Identification of Novel Genomic Variations in Susceptibility to Nonsyndromic Cleft Lip and Palate Patients

Background: Nonsyndromic cleft lip with or without palate (NSCL/P) is a multifactorial and common birth malformation caused by genetic and environmental factors, as well as by teratogens. Genome-wide association studies found genetic variations with modulatory effects of NSCL/P formation in Chinese and Iranian populations. We aimed to identify the susceptibility of single-nucleotide polymorphisms (SNPs) to nonsyndromic cleft lip with or without palate in the Indian population. Material and Methods: The present study was conducted on NSCL/P cases and controls. Genomic DNA was extracted from peripheral blood and Axiom- Precision Medicine Research Array (PMRA) was performed. The Axiom-PMRA covers 902,527 markers and several thousand novel risk variants. Quality control-passed samples were included for candidate genetic variation identification, gene functional enrichment, and pathway and network analysis. Results: The genome-wide association study identified fourteen novel candidate gene SNPs that showed the most significant association with the risk of NSCL/P, and eight were predicted to have regulatory sequences. Conclusion: The GWAS study showed novel candidate genetic variations in NSCL/P formations. These findings contribute to the understanding of genetic predisposition to nonsyndromic cleft lip with or without palate.

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Genome-Wide Association Studies in Dogs and Humans Identify ADAMTS20 as a Risk Variant for Cleft Lip and Palate

PLoS Genetics ◽

10.1371/journal.pgen.1005059 ◽

2015 ◽

Vol 11 (3) ◽

pp. e1005059 ◽

Cited By ~ 55

Author(s):

Zena T. Wolf ◽

Harrison A. Brand ◽

John R. Shaffer ◽

Elizabeth J. Leslie ◽

Boaz Arzi ◽

...

Keyword(s):

Cleft Lip ◽

Cleft Lip And Palate ◽

Association Studies ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Risk Variant ◽

Genome Wide

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Genetic variations and risk of placental abruption: A genome-wide association study and meta-analysis of genome-wide association studies

Placenta ◽

10.1016/j.placenta.2018.04.008 ◽

2018 ◽

Vol 66 ◽

pp. 8-16 ◽

Cited By ~ 2

Author(s):

Tsegaselassie Workalemahu ◽

Daniel A. Enquobahrie ◽

Bizu Gelaye ◽

Sixto E. Sanchez ◽

Pedro J. Garcia ◽

...

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Placental Abruption ◽

Association Studies ◽

Meta Analysis ◽

Genetic Variations ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

A Genome

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Genomic Variations in Susceptibility to Intracranial Aneurysm in the Korean Population

Journal of Clinical Medicine ◽

10.3390/jcm8020275 ◽

2019 ◽

Vol 8 (2) ◽

pp. 275 ◽

Cited By ~ 8

Author(s):

Eun Hong ◽

Bong Kim ◽

Steve Cho ◽

Jin Yang ◽

Hyuk Choi ◽

...

Keyword(s):

Intracranial Aneurysm ◽

Association Studies ◽

Large Population ◽

Genome Wide Association ◽

Korean Population ◽

Genome Wide Association Studies ◽

Medicine Research ◽

Genome Wide ◽

A Genome ◽

Significant Difference

Genome-wide association studies found genetic variations with modulatory effects for intracranial aneurysm (IA) formations in European and Japanese populations. We aimed to identify the susceptibility of single nucleotide polymorphisms (SNPs) to IA in a Korean population consisting of 250 patients, and 294 controls using the Asian-specific Axiom Precision Medicine Research Array. Twenty-nine SNPs reached a genome-wide significance threshold (5 × 10−8). The rs371331393 SNP, with a stop-gain function of ARHGAP32 (11q24.3), showed the most significant association with the risk of IA (OR = 43.57, 95% CI: 21.84–86.95; p = 9.3 × 10−27). Eight out of 29 SNPs—GBA (rs75822236), TCF24 (rs112859779), OLFML2A (rs79134766), ARHGAP32 (rs371331393), CD163L1 (rs138525217), CUL4A (rs74115822), LOC102724084 (rs75861150), and LRRC3 (rs116969723)—demonstrated sufficient statistical power greater than or equal to 0.8. Two previously reported SNPs, rs700651 (BOLL, 2q33.1) and rs6841581 (EDNRA, 4q31.22), were validated in our GWAS (Genome-wide association study). In a subsequent analysis, three SNPs showed a significant difference in expressions: the rs6741819 (RNF144A, 2p25.1) was down-regulated in the adrenal gland tissue (p = 1.5 × 10−6), the rs1052270 (TMOD1. 9q22.33) was up-regulated in the testis tissue (p = 8.6 × 10−10), and rs6841581 (EDNRA, 4q31.22) was up-regulated in both the esophagus (p = 5.2 × 10−12) and skin tissues (1.2 × 10−6). Our GWAS showed novel candidate genes with Korean-specific variations in IA formations. Large population based studies are thus warranted.

