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

Fears SC, Service SK, Kremeyer B, Araya C, Araya X, Bejarano J, Ramirez M, Castrillón G, Gomez-Franco J, Lopez MC, Montoya G, Montoya P, Aldana I, Teshiba TM, Al-Sharif NB, Jalbrzikowski M, Tishler TA, Escobar J, Ruiz-Linares A, Lopez-Jaramillo C, Macaya G, Molina J, Reus VI, Cantor RM, Sabatti C, Freimer NB, Bearden CE. Genome-wide mapping of brain phenotypes in extended pedigrees with strong genetic loading for bipolar disorder. Molecular Psychiatry. 2021 Sep 1; 26(9):5229-5238.

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Abstract:

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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