TY - JOUR
T1 - Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa
AU - Walton, E.
AU - Hibar, D.
AU - Yilmaz, Z.
AU - Jahanshad, N.
AU - Cheung, J.
AU - Batury, V. -L.
AU - Seitz, J.
AU - Bulik, C. M.
AU - Thompson, P. M.
AU - Ehrlich, Stefan
AU - Hibar, Derrek P.
AU - Stein, Jason L.
AU - Renteria, Miguel E.
AU - Arias-Vasquez, Alejandro
AU - Desrivieres, Sylvane
AU - Jahanshad, Neda
AU - Toro, Roberto
AU - Wittfeld, Katharina
AU - Abramovic, Lucija
AU - Andersson, Micael
AU - Aribisala, Benjamin S.
AU - Armstrong, Nicola J.
AU - Bernard, Manon
AU - Bohlken, Marc M.
AU - Boks, Marco P.
AU - Bralten, Janita
AU - Brown, Andrew A.
AU - Chakravarty, M. Mallar
AU - Chen, Qiang
AU - Ching, Christopher R. K.
AU - Cuellar-Partida, Gabriel
AU - Den Braber, Anouk
AU - Giddaluru, Sudheer
AU - Goldman, Aaron L.
AU - Grimm, Oliver
AU - Guadalupe, Tulio
AU - Hass, Johanna
AU - Woldehawariat, Girma
AU - Klein, Marieke
AU - van Eijk, Kristel R.
AU - Cahn, Wiepke
AU - Kahn, Rene S.
AU - van Haren, Neeltje E. M.
AU - Brouwer, Rachel M.
AU - Pol, Hilleke E. Hulshoff
AU - Ophoff, Roel
AU - Adan, Roger
AU - Kas, Martien
AU - Koeleman, Bobby
AU - Ophoff, Roel
N1 - Funding Information:
This work was funded through the Collaborative research center grant (DFG, SFB 940/2) and Schweizer Anorexia Nervosa Stiftung (both to SE), the National Institutes of Health K01MH109782 (ZY), NIH Big Data to Knowledge Initiative U54EB020403 and the Kavli Foundation (both to PT). CB acknowledges funding from the Swedish Research Council (VR Dnr: 538-2013-8864). Acknowledgements ENIGMA Genetics Working Group Eating Disorders Working Group of the Psychiatric Genomics Consortium
Publisher Copyright:
© 2018, The Author(s).
PY - 2019/7/1
Y1 - 2019/7/1
N2 - In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (p
FDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (p
FDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN.
AB - In MRI scans of patients with anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknown whether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlying AN. Here, we used a battery of methods (LD score regression, genetic risk scores, sign test, SNP effect concordance analysis, and Mendelian randomization) to investigate the genetic covariation between subcortical brain volumes and risk for AN based on summary measures retrieved from genome-wide association studies of regional brain volumes (ENIGMA consortium, n = 13,170) and genetic risk for AN (PGC-ED consortium, n = 14,477). Genetic correlations ranged from − 0.10 to 0.23 (all p > 0.05). There were some signs of an inverse concordance between greater thalamus volume and risk for AN (permuted p = 0.009, 95% CI: [0.005, 0.017]). A genetic variant in the vicinity of ZW10, a gene involved in cell division, and neurotransmitter and immune system relevant genes, in particular DRD2, was significantly associated with AN only after conditioning on its association with caudate volume (p
FDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (p
FDR = 0.021). In this comprehensive set of analyses and based on the largest available sample sizes to date, there was weak evidence for associations between risk for AN and risk for abnormal subcortical brain volumes at a global level (that is, common variant genetic architecture), but suggestive evidence for effects of single genetic markers. Highly powered multimodal brain- and disorder-related genome-wide studies are needed to further dissect the shared genetic influences on brain structure and risk for AN.
KW - Anorexia nervosa
KW - Brain structure
KW - Genetic correlation
UR - http://www.scopus.com/inward/record.url?scp=85058029396&partnerID=8YFLogxK
U2 - 10.1007/s12035-018-1439-4
DO - 10.1007/s12035-018-1439-4
M3 - Article
C2 - 30519816
SN - 0893-7648
VL - 56
SP - 5146
EP - 5156
JO - Molecular Neurobiology
JF - Molecular Neurobiology
IS - 7
ER -