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Adaptive growth homeostasis in response to drought in Iberian Arabidopsis accessions

10.1101/2021.05.07.443185 ◽

2021 ◽

Author(s):

Ángel Ferrero-Serrano ◽

Sarah M Assmann

Keyword(s):

Leaf Area ◽

Stress Responses ◽

Association Studies ◽

Transport Processes ◽

Functional Enrichment ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Intrinsic Water Use Efficiency

Plants respond to environmental fluctuations through plastic phenotypic shifts. Whether a plastic response upon environmental variability is adaptive or not has been subject to debate. Using a set of Iberian Arabidopsis accessions, we quantified an interplay between passive plastic reductions in leaf areas that we found typical of accessions from productive environments and homeostatic leaf areas responses to drought typified by accessions originating from unproductive environments. Results from Genome-Wide Association Studies (GWAS) and Transcriptome Wide Association Studies (TWAS) highlight the role of auxin-related processes and, in particular, the possible role of the SMALL AUXIN UP RNA 26 (SAUR26) gene in the regulation of the observed plastic responses. Homeostatic responses in leaf area potential following drought were typical of accessions with lower leaf area potential under well-watered conditions. Transcripts that were negatively associated with leaf area potential and positively associated with homeostatic and positive leaf area plasticity following drought showed functional enrichment in ion transport processes. We hypothesized that the contrasting plastic and homeostatic responses in leaf area potential were associated with differential intrinsic water use efficiency (WUEi). We confirmed this relationship in a metanalysis conducted using previously published δ13C measurements. Our results highlight the adaptive role of homeostatic leaf area response to water depletion arising from increased WUEi. The concerted utilization of Genome-Wide Association Studies (GWAS), Transcriptome Wide Association Studies (TWAS), and expression Genome-Wide Association Studies (eGWAS) allows integration of phenotype, genotype, and transcript abundance to identify both "plasticity genes" and "homeostasis genes" associated with drought stress responses.

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Genetic Dissection of Mature Root Characteristics by Genome-Wide Association Studies in Rapeseed (Brassica napus L.)

Plants ◽

10.3390/plants10122569 ◽

2021 ◽

Vol 10 (12) ◽

pp. 2569

Author(s):

Sani Ibrahim ◽

Keqi Li ◽

Nazir Ahmad ◽

Lieqiong Kuang ◽

Salisu Bello Sadau ◽

...

Keyword(s):

Brassica Napus ◽

Root Development ◽

Association Studies ◽

Genetic Variations ◽

Genome Wide Association ◽

Phenotypic Variance ◽

Genome Wide Association Studies ◽

Root Characteristics ◽

Genome Wide ◽

Mature Root

Roots are complicated quantitative characteristics that play an essential role in absorbing water and nutrients. To uncover the genetic variations for root-related traits in rapeseed, twelve mature root traits of a Brassica napus association panel were investigated in the field within three environments. All traits showed significant phenotypic variation among genotypes, with heritabilities ranging from 55.18% to 79.68%. Genome-wide association studies (GWAS) using 20,131 SNPs discovered 172 marker-trait associations, including 103 significant SNPs (−log10 (p) > 4.30) that explained 5.24–20.31% of the phenotypic variance. With the linkage disequilibrium r2 > 0.2, these significant associations were binned into 40 quantitative trait loci (QTL) clusters. Among them, 14 important QTL clusters were discovered in two environments and/or with phenotypic contributions greater than 10%. By analyzing the genomic regions within 100 kb upstream and downstream of the peak SNPs within the 14 loci, 334 annotated genes were found. Among these, 32 genes were potentially associated with root development according to their expression analysis. Furthermore, the protein interaction network using the 334 annotated genes gave nine genes involved in a substantial number of interactions, including a key gene associated with root development, BnaC09g36350D. This research provides the groundwork for deciphering B. napus’ genetic variations and improving its root system architecture.

