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

Scott C Fears; Susan K Service; Barbara Kremeyer; Carmen Araya; Xinia Araya; Julio Bejarano; Margarita Ramirez; Gabriel Castrillón; Juliana Gomez-Franco; Maria C Lopez; Gabriel Montoya; Patricia Montoya; Ileana Aldana; Terri M Teshiba; Noor B Al-Sharif; Maria Jalbrzikowski; Todd A Tishler; Javier Escobar; Andrés Ruiz-Linares; Carlos Lopez-Jaramillo; Gabriel Macaya; Julio Molina; Victor I Reus; Rita M Cantor; Chiara Sabatti; Nelson B Freimer; Carrie E Bearden

doi:10.1038/s41380-020-0805-6

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

Mol Psychiatry. 2021 Sep;26(9):5229-5238. doi: 10.1038/s41380-020-0805-6. Epub 2020 Jun 30.

Authors

Scott C Fears^{1

2

3}, Susan K Service^{4

5}, Barbara Kremeyer⁶, Carmen Araya⁷, Xinia Araya⁷, Julio Bejarano⁷, Margarita Ramirez⁷, Gabriel Castrillón⁸, Juliana Gomez-Franco⁹, Maria C Lopez¹⁰, Gabriel Montoya¹⁰, Patricia Montoya¹⁰, Ileana Aldana⁴, Terri M Teshiba⁴, Noor B Al-Sharif⁴, Maria Jalbrzikowski⁴, Todd A Tishler⁴, Javier Escobar¹¹, Andrés Ruiz-Linares^{12

13

14}, Carlos Lopez-Jaramillo¹⁰, Gabriel Macaya⁷, Julio Molina^{4

15}, Victor I Reus¹⁶, Rita M Cantor^{4

17}, Chiara Sabatti¹⁸, Nelson B Freimer^{4

5}, Carrie E Bearden^{4

5}

Affiliations

¹ Department of Psychiatry and Biobehavioral Science, University of California, Los Angeles, CA, USA. [email protected].
² Section of Mental Health, Greater Los Angeles Veterans Administration, Los Angeles, CA, USA. [email protected].
³ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA. [email protected].
⁴ Department of Psychiatry and Biobehavioral Science, University of California, Los Angeles, CA, USA.
⁵ Center for Neurobehavioral Genetics, Semel Institute for Neuroscience and Human Behavior, Los Angeles, CA, USA.
⁶ Department of Genetics, Evolution and Environment, University College London, London, WC1E 6BT, UK.
⁷ Cell and Molecular Biology Research Center, Universidad de Costa Rica, San Pedro de Montes de Oca, Costa Rica.
⁸ Insituto de Alta Tecnologìa Mèdica, Medellín, Colombia.
⁹ Department of Psychiatry, Harbor-UCLA Hospital, Los Angeles, CA, USA.
¹⁰ Grupo de Investigación en Psiquiatría (Research Group in Psychiatry (GIPSI)), Departamento de Psiquiatría, Facultad de Medicina, Universidad de Antioquia, Medellín, Colombia.
¹¹ Department of Psychiatry and Family Medicine, Rutgers-Robert Wood Johnson Medical School, New Brunswick, New Jersey, USA.
¹² Ministry of Education Key Laboratory of Contemporary Anthropology and Collaborative Innovation Center of Genetics and Development, School of Life Sciences and Human Phenome Institute, Fudan University, Yangpu District, Shanghai, China.
¹³ UMR 7268 ADES, CNRS, Aix-Marseille Université, EFS, Faculté de médecine Timone, Marseille, 13005, France.
¹⁴ Department of Genetics, Evolution and Environment, and UCL Genetics Institute, University College London, London, WC1E 6BT, UK.
¹⁵ BioCiencias Lab, Guatemala, Guatemala.
¹⁶ Department of Psychiatry, University of California, San Francisco, CA, USA.
¹⁷ Department of Human Genetics, University of California, Los Angeles, CA, USA.
¹⁸ Department of Health Research and Policy, Stanford University, Stanford, CA, USA.

PMID: 32606377
DOI: 10.1038/s41380-020-0805-6

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Bipolar Disorder* / genetics
Brain / diagnostic imaging
Genetic Linkage / genetics
Humans
Pedigree
Phenotype
Quantitative Trait Loci / genetics

Abstract

Publication types

MeSH terms

Grants and funding