. https://doi.org/10.1111/j.1467-9280.2009.02425.x
Lyons MJ, Panizzon MS, Liu W, McKenzie R, Bluestone NJ, Grant MD, Franz CE, Vuoksimaa EP, Toomey R, Jacobson KC et al (2017) A longitudinal twin study of general cognitive ability over four decades. Dev Psychol 53:1170–1177. https://doi.org/10.1037/dev0000303
Marioni RE, Batty GD, Hayward C, Kerr SM, Campbell A, Hocking LJ, Generation Scotland, Porteous DJ, Visscher PM, Deary IJ (2014) Common genetic variants explain the majority of the correlation between height and intelligence: the generation Scotland study. Behav Genet 44:91–96. https://doi.org/10.1007/s10519-014-9644-z
Narducci R, Baroncelli L, Sansevero G, Begenisic T, Prontera C, Sale A, Cenni MC, Berardi N, Maffei L (2018) Early impoverished environment delays the maturation of cerebral cortex. Sci Rep 8:1187. https://doi.org/10.1038/s41598-018-19459-y
NCD Risk Factor Collaboration (NCD-RisC) (2016) A century of trends in adult human height. Elife. https://doi.org/10.7554/eLife.13410
Neale MC, Cardon LR (1992) Methodology for genetic studies of twins and families. Kluwer, Dordrecht
Panizzon MS, Fennema-Notestine C, Eyler LT, Jernigan TL, Prom-Wormley E, Neale M, Jacobson K, Lyons MJ, Grant MD, Franz CE et al (2009) Distinct genetic influences on cortical surface area and cortical thickness. Cereb Cortex 19:2728–2735. https://doi.org/10.1093/cercor/bhp026
Pietschnig J, Penke L, Wicherts JM, Zeiler M, Voracek M (2015) Meta-analysis of associations between human brain volume and intelligence differences: how strong are they and what do they mean? Neurosci Biobehav Rev 57:411–432. https://doi.org/10.1016/j.neubiorev.2015.09.017
Posthuma D, de Geus EJ, Neale MC, Hulshoff Pol HE, Baare WEC, Kahn RS, Boomsma D (2000) Multivariate genetic analysis of brain structure in an extended twin design. Behav Genet 30:311–319
Posthuma D, De Geus EJ, Baare WF, Hulshoff Pol HE, Kahn RS, Boomsma DI (2002) The association between brain volume and intelligence is of genetic origin. Nat Neurosci 5:83–84. https://doi.org/10.1038/nn0202-83
Raznahan A, Greenstein D, Lee NR, Clasen LS, Giedd JN (2012) Prenatal growth in humans and postnatal brain maturation into late adolescence. Proc Natl Acad Sci USA 109:11366–11371. https://doi.org/10.1073/pnas.1203350109
Remer J, Croteau-Chonka E, Dean DC 3rd, D’Arpino S, Dirks H, Whiley D, Deoni SCL (2017) Quantifying cortical development in typically developing toddlers and young children, 1–6 years of age. Neuroimage 153:246–261. https://doi.org/10.1016/j.neuroimage.2017.04.010
Ritchie SJ, Dickie DA, Cox SR, Valdes Hernandez MDC, Sibbett R, Pattie A, Anblagan D, Redmond P, Royle NA, Corley J et al (2018) Brain structural differences between 73- and 92-year olds matched for childhood intelligence, social background, and intracranial volume. Neurobiol Aging 62:146–158. https://doi.org/10.1016/j.neurobiolaging.2017.10.005
Russ TC, Kivimaki M, Starr JM, Stamatakis E, Batty GD (2014) Height in relation to dementia death: individual participant meta-analysis of 18 UK prospective cohort studies. Br J Psychiatry 205:348–354. https://doi.org/10.1192/bjp.bp.113.142984
Sammallahti S, Pyhala R, Lahti M, Lahti J, Pesonen AK, Heinonen K, Hovi P, Eriksson JG, Strang-Karlsson S, Andersson S et al (2014) Infant growth after preterm birth and neurocognitive abilities in young adulthood. J Pediatr 165:1109–1115.e3. https://doi.org/10.1016/j.jpeds.2014.08.028
Silventoinen K, Posthuma D, van Beijsterveldt T, Bartels M, Boomsma DI (2006) Genetic contributions to the association between height and intelligence: evidence from Dutch twin data from childhood to middle age. Genes Brain Behav 5:585–595. https://doi.org/10.1111/j.1601-183X.2006.00208.x
Silventoinen K, Iacono WG, Krueger R, McGue M (2012) Genetic and environmental contributions to the association between anthropometric measures and IQ: a study of Minnesota twins at age 11 and 17. Behav Genet 42:393–401. https://doi.org/10.1007/s10519-011-9521-y
Solsnes AE, Grunewaldt KH, Bjuland KJ, Stavnes EM, Bastholm IA, Aanes S, Ostgard HF, Haberg A, Lohaugen GC, Skranes J et al (2015) Cortical morphometry and IQ in VLBW children without cerebral palsy born in 2003–2007. Neuroimage Clin 8:193–201. https://doi.org/10.1016/j.nicl.2015.04.004
