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Replication of genome‐wide association study ( GWAS ) susceptibility loci in a Latino bipolar disorder cohort
Author(s) -
Gonzalez Suzanne,
Gupta Jayanta,
Villa Erika,
Mallawaarachchi Indika,
Rodriguez Marco,
Ramirez Mercedes,
Zavala Juan,
Armas Regina,
Dassori Albana,
Contreras Javier,
Flores Deborah,
Jerez Alvaro,
Ontiveros Alfonso,
Nicolini Humberto,
Escamilla Michael
Publication year - 2016
Publication title -
bipolar disorders
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.285
H-Index - 129
eISSN - 1399-5618
pISSN - 1398-5647
DOI - 10.1111/bdi.12438
Subject(s) - genome wide association study , single nucleotide polymorphism , genetics , linkage disequilibrium , biology , genetic association , snp , haplotype , bipolar disorder , allele , genotype , gene , cognition , neuroscience
Objectives Recent genome‐wide association studies ( GWAS s) have identified numerous putative genetic polymorphisms associated with bipolar disorder ( BD ) and/or schizophrenia ( SC ). We hypothesized that a portion of these polymorphisms would also be associated with BD in the Latino American population. To identify such regions, we tested previously identified genetic variants associated with BD and/or SC and ancestral haploblocks containing these single nucleotide polymorphisms ( SNP s) in a sample of Latino subjects with BD . Methods A total of 2254 Latino individuals were genotyped for 91 SNP s identified in previous BD and/or SC GWAS s, along with selected SNP s in strong linkage disequilibrium with these markers. Family‐based single marker and haplotype association testing was performed using the PBAT software package. Empirical P ‐values were derived from 10 000 permutations. Results Associations of eight a priori GWAS SNP s with BD were replicated with nominal ( P ≤.05) levels of significance. These included SNP s within nuclear factor I A ( NFIA ), serologically defined colon cancer antigen 8 ( SDCCAG 8 ), lysosomal associated membrane protein 3 ( LAMP 3 ), nuclear factor kappa B subunit 1 ( NFKB 1 ), major histocompatibility complex, class I, B ( HLA ‐B ) and 5′‐nucleotidase, cytosolic II ( NT 5C2 ) and SNP s within intragenic regions microRNA 6828 ( MIR 6828 ) — solute carrier family 7 member 14 ( SLC 7A14 ) and sonic hedgehog ( SHH ) — long intergenic non‐protein coding RNA 1006 ( LINC 01006 ). Of the 76 ancestral haploblocks that were tested for associations with BD , our top associated haploblock was located in LAMP 3 ; however, the association did not meet statistical thresholds of significance following Bonferroni correction. Conclusions These results indicate that some of the gene variants found to be associated with BD or SC in other populations are also associated with BD risk in Latinos. Variants in six genes and two intragenic regions were associated with BD in our Latino sample and provide additional evidence for overlap in genetic risk between SC and BD .