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Genome-wide association analysis of the human thalamus identifies novel genomic loci and reveals genetic overlap with distinct cortical regions and ten brain disorders

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Kumar, VJ
Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society;
Max Planck Institute for Biological Cybernetics, Max Planck Society;

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Citation

Elvsåshagen, T., Shadrin, A., Frei, O., van der Meer, D., Bahrami, S., Kumar, V., et al. (submitted). Genome-wide association analysis of the human thalamus identifies novel genomic loci and reveals genetic overlap with distinct cortical regions and ten brain disorders.

Abstract

The thalamus is a vital communication hub in the center of the brain and consists of distinct nuclei critical for consciousness and higher-order cortical functions1-8. Structural and functional thalamic alterations are involved in the pathogenesis of common brain disorders9-12, yet the genetic architecture of the thalamus remains largely unknown. Here, using brain scans and genotype data from 30,114 individuals, we identified 42 (41 novel) genetic loci and 392 genes associated with volumes of the thalamus and its nuclei. In an independent validation sample (n = 5,173) 96% of the loci showed the same effect direction (sign test, P = 8.6e-14). We mapped the genetic relationship between thalamic nuclei and 180 cerebral cortical areas and found overlapping genetic architectures consistent with thalamocortical connectivity. Pleiotropy analyses between thalamic volumes and ten psychiatric and neurological disorders revealed shared variants for all disorders. Together, these analyses identify the first genetic loci linked to thalamic nuclei and substantiate the emerging view of the thalamus having central roles in cortical functioning and common brain disorders.