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Genetic variant effects on gene expression in human pancreatic islets and their implications for T2D

Nature Communications ◽

10.1038/s41467-020-18581-8 ◽

2020 ◽

Vol 11 (1) ◽

Cited By ~ 6

Author(s):

Ana Viñuela ◽

Arushi Varshney ◽

Martijn van de Bunt ◽

Rashmi B. Prasad ◽

Olof Asplund ◽

...

Keyword(s):

Large Scale ◽

Association Studies ◽

Cell Types ◽

Genome Wide Association ◽

Regulatory Sequences ◽

Genome Wide Association Studies ◽

Risk Variants ◽

Genome Wide ◽

Gwas Signal ◽

Using Data

Abstract Most signals detected by genome-wide association studies map to non-coding sequence and their tissue-specific effects influence transcriptional regulation. However, key tissues and cell-types required for functional inference are absent from large-scale resources. Here we explore the relationship between genetic variants influencing predisposition to type 2 diabetes (T2D) and related glycemic traits, and human pancreatic islet transcription using data from 420 donors. We find: (a) 7741 cis-eQTLs in islets with a replication rate across 44 GTEx tissues between 40% and 73%; (b) marked overlap between islet cis-eQTL signals and active regulatory sequences in islets, with reduced eQTL effect size observed in the stretch enhancers most strongly implicated in GWAS signal location; (c) enrichment of islet cis-eQTL signals with T2D risk variants identified in genome-wide association studies; and (d) colocalization between 47 islet cis-eQTLs and variants influencing T2D or glycemic traits, including DGKB and TCF7L2. Our findings illustrate the advantages of performing functional and regulatory studies in disease relevant tissues.

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Abstract 1444: Weighted Gene Co-expression Network Analysis of Adipose and Liver Reveals Gene Modules Related to Plasma HDL Levels and Containing Candidate Genes at Loci Identified in Genome Wide Association Studies

Circulation ◽

10.1161/circ.118.suppl_18.s_327 ◽

2008 ◽

Vol 118 (suppl_18) ◽

Author(s):

Peter Langfelder ◽

Margarete Mehrabian ◽

Eric E Schadt ◽

Aldons J Lusis ◽

Steve Horvath

Keyword(s):

Network Analysis ◽

Association Studies ◽

Expression Patterns ◽

Screening Method ◽

Functional Enrichment ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Genome Wide ◽

Gene Modules ◽

Hdl Metabolism

The genetic and environmental factors contributing to HDL-cholesterol levels are highly complex. For example, a recent meta-analysis of three genome wide association studies (GWAS), consisting of over 9000 individuals, revealed several loci, but altogether these explained less than 10% of HDL variation. Since HDL has a heritability of about 50%, there clearly must be many as yet unidentified factors. To better address this complexity, we have utilized integrative genomic approaches to relate common DNA variation to gene networks and HDL metabolism. We report a Weighted Gene Co-expression Network Analysis (WGCNA) of genome-wide expression data from a CAST X C57BL6/J F2 intercross. WGCNA is a systems-based gene expression analysis and gene screening method. It utilizes co-expression patterns among genes to identify gene modules (groups of highly co-expressed genes) significantly associated with a clinical trait, in this case plasma HDL levels. Co-expression modules may represent cellular processes and interacting pathways that provide a bridge between individual genes and a systems-level view of the organism. A module-centric analysis effectively alleviates the multiple testing problems inherent in microarray data analysis and can be considered a biologically motivated data-reduction scheme. Using data from liver and adipose tissues, we have identified several modules strongly associated with plasma HDL levels (p-values ranging from below 1e-20 to 1e-5). Gene ontology and functional enrichment analysis indicate that these modules are indeed biologically meaningful. The modules contain variants of several genes under loci that were recently implicated by three GWA studies: liver modules include GCKR, ANGPTL4, ABCA3, APOA1, and APOA4, while the adipose modules include ABCA6, ANGPTL11 and 12, MMAB, MLXIPL, SORT1, PBX4, PLTP, and APOL6. Thus, our study also serves to help identify likely candidates from GWAS. In conclusion, applying WGCNA methods reveals modules that are biologically meaningful, statistically significant, and enriched for genes and pathways related to HDL metabolism and transport.

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