Genome-wide mapping of brain phenotypes in extended pedigrees with strong genetic loading for bipolar disorder


Bipolar disorder is a highly heritable illness, associated with alterations of brain structure. As such, identification of genes influencing inter-individual differences in brain morphology may help elucidate the underlying pathophysiology of bipolar disorder (BP). To identify quantitative trait loci (QTL) that contribute to phenotypic variance of brain structure, structural neuroimages were acquired from family members (n = 527) of extended pedigrees heavily loaded for bipolar disorder ascertained from genetically isolated populations in Latin America. Genome-wide linkage and association analysis were conducted on the subset of heritable brain traits that showed significant evidence of association with bipolar disorder (n = 24) to map QTL influencing regional measures of brain volume and cortical thickness. Two chromosomal regions showed significant evidence of linkage; a QTL on chromosome 1p influencing corpus callosum volume and a region on chromosome 7p linked to cortical volume. Association analysis within the two QTLs identified three SNPs correlated with the brain measures.

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Fig. 1: Top linkage results for each of the 24 BP-associated brain phenotypes.
Fig. 2: Results of association testing within the two significant linkage regions.


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We wish to thank our late colleagues Lori Altshuler MD and George Bartzokis MD for their valuable input and guidance on this work.


This research was supported by National Institute of Health Grants R01MH075007, R01MH095454, P30NS062691; (NBF), K23MH074644-01; (CEB) R01HG006695; (CS), and K08MH086786 (SCF), the Joanne and George Miller Family Endowed Term Chair (CEB), and Colciencias and Codi-University of Antioquia (CL-J).

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Fears, S.C., Service, S.K., Kremeyer, B. et al. Genome-wide mapping of brain phenotypes in extended pedigrees with strong genetic loading for bipolar disorder. Mol Psychiatry (2020).

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