Identification of common variants associated with human hippocampal and intracranial volumes

JL Stein; SE Medland; AA Vasquez; DP Hibar; RE Senstad; AM Winkler; R Toro; K Appel; R Bartecek; O Bergmann; M (Manon) Bernard; AA Brown; DM Cannon; MM Chakravarty; A Christoforou; M Domin; O Grimm; M Hollinshead; AJ Holmes; G Homuth; JJ (Jouke Jan) Hottenga; C Langan; LM Lopez; NK Hansell; KS Hwang; S Kim; G Laje; PH Lee; XM Liu; E Loth; A Lourdusamy; M Mattingsdal; S Mohnke; SM Maniega; K Nho; AC Nugent; C O'Brien; M Papmeyer; B Putz; A Ramasamy; J Rasmussen; Marrijan Rijpkema; SL Risacher; JC Roddey; EJ Rose; M Ryten; Lucy Shen; E Sprooten; E Strengman; A Teumer; D Trabzuni; J Turner; K van Eijk; TGM van Erp; MJ van Tol; K Wittfeld; C Wolf; S Woudstra; A Aleman; S Alhusaini; L Almasy; EB Binder; DG Brohawn; RM Cantor; MA Carless; A Corvin; M Czisch; JE Curran; G Davies; MAA de Almeida; N Delanty; C Depondt; R Duggirala; TD Dyer; S Erk; J Fagerness; PT Fox; NB Freimer; M Gill; HHH Goring; DJ Hagler; D Hoehn; F Holsboer; M Hoogman; N Hosten; N Jahanshad; MP Johnson; D Kasperaviciute; JW Kent; P Kochunov; JL Lancaster; SM Lawrie; DC Liewald; R Mandl; M Matarin; M Mattheisen; E Meisenzahl; I Melle; EK Moses; TW Muhleisen; M Nauck; MM Nothen; RL Olvera; M Pandolfo; GB Pike; R Puls; I Reinvang; ME Renteria; M Rietschel; JL Roffman; NA Royle; D Rujescu; J Savitz; HG Schnack; K Schnell; N Seiferth; C Smith; VM Steen; MCV Hernandez; Marieke Heuvel; NJ van der Wee; Neeltje van Haren; JA Veltman; H Volzke; R walker; LT Westlye; CD Whelan; I Agartz; DI Boomsma; GL Cavalleri; AM Dale; S Djurovic; WC Drevets; P Hagoort; J Hall; A Heinz; CR Jack; TM Foroud; S Le Hellard; F Macciardi; GW Montgomery; JB Poline; DJ Porteous; SM Sisodiya; JM Starr; J Sussmann; AW Toga; DJ Veltman; H Walter; MW Weiner; JC Bis; Arfan Ikram; AV Smith; V Gudnason; C Tzourio; Meike Vernooij; LJ (Lenore) Launer; C DeCarli; S Seshadri; OA Andreassen; LG Apostolova; ME Bastin; J Blangero; HG Brunner; RL Buckner; S Cichon; G Coppola; GI de Zubicaray; IJ Deary; G Donohoe; EJC de Geus; T Espeseth; G Fernandez; DC Glahn; HJ Grabe; J Hardy; HEH Pol; M Jenkinson; RS Kahn; C McDonald; AM McIntosh; FJ McMahon; KL McMahon; A Meyer-Lindenberg; DW Morris; B Muller-Myhsok; TE Nichols; RA Ophoff; T Paus; Z Pausova; BW Penninx; SG Potkin; PG Samann; AJ Saykin; G Schumann; JW Smoller; JM Wardlaw; ME Weale; NG Martin; B Franke; MJ Wright; PM Thompson

doi:10.1038/ng.2250

Identification of common variants associated with human hippocampal and intracranial volumes

JL Stein
, SE Medland
, AA Vasquez
, DP Hibar
, RE Senstad
, AM Winkler
, R Toro
, K Appel
, R Bartecek
, O Bergmann
, M (Manon) Bernard
, AA Brown
, DM Cannon
, MM Chakravarty
, A Christoforou
, M Domin
, O Grimm
, M Hollinshead
, AJ Holmes
, G Homuth

