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Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa

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Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa. / Walton, E; Hibar, D; Yilmaz, Z; Jahanshad, N; Batury, V-L; Seitz, J; Bulik, C M; PGC-ED; Thompson, P M; Ehrlich, Stefan.

In: Molecular Neurobiology, Vol. 56, No. 7, 01.07.2019, p. 5146-5156.

Research output: Contribution to journalArticle

Harvard

Walton, E, Hibar, D, Yilmaz, Z, Jahanshad, N, Batury, V-L, Seitz, J, Bulik, CM, PGC-ED, Thompson, PM & Ehrlich, S 2019, 'Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa', Molecular Neurobiology, vol. 56, no. 7, pp. 5146-5156. https://doi.org/10.1007/s12035-018-1439-4

APA

Walton, E., Hibar, D., Yilmaz, Z., Jahanshad, N., Batury, V-L., Seitz, J., ... Ehrlich, S. (2019). Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa. Molecular Neurobiology, 56(7), 5146-5156. https://doi.org/10.1007/s12035-018-1439-4

Vancouver

Walton E, Hibar D, Yilmaz Z, Jahanshad N, Batury V-L, Seitz J et al. Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa. Molecular Neurobiology. 2019 Jul 1;56(7):5146-5156. https://doi.org/10.1007/s12035-018-1439-4

Author

Walton, E ; Hibar, D ; Yilmaz, Z ; Jahanshad, N ; Batury, V-L ; Seitz, J ; Bulik, C M ; PGC-ED ; Thompson, P M ; Ehrlich, Stefan. / Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa. In: Molecular Neurobiology. 2019 ; Vol. 56, No. 7. pp. 5146-5156.

Bibtex

@article{e223a5965c2c4cf2ba33b7ef4044f08b,
title = "Exploration of Shared Genetic Architecture Between Subcortical Brain Volumes and Anorexia Nervosa",
abstract = "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 (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 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.",
keywords = "Anorexia nervosa, Brain structure, Genetic correlation",
author = "E Walton and D Hibar and Z Yilmaz and N Jahanshad and V-L Batury and J Seitz and Bulik, {C M} and PGC-ED and Thompson, {P M} and Stefan Ehrlich",
year = "2019",
month = "7",
day = "1",
doi = "10.1007/s12035-018-1439-4",
language = "English",
volume = "56",
pages = "5146--5156",
journal = "Molecular Neurobiology",
issn = "0893-7648",
publisher = "Humana Press",
number = "7",

}

RIS - suitable for import to EndNote

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 - Batury, V-L

AU - Seitz, J

AU - Bulik, C M

AU - PGC-ED

AU - Thompson, P M

AU - Ehrlich, Stefan

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 (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 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 (pFDR = 0.025). Another genetic variant linked to LRRC4C, important in axonal and synaptic development, reached significance after conditioning on hippocampal volume (pFDR = 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

VL - 56

SP - 5146

EP - 5156

JO - Molecular Neurobiology

JF - Molecular Neurobiology

SN - 0893-7648

IS - 7

ER -