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
Center of Excellence in Neurosciences, Department of Biomedical Sciences, Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Department of Health Sciences, College of Health Professions & Social Work, Florida Gulf Coast University, Fort Myers, FL, USA.
Bipolar Disord. 2016 Sep;18(6):520-527. doi: 10.1111/bdi.12438.
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.
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.
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.
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.
近期的全基因组关联研究（GWAS）已鉴定出众多与双相情感障碍（BD）和/或精神分裂症（SC）相关的假定基因多态性。我们推测这些多态性中的一部分在拉丁裔美国人群中也与BD相关。为了识别此类区域，我们在一组患有BD的拉丁裔受试者样本中，对先前鉴定出的与BD和/或SC相关的基因变异以及包含这些单核苷酸多态性（SNP）的祖先单倍型模块进行了检测。
对总共2254名拉丁裔个体进行基因分型，检测先前在BD和/或SC的GWAS中鉴定出的91个SNP，以及与这些标记处于强连锁不平衡状态的选定SNP。使用PBAT软件包进行基于家系的单标记和单倍型关联测试。经验P值来自10000次排列。
8个先验GWAS SNP与BD的关联在名义显著性水平（P≤0.05）上得到了重复。这些包括核因子IA（NFIA）、血清学定义的结肠癌抗原8（SDCCAG8）、溶酶体相关膜蛋白3（LAMP3）、核因子κB亚基1（NFKB1）、主要组织相容性复合体I类B（HLA - B）和胞质5'-核苷酸酶II（NT5C2）内的SNP，以及基因内区域微小RNA 6828（MIR6828）-溶质载体家族7成员14（SLC7A14）和音猬因子（SHH）-长链基因间非编码RNA 1006（LINC01006）内的SNP。在检测与BD关联的76个祖先单倍型模块中，我们最显著关联的单倍型模块位于LAMP3；然而，经Bonferroni校正后，该关联未达到统计学显著性阈值。
这些结果表明，在其他人群中发现与BD或SC相关的一些基因变异在拉丁裔中也与BD风险相关。在我们的拉丁裔样本中，六个基因和两个基因内区域的变异与BD相关，为SC和BD之间的遗传风险重叠提供了额外证据。
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