JJ (Jouke Jan) Hottenga, C Langan, LM Lopez, NK Hansell, KS Hwang, S Kim, G Laje, PH Lee, XM Liu, E Loth, A Lourdusamy, M Mattingsdal, S Mohnke, SM Maniega, K Nho, AC Nugent, C O'Brien, M Papmeyer, B Putz, A Ramasamy, J Rasmussen, Marrijan Rijpkema, SL Risacher, JC Roddey, EJ Rose, M Ryten, Lucy Shen, E Sprooten, E Strengman, A Teumer, D Trabzuni, J Turner, K van Eijk, TGM van Erp, MJ van Tol, K Wittfeld, C Wolf, S Woudstra, A Aleman, S Alhusaini, L Almasy, EB Binder, DG Brohawn, RM Cantor, MA Carless, A Corvin, M Czisch, JE Curran, G Davies, MAA de Almeida, N Delanty, C Depondt, R Duggirala, TD Dyer, S Erk, J Fagerness, PT Fox, NB Freimer, M Gill, HHH Goring, DJ Hagler, D Hoehn, F Holsboer, M Hoogman, N Hosten, N Jahanshad, MP Johnson, D Kasperaviciute, JW Kent, P Kochunov, JL Lancaster, SM Lawrie, DC Liewald, R Mandl, M Matarin, M Mattheisen, E Meisenzahl, I Melle, EK Moses, TW Muhleisen, M Nauck, MM Nothen, RL Olvera, M Pandolfo, GB Pike, R Puls, I Reinvang, ME Renteria, M Rietschel, JL Roffman, NA Royle, D Rujescu, J Savitz, HG Schnack, K Schnell, N Seiferth, C Smith, VM Steen, MCV Hernandez, Marieke Heuvel, NJ van der Wee, Neeltje van Haren, JA Veltman, H Volzke, R walker, LT Westlye, CD Whelan, I Agartz, DI Boomsma, GL Cavalleri, AM Dale, S Djurovic, WC Drevets, P Hagoort, J Hall, A Heinz, CR Jack, TM Foroud, S Le Hellard, F Macciardi, GW Montgomery, JB Poline, DJ Porteous, SM Sisodiya, JM Starr, J Sussmann, AW Toga, DJ Veltman, H Walter, MW Weiner, JC Bis, Arfan Ikram, AV Smith, V Gudnason, C Tzourio, Meike Vernooij, LJ (Lenore) Launer, C DeCarli, S Seshadri, OA Andreassen, LG Apostolova, ME Bastin, J Blangero, HG Brunner, RL Buckner, S Cichon, G Coppola, GI de Zubicaray, IJ Deary, G Donohoe, EJC de Geus, T Espeseth, G Fernandez, DC Glahn, HJ Grabe, J Hardy, HEH Pol, M Jenkinson, RS Kahn, C McDonald, AM McIntosh, FJ McMahon, KL McMahon, A Meyer-Lindenberg, DW Morris, B Muller-Myhsok, TE Nichols, RA Ophoff, T Paus, Z Pausova, BW Penninx, SG Potkin, PG Samann, AJ Saykin, G Schumann, JW Smoller, JM Wardlaw, ME Weale, NG Martin, B Franke, MJ Wright, PM Thompson

External organisation

Research output: Contribution to journal › Article › Academic › peer-review

542 Citations (Scopus)

Abstract

Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease(1,2) and is reduced in schizophrenia(3), major depression(4) and mesial temporal lobe epilepsy(5). Whereas many brain imaging phenotypes are highly heritable(6,7), identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)).

