Systematic Review and Meta-Analysis of the Association Between Complement Component 3 and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis

Thakkinstian, Ammarin; McKay, Gareth J.; McEvoy, Mark; Chakravarthy, Usha; Chakrabarti, Subhabrata; Silvestri, G; Kaur, Inderjeet; Li, Xiaoxin; Attia, John

doi:10.1093/aje/kwr025

Cited by 127 publications

(110 citation statements)

References 88 publications

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“…In our data, we detected variants that have previously been associated with disease in man. For instance, rs1047286 showing an association with peptide levels in the C3 gene, has previously been associated with increased risk of age-related macular degeneration (24). The peptide with an amino acid change caused by this polymorphism was detected in our data (Table 1).…”

Section: Discussionsupporting

confidence: 58%

Identification of genetic variants influencing the human plasma proteome

Johansson

Enroth

Palmblad

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Genetic variants influencing the transcriptome have been extensively studied. However, the impact of the genetic factors on the human proteome is largely unexplored, mainly due to lack of suitable high-throughput methods. Here we present unique and comprehensive identification of genetic variants affecting the human plasma protein profile by combining high-throughput and highresolution mass spectrometry (MS) with genome-wide SNP data. We identified and quantified the abundance of 1,056 trypticdigested peptides, representing 163 proteins in the plasma of 1,060 individuals from two population-based cohorts. The abundance level of almost one-fifth (19%) of the peptides was found to be heritable, with heritability ranging from 0.08 to 0.43. The levels of 60 peptides from 25 proteins, 15% of the proteins studied, were influenced by cis-acting SNPs. We identified and replicated individual cis-acting SNPs (combined P value ranging from 3.1 × 10 −52 to 2.9 × 10 −12 ) influencing 11 peptides from 5 individual proteins. These SNPs represent both regulatory SNPs and nonsynonymous changes defining well-studied disease alleles such as the e4 allele of apolipoprotein E (APOE), which has been shown to increase risk of Alzheimer's disease. Our results show that high-throughput mass spectrometry represents a promising method for large-scale characterization of the human proteome, allowing for both quantification and sequencing of individual proteins. Abundance and peptide composition of a protein plays an important role in the etiology, diagnosis, and treatment of a number of diseases. A better understanding of the genetic impact on the plasma proteome is therefore important for evaluating potential biomarkers and therapeutic agents for common diseases.protein quantitative trait loci | population proteomics O ur understanding of the impact of genetic variation on human traits has been greatly advanced using high-throughput SNP genotyping and massively parallel sequencing. The large number of genome-wide association studies (GWAS) performed have resulted in the identification of hundreds of SNPs that are associated with human traits and diseases (1, 2). The functional impact of most of the SNPs influencing human traits has not been well characterized. Whereas nonsynonymous SNPs affect the amino acid sequence directly and could alter the function of the resulting protein, other SNPs may have an impact on splice sites (3) or influence amount or stability of the mRNA (4). GWAS studies relating the genetic variability to the transcript profile have identified a number of cis-regulatory SNPs affecting expression quantitative traits (eQTs) (5, 6). Evidently, the expression of many genes is influenced by a nearby SNP, with cis-regulatory SNPs being overrepresented among SNPs associated with human phenotypes (1). Studies have also addressed the impact of genetic variability on levels of endogenous metabolites, such as sugars, biogenic amines, acylcarnitines, and glycerophospho-and sphingolipids, which can be measured in either human urin...

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Section: Discussionsupporting

confidence: 58%

Identification of genetic variants influencing the human plasma proteome

Johansson

Enroth

Palmblad

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…The quality of each study was assessed by the same two investigators using the quality assessment criteria, which was modified on the basis of previously published metaanalysis of molecular association studies (Thakkinstian et al, 2011;Yu et al, 2012). The criteria consist of seven parameters of quality: representativeness of the cases, representativeness of the controls, ascertainment of bladder cancers, control selection, genotyping examination, Hardy-Weinberg equilibrium, and total sample size (The criteria are described in detail in Table 1).…”

Section: Quality Assessmentmentioning

confidence: 99%

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

Guo¹,

Feng²

2012

Asian Pacific Journal of Cancer Prevention

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“…Study quality was assessed using a risk-of-bias score for genetic association studies developed by Thakkinstian et al (2011) (Table S1). The assessment considered five domains: information bias, confounding bias, selective reporting of outcomes, population stratification, and assessment of HWE in the control group.…”

Section: Assessment Of Bias Riskmentioning

confidence: 99%

Association between IL2/IL21 and SH2B3 polymorphisms and risk of celiac disease: a meta-analysis

Guo¹,

Huang²,

N³

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Celiac disease (CD) is a common autoimmune disorder characterized by heightened immunological response to ingested gluten. Certain gene polymorphisms of IL2/IL21 (rs6822844 and rs6840978) and SH2B3 (rs3184504) may influence susceptibility to CD, although the effects remain unclear. We performed a meta-analysis of the associations between rs6822844, rs6840978, and rs3184504 polymorphisms and CD risk. PubMed, EMBASE, and the China National Knowledge Infrastructure were searched. ORs and 95%CIs of each single nucleotide polymorphism (SNP) were estimated using the fixed-effect model if I 2 < 50% in the test of heterogeneity; otherwise, the random-effect model was used. Our meta-analysis included 12,986 CD cases and 28,733 controls from 16 independent samples, and the analysis of each SNP contained a subset of the total. We found that the minor allele T of both rs6822844 (T vs G, OR (2015) = 0.72, 95%CI = 0.67-0.78, P < 0.001) and rs6840978 (T vs C, OR = 0.76, 95%CI = 0.71-0.83, P < 0.001) in IL2/IL21 significantly decreased the risk of CD. However, the minor allele A of rs3184504 (A vs G, OR = 1.18, 95%CI = 1.12-1.24, P < 0.001) in SH2B3 significantly increased CD susceptibility. The estimated lambda values were 0.49, 0.50, and 0.53 for rs6822844, rs6840978, and rs3184504, respectively, suggesting that a co-dominant model of genotype effect was most appropriate for the three SNPs. Our results support associations between the three SNPs and CD and provide a strong argument for further research.

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Systematic Review and Meta-Analysis of the Association Between Complement Component 3 and Age-related Macular Degeneration: A HuGE Review and Meta-Analysis

Cited by 127 publications

References 88 publications

Identification of genetic variants influencing the human plasma proteome

Identification of genetic variants influencing the human plasma proteome

The NQO1 rs1800566 Polymorphism and Risk of Bladder Cancer: Evidence from 6,169 Subjects

Association between IL2/IL21 and SH2B3 polymorphisms and risk of celiac disease: a meta-analysis

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