ArticlePloS one2013
Influence of genetic variation on plasma protein levels in older adults using a multi-analyte panel.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers, 1 of them a synthesis that pooled it.
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Who cites it
42 citing papers in PubMed, 1 synthesis or guideline pooled it, 54 citations in OpenAlex.
- Genome-wide association study of CSF levels of 59 alzheimer's disease candidate proteins: significant associations with proteins involved in amyloid processing and inflammation.PLoS genetics · 2014Pooled it
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- A Module-Level Polygenic Risk Score-Based NetWAS Framework for Identifying AD Genetic Modules Mediated by Amygdala: An ADNI Study.International journal of molecular sciences · 2025Article
- Contextualizing molecular and structural aging across human organs.medRxiv : the preprint server for health sciences · 2025Article
- The Association among Hypothalamic Subnits, Gonadotropic and Sex Hormone Plasmas Levels in Alzheimer's Disease.Brain sciences · 2024Article
- Integrative metabolomics-genomics approach reveals key metabolic pathways and regulators of Alzheimer's disease.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2022Article
- Genetics meets proteomics: perspectives for large population-based studies.Nature reviews. Genetics · 2021Review
- Detecting genetic associations with brain imaging phenotypes in Alzheimer's disease via a novel structured SCCA approach.Medical image analysis · 2020Article
- Genetic association in female stress urinary incontinence based on proteomic findings: a case-control study.International urogynecology journal · 2020Article
- Targeted genetic analysis of cerebral blood flow imaging phenotypes implicates the INPP5D gene.Neurobiology of aging · 2019Article
- Association of Altered Liver Enzymes With Alzheimer Disease Diagnosis, Cognition, Neuroimaging Measures, and Cerebrospinal Fluid Biomarkers.JAMA network open · 2019Article
- Mining Regional Imaging Genetic Associations via Voxel-wise Enrichment Analysis.... IEEE-EMBS International Conference on Biomedical and Health Informatics. IEEE-EMBS International Conference on Biomedical and Health Informatics · 2019Article
- Altered bile acid profile in mild cognitive impairment and Alzheimer's disease: Relationship to neuroimaging and CSF biomarkers.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2019Article
- Omics-based Biomarkers for the Early Alzheimer Disease Diagnosis and Reliable Therapeutic Targets Development.Current neuropharmacology · 2019Article
- Identification of Common and Rare Genetic Variation Associated With Plasma Protein Levels Using Whole-Exome Sequencing and Mass Spectrometry.Circulation. Genomic and precision medicine · 2018Article
- Early Life Stress and Epigenetics in Late-onset Alzheimer's Dementia: A Systematic Review.Current genomics · 2018Review
- CXCL13 polymorphism is associated with essential hypertension in Tatars from Russia.Molecular biology reports · 2018Article
- GPU Accelerated Browser for Neuroimaging Genomics.Neuroinformatics · 2018Article
- A novel SCCA approach via truncated ℓ1-norm and truncated group lasso for brain imaging genetics.Bioinformatics (Oxford, England) · 2018Article
- Pattern Discovery in Brain Imaging Genetics via SCCA Modeling with a Generic Non-convex Penalty.Scientific reports · 2017Article
Corrections and comments
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Authors and funding
19 authors at 8 institutions in 1 country.
Funding
Abstract
Proteins, widely studied as potential biomarkers, play important roles in numerous physiological functions and diseases. Genetic variation may modulate corresponding protein levels and point to the role of these variants in disease pathophysiology. Effects of individual single nucleotide polymorphisms (SNPs) within a gene were analyzed for corresponding plasma protein levels using genome-wide association study (GWAS) genotype data and proteomic panel data with 132 quality-controlled analytes from 521 Caucasian participants in the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. Linear regression analysis detected 112 significant (Bonferroni threshold p=2.44×10(-5)) associations between 27 analytes and 112 SNPs. 107 out of these 112 associations were tested in the Indiana Memory and Aging Study (IMAS) cohort for replication and 50 associations were replicated at uncorrected p<0.05 in the same direction of effect as those in the ADNI. We identified multiple novel associations including the association of rs7517126 with plasma complement factor H-related protein 1 (CFHR1) level at p<1.46×10(-60), accounting for 40 percent of total variation of the protein level. We serendipitously found the association of rs6677604 with the same protein at p<9.29×10(-112). Although these two SNPs were not in the strong linkage disequilibrium, 61 percent of total variation of CFHR1 was accounted for by rs6677604 without additional variation by rs7517126 when both SNPs were tested together. 78 other SNP-protein associations in the ADNI sample exceeded genome-wide significance (5×10(-8)). Our results confirmed previously identified gene-protein associations for interleukin-6 receptor, chemokine CC-4, angiotensin-converting enzyme, and angiotensinogen, although the direction of effect was reversed in some cases. This study is among the first analyses of gene-protein product relationships integrating multiplex-panel proteomics and targeted genes extracted from a GWAS array. With intensive searches taking place for proteomic biomarkers for many diseases, the role of genetic variation takes on new importance and should be considered in interpretation of proteomic results.
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