Original language	Undefined/Unknown
Pages (from-to)	552-561
Number of pages	10
Journal	Nature Genetics
Volume	44
Issue number	5
DOIs	https://doi.org/10.1038/ng.2250
Publication status	Published - 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Research programs

EMC NIHES-01-64-01
EMC NIHES-01-64-02
EMC NIHES-03-30-01

Access to Document

10.1038/ng.2250

http://hdl.handle.net/1765/57534

Cite this

Stein, JL., Medland, SE., Vasquez, AA., Hibar, DP., Senstad, RE., Winkler, AM., Toro, R., Appel, K., Bartecek, R., Bergmann, O., Bernard, M., Brown, AA., Cannon, DM., Chakravarty, MM., Christoforou, A., Domin, M., Grimm, O., Hollinshead, M., Holmes, AJ., ... Thompson, PM. (2012). Identification of common variants associated with human hippocampal and intracranial volumes. Nature Genetics, 44(5), 552-561. https://doi.org/10.1038/ng.2250

@article{1843131f5bb8489dbb5089cfbe37dac7,

title = "Identification of common variants associated with human hippocampal and intracranial volumes",

abstract = "Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease(1,2) and is reduced in schizophrenia(3), major depression(4) and mesial temporal lobe epilepsy(5). Whereas many brain imaging phenotypes are highly heritable(6,7), identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)).",

author = "JL Stein and SE Medland and AA Vasquez and DP Hibar and RE Senstad and AM Winkler and R Toro and K Appel and R Bartecek and O Bergmann and Bernard, \{M (Manon)\} and AA Brown and DM Cannon and MM Chakravarty and A Christoforou and M Domin and O Grimm and M Hollinshead and AJ Holmes and G Homuth and Hottenga, \{JJ (Jouke Jan)\} and C Langan and LM Lopez and NK Hansell and KS Hwang and S Kim and G Laje and PH Lee and XM Liu and E Loth and A Lourdusamy and M Mattingsdal and S Mohnke and SM Maniega and K Nho and AC Nugent and C O'Brien and M Papmeyer and B Putz and A Ramasamy and J Rasmussen and Marrijan Rijpkema and SL Risacher and JC Roddey and EJ Rose and M Ryten and Lucy Shen and E Sprooten and E Strengman and A Teumer and D Trabzuni and J Turner and \{van Eijk\}, K and \{van Erp\}, TGM and \{van Tol\}, MJ and K Wittfeld and C Wolf and S Woudstra and A Aleman and S Alhusaini and L Almasy and EB Binder and DG Brohawn and RM Cantor and MA Carless and A Corvin and M Czisch and JE Curran and G Davies and \{de Almeida\}, MAA and N Delanty and C Depondt and R Duggirala and TD Dyer and S Erk and J Fagerness and PT Fox and NB Freimer and M Gill and HHH Goring and DJ Hagler and D Hoehn and F Holsboer and M Hoogman and N Hosten and N Jahanshad and MP Johnson and D Kasperaviciute and JW Kent and P Kochunov and JL Lancaster and SM Lawrie and DC Liewald and R Mandl and M Matarin and M Mattheisen and E Meisenzahl and I Melle and EK Moses and TW Muhleisen and M Nauck and MM Nothen and RL Olvera and M Pandolfo and GB Pike and R Puls and I Reinvang and ME Renteria and M Rietschel and JL Roffman and NA Royle and D Rujescu and J Savitz and HG Schnack and K Schnell and N Seiferth and C Smith and VM Steen and MCV Hernandez and Marieke Heuvel and \{van der Wee\}, NJ and \{van Haren\}, Neeltje and JA Veltman and H Volzke and R walker and LT Westlye and CD Whelan and I Agartz and DI Boomsma and GL Cavalleri and AM Dale and S Djurovic and WC Drevets and P Hagoort and J Hall and A Heinz and CR Jack and TM Foroud and \{Le Hellard\}, S and F Macciardi and GW Montgomery and JB Poline and DJ Porteous and SM Sisodiya and JM Starr and J Sussmann and AW Toga and DJ Veltman and H Walter and MW Weiner and JC Bis and Arfan Ikram and AV Smith and V Gudnason and C Tzourio and Meike Vernooij and Launer, \{LJ (Lenore)\} and C DeCarli and S Seshadri and OA Andreassen and LG Apostolova and ME Bastin and J Blangero and HG Brunner and RL Buckner and S Cichon and G Coppola and \{de Zubicaray\}, GI and IJ Deary and G Donohoe and \{de Geus\}, EJC and T Espeseth and G Fernandez and DC Glahn and HJ Grabe and J Hardy and HEH Pol and M Jenkinson and RS Kahn and C McDonald and AM McIntosh and FJ McMahon and KL McMahon and A Meyer-Lindenberg and DW Morris and B Muller-Myhsok and TE Nichols and RA Ophoff and T Paus and Z Pausova and BW Penninx and SG Potkin and PG Samann and AJ Saykin and G Schumann and JW Smoller and JM Wardlaw and ME Weale and NG Martin and B Franke and MJ Wright and PM Thompson",

