Xu Z, Taylor JA. SNPinfo: integrating GWAS and candidate gene information into functional SNP selection for genetic association studies. Nucleic Acids Res 37: W600-W605

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC 27709, USA.
Nucleic Acids Research (Impact Factor: 9.11). 06/2009; 37(Web Server issue):W600-5. DOI: 10.1093/nar/gkp290
Source: PubMed


We have developed a set of web-based SNP selection tools (freely available at where investigators can specify genes or linkage regions and select SNPs based on GWAS results, linkage disequilibrium (LD), and predicted functional characteristics of both coding and non-coding SNPs. The algorithm uses GWAS SNP P-value data and finds all SNPs in high LD with GWAS SNPs, so that selection is from a much larger set of SNPs than the GWAS itself. The program can also identify and choose tag SNPs for SNPs not in high LD with any GWAS SNP. We incorporate functional predictions of protein structure, gene regulation, splicing and miRNA binding, and consider whether the alternative alleles of a SNP are likely to have differential effects on function. Users can assign weights for different functional categories of SNPs to further tailor SNP selection. The program accounts for LD structure of different populations so that a GWAS study from one ethnic group can be used to choose SNPs for one or more other ethnic groups. Finally, we provide an example using prostate cancer and demonstrate that this algorithm can select a small panel of SNPs that include many of the recently validated prostate cancer SNPs.

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Available from: Zongli Xu, Jun 25, 2015
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    • "QIAamp DNA Mini Kit (Qiagen GmbH, Hilden, Germany). Selection of tag SNPs: tag SNPs were selected for TPH2 using National Institute of Environmental Health Sciences (NIEHS) Tag SNP selection tool using r 2 threshold of 0.8 [31] "
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    ABSTRACT: Heritability plays an important role in the development and expression of alcohol dependence. The present genetic association study explored the role of TPH2 polymorphisms and their haplotypes to investigate its role in alcohol dependence and comorbid psychopathological symptoms. The sample included 101 subjects currently diagnosed as alcohol abusers, 100 abstinent alcohol-dependent subjects and 97 healthy controls. Subjects were genotyped for TPH2 rs4570625, rs1843809, rs7305115, rs4290270. TPH2 genotypes were not associated with alcohol dependence, but GGAA haplotype was less common (p = 0.038) and GTAA and GGGT were more common (p = 0.011 and p = 0.021 respectively) in currently dependent patients compared to controls. Exploratory analysis of genotypes in currently dependent patients showed that rs1843809 was associated with depressive and aggressive traits (p = 0.045 and p = 0.001, respectively), rs4290270 with depressive and anxiety traits (p = 0.040 and p = 0.025, respectively) and rs4570625 with aggressive traits (p = 0.011). In abstinent subjects rs1843809 genotype was associated with traits of social anxiety (p = 0.003). Only association between rs1843809 and the BDHI score (p = 0.001) and associations between GTAA haplotype and Zung Anxiety Scale and BDHI score (p = 0.001 and p < 0.001, respectively) in currently dependent patients remained significant after applying the Bonferroni's correction. Our findings support a potential role of TPH2 in alcohol dependence. TPH2 genetic variability may be also associated with anxiety and aggression traits in alcohol dependent subjects. Copyright © 2015. Published by Elsevier Ireland Ltd.
    Neuroscience Letters 07/2015; 604. DOI:10.1016/j.neulet.2015.07.037 · 2.03 Impact Factor
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    • "[30], GenomePipe (http:// [31] FastSNP (http://fastsnp., "
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    ABSTRACT: Recent evidence suggests immune and inflammatory alterations are important in chronic fatigue syndrome (CFS). This study was done to explore the association of functionally important genetic variants in inflammation and immune pathways with CFS. Peripheral blood DNA was isolated from 50 CFS and 121 non-fatigued (NF) control participants in a population-based study. Genotyping was performed with the Affymetrix Immune and Inflammation Chip that covers 11K single nucleotide polymorphisms (SNP) following the manufacturer's protocol. Genotyping accuracy for specific genes was validated by pyrosequencing. Golden Helix SVS software was used for genetic analysis. SNP functional annotation was done using SPOT and GenomePipe programs. CFS was associated with 32 functionally important SNPs: 11 missense variants, 4 synonymous variants, 11 untranslated regulatory region (UTR) variants and 6 intronic variants. Some of these SNPs were in genes within pathways related to complement cascade (SERPINA5, CFB, CFH, MASP1 and C6), chemokines (CXCL16, CCR4, CCL27), cytokine signaling (IL18, IL17B, IL2RB), and toll-like receptor signaling (TIRAP, IRAK4). Of particular interest is association of CFS with two missense variants in genes of complement activation, rs4151667 (L9H) in CFB and rs1061170 (Y402H) in CFH. A 5'UTR polymorphism (rs11214105) in IL18 also associated with physical fatigue, body pain and score for CFS case defining symptoms. This study identified new associations of CFS with genetic variants in pathways including complement activation providing additional support for altered innate immune response in CFS. Additional studies are needed to validate the findings of this exploratory study. Copyright © 2015. Published by Elsevier Inc.
    Human immunology 06/2015; 77. DOI:10.1016/j.humimm.2015.06.014 · 2.14 Impact Factor
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    • " (Lee & Shatkay 2008) and SNPinfo–FuncPred ( htm/) (Xu & Taylor 2009 "
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    ABSTRACT: Latrophilin 3 (LPHN3) is a brain-specific member of the G-protein coupled receptor family associated to both Attention-Deficit/Hyperactivity Disorder (ADHD) genetic susceptibility and methylphenidate pharmacogenetics.. Interactions of LPHN3 variants with variants harbored in the 11q chromosome improve the prediction of ADHD development and medication response. The aim of the present study was to evaluate the role LPHN3 variants in childhood ADHD susceptibility and treatment response in a naturalistic clinical cohort. The association between LPHN3 and ADHD was evaluated in 523 children and adolescents with ADHD and 132 controls. In the pharmacogenetics study, 172 children with ADHD were investigated. The primary outcome measure was the parent-rated Swanson, Nolan, and Pelham Scale - version IV applied at baseline, first and third months of treatment with methylphenidate. The results reported herein suggest the CGC haplotype derived from SNPs rs6813183, rs1355368, rs734644 as an ADHD risk haplotype (P = 0.02; OR = 1.46). Although non-significant after multiple testing correction, its interaction with the 11q chromosome SNP rs965560 slightly increases risk (nominal P = 0.03; OR = 1.55). Homozygous individuals for the CGC haplotype showed faster response to MPH treatment as a significant interaction effect between CGC haplotype and treatment over time was observed (P < 0.001). Homozygous individuals for the GT haplotype derived from SNPs rs6551665 and rs1947275 showed a significant interaction with treatment over time (nominal P = 0.04). Our findings replicate previous findings reporting that LPHN3 confers ADHD susceptibility, and moderates MPH treatment response in children and adolescents with ADHD. This article is protected by copyright. All rights reserved.
    Genes Brain and Behavior 05/2015; 14(5). DOI:10.1111/gbb.12224 · 3.66 Impact Factor
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