Abstract:
Background: Bipolar disorder (BD) is highly heritable, polygenic, multifactorial, and has complex genetic heterogeneity.
This study aimed to identify rare variants contributing to the aetiology of BD in a consanguineous
family from Pakistan.
Methods: Genome-wide SNP microarray and whole exome sequencing (WES) were used for variant identification
in a large BD-affected consanguineous Pakistani family.
Results: In family BF04, we identified three main regions of homozygosity-by-descent (HBD) over 1 Mb in length,
by far the largest being a 43.6 Mb segment on chromosome 7, and, through WES analysis, found one promising
novel homozygous variant in RELN (NM_005045; c.2090G>A; p.(Gly697Asp)), within this HBD region segregating
in all the BD-affected members.
Conclusion: Based on the clinical and genetic data, the present familial study revealed the plausible contribution
of a novel variant of RELN in association with BD in the affected family. The present study's findings are valuable
in understanding the genetic basis of the multifactorial phenotype BD and pave a better path for future functional
studies.