year = "2012",

doi = "10.1038/ng.2250",

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volume = "44",

pages = "552--561",

journal = "Nature Genetics",

issn = "1061-4036",

publisher = "Nature Research",

number = "5",

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Stein, JL, Medland, SE, Vasquez, AA, Hibar, DP, Senstad, RE, Winkler, AM, Toro, R, Appel, K, Bartecek, R, Bergmann, O, Bernard, M, Brown, AA, Cannon, DM, Chakravarty, MM, Christoforou, A, Domin, M, Grimm, O, Hollinshead, M, Holmes, AJ, Homuth, G, Hottenga, JJ, Langan, C, Lopez, LM, Hansell, NK, Hwang, KS, Kim, S, Laje, G, Lee, PH, Liu, XM, Loth, E, Lourdusamy, A, Mattingsdal, M, Mohnke, S, Maniega, SM, Nho, K, Nugent, AC, O'Brien, C, Papmeyer, M, Putz, B, Ramasamy, A, Rasmussen, J, Rijpkema, M, Risacher, SL, Roddey, JC, Rose, EJ, Ryten, M, Shen, L, Sprooten, E, Strengman, E, Teumer, A, Trabzuni, D, Turner, J, van Eijk, K, van Erp, TGM, van Tol, MJ, Wittfeld, K, Wolf, C, Woudstra, S, Aleman, A, Alhusaini, S, Almasy, L, Binder, EB, Brohawn, DG, Cantor, RM, Carless, MA, Corvin, A, Czisch, M, Curran, JE, Davies, G, de Almeida, MAA, Delanty, N, Depondt, C, Duggirala, R, Dyer, TD, Erk, S, Fagerness, J, Fox, PT, Freimer, NB, Gill, M, Goring, HHH, Hagler, DJ, Hoehn, D, Holsboer, F, Hoogman, M, Hosten, N, Jahanshad, N, Johnson, MP, Kasperaviciute, D, Kent, JW, Kochunov, P, Lancaster, JL, Lawrie, SM, Liewald, DC, Mandl, R, Matarin, M, Mattheisen, M, Meisenzahl, E, Melle, I, Moses, EK, Muhleisen, TW, Nauck, M, Nothen, MM, Olvera, RL, Pandolfo, M, Pike, GB, Puls, R, Reinvang, I, Renteria, ME, Rietschel, M, Roffman, JL, Royle, NA, Rujescu, D, Savitz, J, Schnack, HG, Schnell, K, Seiferth, N, Smith, C, Steen, VM, Hernandez, MCV, Heuvel, M, van der Wee, NJ, van Haren, N, Veltman, JA, Volzke, H, walker, R, Westlye, LT, Whelan, CD, Agartz, I, Boomsma, DI, Cavalleri, GL, Dale, AM, Djurovic, S, Drevets, WC, Hagoort, P, Hall, J, Heinz, A, Jack, CR, Foroud, TM, Le Hellard, S, Macciardi, F, Montgomery, GW, Poline, JB, Porteous, DJ, Sisodiya, SM, Starr, JM, Sussmann, J, Toga, AW, Veltman, DJ, Walter, H, Weiner, MW, Bis, JC, Ikram, A, Smith, AV, Gudnason, V, Tzourio, C, Vernooij, M, Launer, LJ, DeCarli, C, Seshadri, S, Andreassen, OA, Apostolova, LG, Bastin, ME, Blangero, J, Brunner, HG, Buckner, RL, Cichon, S, Coppola, G, de Zubicaray, GI, Deary, IJ, Donohoe, G, de Geus, EJC, Espeseth, T, Fernandez, G, Glahn, DC, Grabe, HJ, Hardy, J, Pol, HEH, Jenkinson, M, Kahn, RS, McDonald, C, McIntosh, AM, McMahon, FJ, McMahon, KL, Meyer-Lindenberg, A, Morris, DW, Muller-Myhsok, B, Nichols, TE, Ophoff, RA, Paus, T, Pausova, Z, Penninx, BW, Potkin, SG, Samann, PG, Saykin, AJ, Schumann, G, Smoller, JW, Wardlaw, JM, Weale, ME, Martin, NG, Franke, B, Wright, MJ & Thompson, PM 2012, 'Identification of common variants associated with human hippocampal and intracranial volumes', Nature Genetics, vol. 44, no. 5, pp. 552-561. https://doi.org/10.1038/ng.2250