Storsve AB, Fjell AM, Tamnes CK, Westlye LT, Overbye K, Aasland HW, Walhovd KB (2014) Differential longitudinal changes in cortical thickness, surface area and volume across the adult life span: regions of accelerating and decelerating change. J Neurosci 34:8488–8498. https://doi.org/10.1523/JNEUROSCI.0391-14.2014
Taki Y, Hashizume H, Sassa Y, Takeuchi H, Asano M, Asano K, Kotozaki Y, Nouchi R, Wu K, Fukuda H et al (2012) Correlation among body height, intelligence, and brain gray matter volume in healthy children. Neuroimage 59:1023–1027. https://doi.org/10.1016/j.neuroimage.2011.08.092
Tamnes CK, Fjell AM, Ostby Y, Westlye LT, Due-Tonnessen P, Bjornerud A, Walhovd KB (2011) The brain dynamics of intellectual development: waxing and waning white and gray matter. Neuropsychologia 49:3605–3611. https://doi.org/10.1016/j.neuropsychologia.2011.09.012
Vuoksimaa E, Panizzon MS, Chen CH, Fiecas M, Eyler LT, Fennema-Notestine C, Hagler DJ, Fischl B, Franz CE, Jak A et al (2015) The genetic association between neocortical volume and general cognitive ability is driven by global surface area rather than thickness. Cereb Cortex 25:2127–2137. https://doi.org/10.1093/cercor/bhu018
Vuoksimaa E, Panizzon MS, Chen CH, Fiecas M, Eyler LT, Fennema-Notestine C, Hagler DJ Jr, Franz CE, Jak AJ, Lyons MJ et al (2016) Is bigger always better? The importance of cortical configuration with respect to cognitive ability. Neuroimage 129:356–366. https://doi.org/10.1016/j.neuroimage.2016.01.049
Walhovd KB, Fjell AM, Reinvang I, Lundervold A, Dale AM, Eilertsen DE, Quinn BT, Salat D, Makris N, Fischl B (2005) Effects of age on volumes of cortex, white matter and subcortical structures. Neurobiol Aging 26:1261–1270. https://doi.org/10.1016/j.neurobiolaging.2005.05.020
Walhovd KB, Krogsrud SK, Amlien IK, Bartsch H, Bjornerud A, Due-Tonnessen P, Grydeland H, Hagler DJ Jr, Haberg AK, Kremen WS et al (2016) Neurodevelopmental origins of lifespan changes in brain and cognition. Proc Natl Acad Sci USA 113:9357–9362. https://doi.org/10.1073/pnas.1524259113
Walhovd KB, Fjell AM, Giedd J, Dale AM, Brown TT (2017) Through thick and thin: a need to reconcile contradictory results on trajectories in human cortical development. Cereb Cortex 27:1472–1481. https://doi.org/10.1093/cercor/bhv301
Winkler AM, Kochunov P, Blangero J, Almasy L, Zilles K, Fox PT, Duggirala R, Glahn DC (2010) Cortical thickness or grey matter volume? The importance of selecting the phenotype for imaging genetics studies. Neuroimage 53:1135–1146. https://doi.org/10.1016/j.neuroimage.2009.12.028
Acknowledgements
We would like to acknowledge the continued cooperation and participation of the members of the VET Registry and their families.
Funding
Supported by NIA R01 AG022381, AG050595 and R03 AG 046413, and, in part, with resources of the VA San Diego Center of Excellence for Stress and Mental Health. The content of this manuscript is the responsibility of the authors and does not represent official views of NIA/NIH, or the VA. The Cooperative Studies Program of the U.S. Department of Veterans Affairs provided financial support for development and maintenance of the Vietnam Era Twin Registry.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
AMD is a founder of and holds equity in CorTechs Laboratories, Inc., and also serves on its Scientific Advisory Board. He is a member of the Scientific Advisory Board of Human Longevity, Inc., and receives funding through research agreements with General Electric Healthcare and Medtronic, Inc. The terms of these arrangements have been reviewed and approved by the University of California, San Diego, in accordance with its conflict of interest policies. All other authors have no conflicts of interest to declare.
Electronic supplementary material
Below is the link to the electronic supplementary material.
Rights and permissions
About this article
Cite this article
Vuoksimaa, E., Panizzon, M.S., Franz, C.E. et al. Brain structure mediates the association between height and cognitive ability. Brain Struct Funct 223, 3487–3494 (2018). https://doi.org/10.1007/s00429-018-1675-4
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00429-018-1675-4