Genome-Wide Association Study Demonstrates the Role Played by the CD226 Gene in Rasa Aragonesa Sheep Reproductive Seasonality

A genome-wide association study (GWAS) was used to identify genomic regions influencing seasonality reproduction traits in Rasa Aragonesa sheep. Three traits associated with either ovarian function based on blood progesterone levels (total days of anoestrus and progesterone cycling months) or behavioral signs of oestrous (oestrous cycling months) were studied. The GWAS included 205 ewes genotyped using the 50k and 680k Illumina Ovine Beadchips. Only one SNP associated with the progesterone cycling months overcame the genome-wide significance level (rs404991855). Nine SNPs exhibited significant associations at the chromosome level, being the SNPs rs404991855 and rs418191944, that are located in the CD226 molecule (CD226) gene, associated with the three traits. This gene is related to reproductive diseases. Two other SNPs were located close to the neuropeptide Y (NPY) gene, which is involved in circadian rhythms. To validate the GWAS, partial characterization of both genes by Sanger sequencing, and genotyping of two synonymous and two nonsynonymous SNPs in the NPY and CD226 genes, respectively, were performed. SNP association analysis showed that only SNP rs404360094 in the exon 3 of the CD226 gene, which produces an amino acid substitution from asparagine (uncharged polar) to aspartic acid (acidic), was associated with the three seasonality traits. Our results suggest that the CD226 gene may be involved in the reproductive seasonality in Rasa Aragonesa.

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Genome-Wide Association Study of Metabolic Syndrome Reveals Primary Genetic Variants at CETP Locus in Indians

Biomolecules ◽

10.3390/biom9080321 ◽

2019 ◽

Vol 9 (8) ◽

pp. 321 ◽

Cited By ~ 3

Author(s):

Gauri Prasad ◽

Khushdeep Bandesh ◽

Anil Giri ◽

Yasmeen Kauser ◽

Prakriti Chanda ◽

...

Keyword(s):

Metabolic Syndrome ◽

Adipose Tissue ◽

Association Study ◽

Genome Wide Association Study ◽

Genome Wide Association ◽

Rapid Urbanization ◽

Significance Level ◽

Genome Wide ◽

A Genome ◽

Replication Phase

Indians, a rapidly growing population, constitute vast genetic heterogeneity to that of Western population; however they have become a sedentary population in past decades due to rapid urbanization ensuing in the amplified prevalence of metabolic syndrome (MetS). We performed a genome-wide association study (GWAS) of MetS in 10,093 Indian individuals (6617 MetS and 3476 controls) of Indo-European origin, that belong to our previous biorepository of The Indian Diabetes Consortium (INDICO). The study was conducted in two stages—discovery phase (N = 2158) and replication phase (N = 7935). We discovered two variants within/near the CETP gene—rs1800775 and rs3816117—associated with MetS at genome-wide significance level during replication phase in Indians. Additional CETP loci rs7205804, rs1532624, rs3764261, rs247617, and rs173539 also cropped up as modest signals in Indians. Haplotype association analysis revealed GCCCAGC as the strongest haplotype within the CETP locus constituting all seven CETP signals. In combined analysis, we perceived a novel and functionally relevant sub-GWAS significant locus—rs16890462 in the vicinity of SFRP1 gene. Overlaying gene regulatory data from ENCODE database revealed that single nucleotide polymorphism (SNP) rs16890462 resides in repressive chromatin in human subcutaneous adipose tissue as characterized by the enrichment of H3K27me3 and CTCF marks (repressive gene marks) and diminished H3K36me3 marks (activation gene marks). The variant displayed active DNA methylation marks in adipose tissue, suggesting its likely regulatory activity. Further, the variant also disrupts a potential binding site of a key transcription factor, NRF2, which is known for involvement in obesity and metabolic syndrome.

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A genome-wide association study of reproduction traits in four pig populations with different genetic backgrounds

Asian-Australasian Journal of Animal Sciences ◽

10.5713/ajas.19.0411 ◽

2020 ◽

Vol 33 (9) ◽

pp. 1400-1410

Author(s):

Yao Jiang ◽

Shaoqing Tang ◽

Wei Xiao ◽

Peng Yun ◽

Xiangdong Ding

Keyword(s):

Association Study ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Genome Wide Association ◽

Nucleotide Polymorphisms ◽

Multiple Trait ◽

Multiple Populations ◽

Genome Wide ◽

A Genome ◽

Reproduction Traits

Objective: Genome-wide association study and two meta-analysis based on GWAS performed to explore the genetic mechanism underlying variation in pig number born alive (NBA) and total number born (TNB).Methods: Single trait GWAS and two meta-analysis (single-trait meta analysis and multitrait meta analysis) were used in our study for NBA and TNB on 3,121 Yorkshires from 4 populations, including three different American Yorkshire populations (n = 2,247) and one British Yorkshire populations (n = 874).Results: The result of single trait GWAS showed that no significant associated single nucleotide polymorphisms (SNPs) were identified. Using single-trait meta analysis and multi-trait meta analysis within populations, 11 significant loci were identified associated with target traits. Spindlin 1, vascular endothelial growth factor A, forkhead box Q1, msh homeobox 1, and LHFPL tetraspan submily member 3 are five functionally plausible candidate genes for NBA and TNB. Compared to the single population GWAS, single-trait Meta analysis can improve the detection power to identify SNPs by integrating information of multiple populations. The multiple-trait analysis reduced the power to detect trait-specific loci but enhanced the power to identify the common loci across traits.Conclusion: In total, our findings identified novel genes to be validated as candidates for NBA and TNB in pigs. Also, it enabled us to enlarge population size by including multiple populations with different genetic backgrounds and increase the power of GWAS by using meta analysis.