TY - JOUR

T1 - Identification of common variants associated with human hippocampal and intracranial volumes

AU - Stein, JL

AU - Medland, SE

AU - Vasquez, AA

AU - Hibar, DP

AU - Senstad, RE

AU - Winkler, AM

AU - Toro, R

AU - Appel, K

AU - Bartecek, R

AU - Bergmann, O

AU - Bernard, M (Manon)

AU - Brown, AA

AU - Cannon, DM

AU - Chakravarty, MM

AU - Christoforou, A

AU - Domin, M

AU - Grimm, O

AU - Hollinshead, M

AU - Holmes, AJ

AU - Homuth, G

AU - Hottenga, JJ (Jouke Jan)

AU - Langan, C

AU - Lopez, LM

AU - Hansell, NK

AU - Hwang, KS

AU - Kim, S

AU - Laje, G

AU - Lee, PH

AU - Liu, XM

AU - Loth, E

AU - Lourdusamy, A

AU - Mattingsdal, M

AU - Mohnke, S

AU - Maniega, SM

AU - Nho, K

AU - Nugent, AC

AU - O'Brien, C

AU - Papmeyer, M

AU - Putz, B

AU - Ramasamy, A

AU - Rasmussen, J

AU - Rijpkema, Marrijan

AU - Risacher, SL

AU - Roddey, JC

AU - Rose, EJ

AU - Ryten, M

AU - Shen, Lucy

AU - Sprooten, E

AU - Strengman, E

AU - Teumer, A

AU - Trabzuni, D

AU - Turner, J

AU - van Eijk, K

AU - van Erp, TGM

AU - van Tol, MJ

AU - Wittfeld, K

AU - Wolf, C

AU - Woudstra, S

AU - Aleman, A

AU - Alhusaini, S

AU - Almasy, L

AU - Binder, EB

AU - Brohawn, DG

AU - Cantor, RM

AU - Carless, MA

AU - Corvin, A

AU - Czisch, M

AU - Curran, JE

AU - Davies, G

AU - de Almeida, MAA

AU - Delanty, N

AU - Depondt, C

AU - Duggirala, R

AU - Dyer, TD

AU - Erk, S

AU - Fagerness, J

AU - Fox, PT

AU - Freimer, NB

AU - Gill, M

AU - Goring, HHH

AU - Hagler, DJ

AU - Hoehn, D

AU - Holsboer, F

AU - Hoogman, M

AU - Hosten, N

AU - Jahanshad, N

AU - Johnson, MP

AU - Kasperaviciute, D

AU - Kent, JW

AU - Kochunov, P

AU - Lancaster, JL

AU - Lawrie, SM

AU - Liewald, DC

AU - Mandl, R

AU - Matarin, M

AU - Mattheisen, M

AU - Meisenzahl, E

AU - Melle, I

AU - Moses, EK

AU - Muhleisen, TW

AU - Nauck, M

AU - Nothen, MM

AU - Olvera, RL

AU - Pandolfo, M

AU - Pike, GB

AU - Puls, R

AU - Reinvang, I

AU - Renteria, ME

AU - Rietschel, M

AU - Roffman, JL

AU - Royle, NA

AU - Rujescu, D

AU - Savitz, J

AU - Schnack, HG

AU - Schnell, K

AU - Seiferth, N

AU - Smith, C

AU - Steen, VM

AU - Hernandez, MCV

AU - Heuvel, Marieke

AU - van der Wee, NJ

AU - van Haren, Neeltje

AU - Veltman, JA

AU - Volzke, H

AU - walker, R

AU - Westlye, LT

AU - Whelan, CD

AU - Agartz, I

AU - Boomsma, DI

AU - Cavalleri, GL

AU - Dale, AM

AU - Djurovic, S

AU - Drevets, WC

AU - Hagoort, P

AU - Hall, J

AU - Heinz, A

AU - Jack, CR

AU - Foroud, TM

AU - Le Hellard, S

AU - Macciardi, F

AU - Montgomery, GW

AU - Poline, JB

AU - Porteous, DJ

AU - Sisodiya, SM

AU - Starr, JM

AU - Sussmann, J

AU - Toga, AW

