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

Suzanne Gonzalez, Jayanta Gupta, Erika Villa, Indika Mallawaarachchi, Marco Rodriguez, Mercedes Ramirez, Juan Zavala, Regina Armas, Albana Dassori, Javier Contreras, Deborah Flores, Alvaro Jerez, Alfonso Ontiveros, Humberto Nicolini, Michael Escamilla

Research output: Contribution to journalArticle

6 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)520-527
Number of pages8
JournalBipolar Disorders
Volume18
Issue number6
DOIs
StatePublished - Sep 1 2016

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Genome-Wide Association Study
Bipolar Disorder
Hispanic Americans
Single Nucleotide Polymorphism
Lysosomal-Associated Membrane Protein 3
Schizophrenia
NFI Transcription Factors
Long Noncoding RNA
5'-Nucleotidase
HLA-B Antigens
NF-kappa B
Linkage Disequilibrium
Genetic Polymorphisms
Major Histocompatibility Complex
MicroRNAs
Colonic Neoplasms
Haplotypes
Population
Genes
Software

All Science Journal Classification (ASJC) codes

  • Psychiatry and Mental health
  • Biological Psychiatry

Cite this

Gonzalez, S., Gupta, J., Villa, E., Mallawaarachchi, I., Rodriguez, M., Ramirez, M., ... Escamilla, M. (2016). Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort. Bipolar Disorders, 18(6), 520-527. https://doi.org/10.1111/bdi.12438
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. / Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort. In: Bipolar Disorders. 2016 ; Vol. 18, No. 6. pp. 520-527.
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abstract = "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.",
author = "Suzanne Gonzalez and Jayanta Gupta and Erika Villa and Indika Mallawaarachchi and Marco Rodriguez and Mercedes Ramirez and Juan Zavala and Regina Armas and Albana Dassori and Javier Contreras and Deborah Flores and Alvaro Jerez and Alfonso Ontiveros and Humberto Nicolini and Michael Escamilla",
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Gonzalez, S, Gupta, J, Villa, E, Mallawaarachchi, I, Rodriguez, M, Ramirez, M, Zavala, J, Armas, R, Dassori, A, Contreras, J, Flores, D, Jerez, A, Ontiveros, A, Nicolini, H & Escamilla, M 2016, 'Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort', Bipolar Disorders, vol. 18, no. 6, pp. 520-527. https://doi.org/10.1111/bdi.12438

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

In: Bipolar Disorders, Vol. 18, No. 6, 01.09.2016, p. 520-527.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Replication of genome-wide association study (GWAS) susceptibility loci in a Latino bipolar disorder cohort

AU - Gonzalez, Suzanne

AU - Gupta, Jayanta

AU - Villa, Erika

AU - Mallawaarachchi, Indika

AU - Rodriguez, Marco

AU - Ramirez, Mercedes

AU - Zavala, Juan

AU - Armas, Regina

AU - Dassori, Albana

AU - Contreras, Javier

AU - Flores, Deborah

AU - Jerez, Alvaro

AU - Ontiveros, Alfonso

AU - Nicolini, Humberto

AU - Escamilla, Michael

PY - 2016/9/1

Y1 - 2016/9/1

N2 - 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.

AB - 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.

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