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Assessment of rosacea symptom severity by genome-wide association study and expression analysis highlights immuno-inflammatory and skin pigmentation genes

Human Molecular Genetics ◽

10.1093/hmg/ddy184 ◽

2018 ◽

Vol 27 (15) ◽

pp. 2762-2772 ◽

Cited By ~ 9

Author(s):

Jennifer L Aponte ◽

Mathias N Chiano ◽

Laura M Yerges-Armstrong ◽

David A Hinds ◽

Chao Tian ◽

...

Keyword(s):

Association Study ◽

Symptom Severity ◽

Genome Wide Association Study ◽

Skin Pigmentation ◽

Genome Wide Association ◽

European Ancestry ◽

P Value ◽

Significance Level ◽

Genome Wide ◽

A Genome

Abstract Rosacea is a common, chronic skin disease of variable severity with limited treatment options. The cause of rosacea is unknown, but it is believed to be due to a combination of hereditary and environmental factors. Little is known about the genetics of the disease. We performed a genome-wide association study (GWAS) of rosacea symptom severity with data from 73 265 research participants of European ancestry from the 23andMe customer base. Seven loci had variants associated with rosacea at the genome-wide significance level (P < 5 × 10−8). Further analyses highlighted likely gene regions or effector genes including IRF4 (P = 1.5 × 10−17), a human leukocyte antigen (HLA) region flanked by PSMB9 and HLA-DMB (P = 2.2 × 10−15), HERC2-OCA2 (P = 4.2 × 10−12), SLC45A2 (P = 1.7 × 10−10), IL13 (P = 2.8 × 10−9), a region flanked by NRXN3 and DIO2 (P = 4.1 × 10−9), and a region flanked by OVOL1and SNX32 (P = 1.2 × 10−8). All associations with rosacea were novel except for the HLA locus. Two of these loci (HERC-OCA2 and SLC45A2) and another precedented variant (rs1805007 in melanocortin 1 receptor) with an association P value just below the significance threshold (P = 1.3 × 10−7) have been previously associated with skin phenotypes and pigmentation, two of these loci are linked to immuno-inflammation phenotypes (IL13 and PSMB9-HLA-DMA) and one has been associated with both categories (IRF4). Genes within three loci (PSMB9-HLA-DMA, HERC-OCA2 and NRX3-DIO2) were differentially expressed in a previously published clinical rosacea transcriptomics study that compared lesional to non-lesional samples. The identified loci provide specificity of inflammatory mechanisms in rosacea, and identify potential pathways for therapeutic intervention.

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Genetic risk of clozapine-induced leukopenia and neutropenia: a genome-wide association study

Translational Psychiatry ◽

10.1038/s41398-021-01470-z ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jianhua Chen ◽

Ping Yang ◽

Qian Zhang ◽

Ruirui Chen ◽

Peng Wang ◽

...

Keyword(s):

Association Study ◽

Molecular Mechanisms ◽

Genome Wide Association Study ◽

Meta Analysis ◽

Genome Wide Association ◽

Nucleotide Polymorphisms ◽

Significance Level ◽

Genome Wide ◽

A Genome ◽

Genome Wide Significance

Abstract Background Clozapine is considered to be the most effective antipsychotic medication for schizophrenia. However, it is associated with several adverse effects such as leukopenia, and the underlying mechanism has not yet been fully elucidated. The authors performed a genome-wide association study (GWAS) in a Chinese population to identify genetic markers for clozapine-induced leukopenia (CIL) and clozapine-induced neutropenia (CIN). Methods A total of 1879 patients (225 CIL cases, including 43 CIN cases, and 1,654 controls) of Chinese descent were included. Data from common and rare single nucleotide polymorphisms (SNPs) were tested for association. The authors also performed a trans-ancestry meta-analysis with GWAS results of European individuals from the Clozapine-Induced Agranulocytosis Consortium (CIAC). Results The authors identified several novel loci reaching the threshold of genome-wide significance level (P < 5 × 10−8). Three novel loci were associated with CIL while six were associated with CIN, and two T cell related genes (TRAC and TRAT1) were implicated. The authors also observed that one locus with evidence close to genome-wide significance (P = 5.08 × 10−8) was near the HLA-B gene in the major histocompatibility complex region in the trans-ancestry meta-analysis. Conclusions The associations provide novel and valuable understanding of the genetic and immune causes of CIL and CIN, which is useful for improving clinical management of clozapine related treatment for schizophrenia. Causal variants and related underlying molecular mechanisms need to be understood in future developments.

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