AU - Veltman, DJ

AU - Walter, H

AU - Weiner, MW

AU - Bis, JC

AU - Ikram, Arfan

AU - Smith, AV

AU - Gudnason, V

AU - Tzourio, C

AU - Vernooij, Meike

AU - Launer, LJ (Lenore)

AU - DeCarli, C

AU - Seshadri, S

AU - Andreassen, OA

AU - Apostolova, LG

AU - Bastin, ME

AU - Blangero, J

AU - Brunner, HG

AU - Buckner, RL

AU - Cichon, S

AU - Coppola, G

AU - de Zubicaray, GI

AU - Deary, IJ

AU - Donohoe, G

AU - de Geus, EJC

AU - Espeseth, T

AU - Fernandez, G

AU - Glahn, DC

AU - Grabe, HJ

AU - Hardy, J

AU - Pol, HEH

AU - Jenkinson, M

AU - Kahn, RS

AU - McDonald, C

AU - McIntosh, AM

AU - McMahon, FJ

AU - McMahon, KL

AU - Meyer-Lindenberg, A

AU - Morris, DW

AU - Muller-Myhsok, B

AU - Nichols, TE

AU - Ophoff, RA

AU - Paus, T

AU - Pausova, Z

AU - Penninx, BW

AU - Potkin, SG

AU - Samann, PG

AU - Saykin, AJ

AU - Schumann, G

AU - Smoller, JW

AU - Wardlaw, JM

AU - Weale, ME

AU - Martin, NG

AU - Franke, B

AU - Wright, MJ

AU - Thompson, PM

PY - 2012

Y1 - 2012

N2 - Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease(1,2) and is reduced in schizophrenia(3), major depression(4) and mesial temporal lobe epilepsy(5). Whereas many brain imaging phenotypes are highly heritable(6,7), identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)).

AB - Identifying genetic variants influencing human brain structures may reveal new biological mechanisms underlying cognition and neuropsychiatric illness. The volume of the hippocampus is a biomarker of incipient Alzheimer's disease(1,2) and is reduced in schizophrenia(3), major depression(4) and mesial temporal lobe epilepsy(5). Whereas many brain imaging phenotypes are highly heritable(6,7), identifying and replicating genetic influences has been difficult, as small effects and the high costs of magnetic resonance imaging (MRI) have led to underpowered studies. Here we report genome-wide association meta-analyses and replication for mean bilateral hippocampal, total brain and intracranial volumes from a large multinational consortium. The intergenic variant rs7294919 was associated with hippocampal volume (12q24.22; N = 21,151; P = 6.70 x 10(-16)) and the expression levels of the positional candidate gene TESC in brain tissue. Additionally, rs10784502, located within HMGA2, was associated with intracranial volume (12q14.3; N = 15,782; P = 1.12 x 10(-12)). We also identified a suggestive association with total brain volume at rs10494373 within DDR2 (1q23.3; N = 6,500; P = 5.81 x 10(-7)).

U2 - 10.1038/ng.2250

DO - 10.1038/ng.2250

M3 - Article

C2 - 22504417

SN - 1061-4036

VL - 44

SP - 552

EP - 561

JO - Nature Genetics

JF - Nature Genetics

IS - 5

ER -