Publication

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

PGC-ED & ENIGMA Genetics Working Grp, Jul-2019, In : Molecular neurobiology. 56, 7, p. 5146-5156 11 p.

Research output: Contribution to journalArticleAcademicpeer-review

  • PGC-ED
  • ENIGMA Genetics Working Grp

In MRI scans of patientswith anorexia nervosa (AN), reductions in brain volume are often apparent. However, it is unknownwhether such brain abnormalities are influenced by genetic determinants that partially overlap with those underlyingAN. 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 correlationsrangedfrom-0.10to0.23(allp > 0.05). Thereweresomesigns ofaninverseconcordance 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 systemrelevant genes, in particularDRD2, 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.

Original languageEnglish
Pages (from-to)5146-5156
Number of pages11
JournalMolecular neurobiology
Volume56
Issue number7
Publication statusPublished - Jul-2019

    Keywords

  • Anorexia nervosa, Brain structure, Genetic correlation, GENOME-WIDE ASSOCIATION, FUNCTIONAL CONNECTIVITY, MENDELIAN RANDOMIZATION, RESPONSE-INHIBITION, REWARD CIRCUITRY, ADOLESCENT, RISK, POLYMORPHISMS, SCHIZOPHRENIA, ABNORMALITIES

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