Grace Png's research while affiliated with Helmholtz-Zentrum für Umweltforschung and other places
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Publications (13)
Background
Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.
Methods
We conducted a meta-analysis on genome-wide assoc...
Understanding the genetic basis of neuro-related proteins is essential for dissecting the molecular basis of human behavioral traits and the disease etiology of neuropsychiatric disorders. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The ana...
Background: Human plasma contains a wide variety of circulating proteins. These proteins can be important clinical biomarkers in disease and also possible drug targets. Large scale genomics studies of circulating proteins can identify genetic variants that lead to relative protein abundance.
Methods: We conducted a meta-analysis on genome-wide asso...
Understanding the genetic basis of neuro-related proteins is essential for dissecting the disease etiology of neuropsychiatric disorders and other complex traits and diseases. Here, the SCALLOP Consortium conducted a genome-wide association meta-analysis of over 12,500 individuals for 184 neuro-related proteins in human plasma. The analysis identif...
Cardiometabolic diseases, such as type 2 diabetes and cardiovascular disease, have a high public health burden. Understanding the genetically-determined regulation of proteins that are dysregulated in disease can help to dissect the complex biology underpinning them. Here, we perform a protein quantitative trait locus (pQTL) analysis of 255 serum p...
Background: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the etiologic agent of COVID-19, enters human cells using the angiotensin-converting enzyme 2 (ACE2) protein as a receptor. ACE2 is thus key to the infection and treatment of the coronavirus. ACE2 is highly expressed in the heart, respiratory and gastrointestinal tracts, play...
Objective
Deep sequencing offers unparalleled access to rare variants in human populations. Understanding their role in disease is a priority, yet prohibitive sequencing costs mean that many cohorts lack the sample size to discover these effects on their own. Meta-analysis of individual variant scores allows the combination of rare variants across...
Despite the increasing global burden of neurological disorders, there is a lack of effective diagnostic and therapeutic biomarkers. Proteins are often dysregulated in disease and have a strong genetic component. Here, we carry out a protein quantitative trait locus analysis of 184 neurologically-relevant proteins, using whole genome sequencing data...
The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we comprehensively assess the genetic architecture of 257 circulating protein biomarkers of cardiometabolic relevance through high-depth (22.5×) whole-genome...
Front Cover Caption: The cover image is based on the Original Article Population‐wide copy number variation calling using variant call format files from 6,898 individuals by Arthur Gilly et al., https://doi.org/10.1002/gepi.22260.
The human proteome is a crucial intermediate between complex diseases and their genetic and environmental components, and an important source of drug development targets and biomarkers. Here, we conduct high-depth (22.5x) whole-genome sequencing (WGS) in 1,328 individuals to fully assess the genetic architecture of 257 circulating protein biomarker...
Copy number variants (CNVs) play an important role in a number of human diseases, but the accurate calling of CNVs remains challenging. Most current approaches to CNV detection use raw read alignments, which are computationally intensive to process. We use a regression tree‐based approach to call germline CNVs from whole‐genome sequencing (WGS, >18...
Motivation
Copy number variants (CNVs) are large deletions or duplications at least 50 to 200 base pairs long. They play an important role in multiple disorders, but accurate calling of CNVs remains challenging. Most current approaches to CNV detection use raw read alignments, which are computationally intensive to process.
Results
We use a regres...
Citations
... APR may therefore have inhibitory effects on sulfatase activity through increased levels of SUMF2, a protein that has not been investigated in clinical trials to date. Causal associations between SUMF2 and LDL cholesterol, total cholesterol, triglyceride levels and HDL cholesterol have been reported in a study exploring relationships between cardiometabolic traits and serum proteins 42 . In the present study we report correlation of SUMF2 with metabolites including VLDL, LDL and HDL particles and percentages, and with TG by PG ratio ( Table 2). ...
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... Their primary focus has been the identification of common [minor allele frequency (MAF) > 0.01] variants affecting inter-individual protein variability, but Sun et al. 9 reported that approximately 5.6% (570/10,248) and 1.5% (155/10,248) of the variants with primary associations had MAFs < 0.01 and < 0.005, respectively. In addition, the focus has been shifting toward the identification of associations with rare (MAF < 0.01) variants, using gene-based methods [10][11][12][13][14] . For example, a recent landmark study conducted on the Icelandic population revealed 18,084 genetic associations with protein levels, 19% of which were with rare variants 8 . ...
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... So far, the approaches to identify ACE2 variants potentially associated with phenotypic traits have relied on genome-wide association studies (GWAS) or case-control approaches (Yang et al., 2022b;Pan et al., 2018;Fan et al., 2019), and this has allowed the detection of variants whose functional impact has not been fully clarified. ...
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... [36] A recent study involving 979 participants showed that changes in eight proteins in the CSF could accurately distinguish patients with AD and MCI (Ab positive) from controls and that changes in MMP-10, TGB2, and TREM1 were specific to AD. [37] The accessibility of peripheral samples such as plasma has led to the preference for using plasma samples in biomarker studies employing PEA. Among studies focusing on AD, four studies used only plasma, [38][39][40][41] two studies used both plasma and CSF, [31,42] and one study used extracellular vesicles [43] as the source of samples. The patient groups exhibited a wide variability in studies using plasma samples. ...
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... The dataset pertaining to HbA1c and TG originated from a GWAS study undertaken by Howe LJ et al., involving 182,416 and 69,360 European males and females, respectively. The IVs with regard to FGF21 were extracted from a GWAS study conducted by Gilly et al. (32), which identified 18,160,173 single nucleotide polymorphisms (SNPs) among 1,298 samples. In addition, aggregate data regarding external smoke exposure, physical activity, EA, participation in sports clubs or gym leisure activities, and TDI were obtained from the Neale Lab or MRC-IEU consortium. ...
... An important issue linked to blood analysis is the underlying effect of genetics to determine stable differences in protein levels between individuals. The levels of blood proteins have previously been determined to be influenced both by genetic and environmental factors, as studied by mass spectrometry-based proteomics [1][2][3][4], nucleic-acid based assays [5][6][7][8], and immuno-based assays [9][10][11][12][13][14]. Effects based on sex [15], specific diets [15], age [16], and infections [17] have also been reported suggesting an important role for quantitative blood protein assays for individualized diagnosis of health and disease. ...
... For example, a recent landmark study conducted on the Icelandic population revealed 18,084 genetic associations with protein levels, 19% of which were with rare variants 8 . Investigation of the effects of other structural variants, such as copy number variants (CNVs), on protein levels has thus far been limited 15 . ...
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