Replication of genome‐wide association study ( GWAS ) susceptibility loci in a Latino bipolar disorder cohort

Autor: Michael Escamilla, Jayanta Gupta, Javier Contreras, Regina Armas, Suzanne Gonzalez, Humberto Nicolini, Indika Mallawaarachchi, Deborah Flores, Mercedes Ramirez, Juan Zavala, Marco Rodriguez, Alfonso Ontiveros, Erika Villa, Alvaro Jerez, Albana M Dassori
Rok vydání: 2016
Předmět:
Male
0301 basic medicine
Linkage disequilibrium
Bipolar Disorder
serologically defined colon cancer antigen 8 (SDCCAG8)
Genome-wide association study
lysosomal associated membrane protein 3 (LAMP3)
Linkage Disequilibrium
genetics
Genetics
medicine.diagnostic_test
Mexican
Hispanic or Latino
Guatemala
Neoplasm Proteins
3. Good health
Psychiatry and Mental health
NFIA
Female
Original Article
Adult
Costa Rica
Kruppel-Like Transcription Factors
Single-nucleotide polymorphism
family studies
Biology
Polymorphism
Single Nucleotide
03 medical and health sciences
medicine
Humans
Genetic Predisposition to Disease
Genetic Testing
Latinos
Mexico
Gene
Biological Psychiatry
Genetic testing
Genetic association
Mexican‐American
Central American
Haplotype
Lysosome-Associated Membrane Glycoproteins
NF-kappa B p50 Subunit
Original Articles
United States
030104 developmental biology
Haplotypes
Schizophrenia
nuclear factor kappa B subunit 1 (NFKB1)
Genome-Wide Association Study
Zdroj: Bipolar Disorders
ISSN: 1399-5618
1398-5647
DOI: 10.1111/bdi.12438
Popis: Objectives Recent genome-wide association studies (GWASs) 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 (SNPs) in a sample of Latino subjects with BD. Methods A total of 2254 Latino individuals were genotyped for 91 SNPs identified in previous BD and/or SC GWASs, along with selected SNPs 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 SNPs with BD were replicated with nominal (P≤.05) levels of significance. These included SNPs within nuclear factor I A (NFIA), serologically defined colon cancer antigen 8 (SDCCAG8), lysosomal associated membrane protein 3 (LAMP3), nuclear factor kappa B subunit 1 (NFKB1), major histocompatibility complex, class I, B (HLA-B) and 5′-nucleotidase, cytosolic II (NT5C2) and SNPs within intragenic regions microRNA 6828 (MIR6828)—solute carrier family 7 member 14 (SLC7A14) and sonic hedgehog (SHH)—long intergenic non-protein coding RNA 1006 (LINC01006). Of the 76 ancestral haploblocks that were tested for associations with BD, our top associated haploblock was located in LAMP3; 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.
Databáze: OpenAIRE
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