Fine mapping genetic variants associated with age at puberty and sow fertility using SowPro90 genotyping array

Abstract Sow fertility traits, such as litter size and the number of lifetime parities produced (reproductive longevity), are economically important. Selection for these traits is difficult because they are lowly heritable and expressed late in life. Age at puberty (AP) is an early indicator of reproductive longevity. Here, we utilized a custom Affymetrix single-nucleotide polymorphisms (SNPs) array (SowPro90) enriched with positional candidate genetic variants for AP and a haplotype-based genome-wide association study to fine map the genetic sources associated with AP and other fertility traits in research (University of Nebraska-Lincoln [UNL]) and commercial sow populations. Five major quantitative trait loci (QTL) located on four Sus scrofa chromosomes (SSC2, SSC7, SSC14, and SSC18) were discovered for AP in the UNL population. Negative correlations (r = −0.96 to −0.10; P < 0.0001) were observed at each QTL between genomic estimated breeding values for AP and reproductive longevity measured as lifetime number of parities (LTNP). Some of the SNPs discovered in the major QTL regions for AP were located in candidate genes with fertility-associated gene ontologies (e.g., P2RX3, NR2F2, OAS1, and PTPN11). These SNPs showed significant (P < 0.05) or suggestive (P < 0.15) associations with AP, reproductive longevity, and litter size traits in the UNL population and litter size traits in the commercial sows. For example, in the UNL population, when the number of favorable alleles of an SNP located in the 3′ untranslated region of PTPN11 (SSC14) increased, AP decreased (P < 0.0001), while LTNP increased (P < 0.10). Additionally, a suggestive difference in the observed NR2F2 isoforms usage was hypothesized to be the source of the QTL for puberty onset mapped on SSC7. It will be beneficial to further characterize these candidate SNPs and genes to understand their impact on protein sequence and function, gene expression, splicing process, and how these changes affect the phenotypic variation of fertility traits.

Download Full-text

Lifestyle factors and genetic variants on two biological age measures: evidence from 94,443 Taiwan Biobank participants

The Journals of Gerontology Series A ◽

10.1093/gerona/glab251 ◽

2021 ◽

Author(s):

Wan-Yu Lin

Keyword(s):

Genetic Variants ◽

Genome Wide Association Study ◽

Lifestyle Factors ◽

Biological Age ◽

Biological Aging ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Genome Wide ◽

A Genome ◽

The Uk

Abstract Background Biological age (BA) can be estimated by phenotypes and is useful for predicting lifespan and healthspan. Levine et al. proposed a PhenoAge and a BioAge to measure BA. Although there have been studies investigating the genetic predisposition to BA acceleration in Europeans, little has been known regarding this topic in Asians. Methods I here estimated PhenoAgeAccel (age-adjusted PhenoAge) and BioAgeAccel (age-adjusted BioAge) of 94,443 Taiwan Biobank (TWB) participants, wherein 25,460 TWB1 subjects formed a discovery cohort and 68,983 TWB2 individuals constructed a replication cohort. Lifestyle factors and genetic variants associated with PhenoAgeAccel and BioAgeAccel were investigated through regression analysis and a genome-wide association study (GWAS). Results A unit (kg/m 2) increase of BMI was associated with a 0.177-year PhenoAgeAccel (95% C.I. = 0.163~0.191, p = 6.0×) and 0.171-year BioAgeAccel (95% C.I. = 0.165~0.177, p = 0). Smokers on average had a 1.134-year PhenoAgeAccel (95% C.I. = 0.966~1.303, p = 1.3×) compared with non-smokers. Drinkers on average had a 0.640-year PhenoAgeAccel (95% C.I. = 0.433~0.847, p = 1.3×) and 0.193-year BioAgeAccel (95% C.I. = 0.107~0.279, p = 1.1×) relative to non-drinkers. A total of 11 and 4 single-nucleotide polymorphisms (SNPs) were associated with PhenoAgeAccel and BioAgeAccel (p<5× in both TWB1 and TWB2), respectively. Conclusions A PhenoAgeAccel-associated SNP (rs1260326 in GCKR) and two BioAgeAccel-associated SNPs (rs7412 in APOE; rs16998073 near FGF5) were consistent with the finding from the UK Biobank. The lifestyle analysis shows that prevention from obesity, cigarette smoking, and alcohol consumption is associated with a slower rate of biological aging.

Download Full-text

GWAS of Post-Orthodontic Aggressive External Apical Root Resorption Identified Multiple Putative Loci at X-Y Chromosomes

Journal of Personalized Medicine ◽

10.3390/jpm10040169 ◽

2020 ◽

Vol 10 (4) ◽

pp. 169

Author(s):

Paula Iber-Díaz ◽

Raquel Senen-Carramolino ◽

Alejandro Iglesias-Linares ◽

Pablo Fernández-Navarro ◽

Carlos Flores-Mir ◽

...

Keyword(s):

Logistic Regression ◽

Genetic Variants ◽

Genome Wide Association Study ◽

Root Resorption ◽

Genetic Model ◽

Nucleotide Polymorphisms ◽

Apical Root Resorption ◽

A Genome ◽

Increased Risk ◽

External Apical Root Resorption

Personalized dental medicine requires from precise and customized genomic diagnostic. To conduct an association analysis over multiple putative loci and genes located at chromosomes 2, 4, 8, 12, 18, X, and Y, potentially implicated in an extreme type of external apical root resorption secondary to orthodontic forces (aEARR). A genome-wide association study of aEARR was conducted with 480 patients [ratio~1:3 case/control]. Genomic DNA was extracted and analyzed using the high-throughput Axiom platform with the GeneTitan® MC Instrument. Up to 14,377 single nucleotide polymorphisms (SNPs) were selected at candidate regions and clinical/diagnostic data were recorded. A descriptive analysis of the data along with a backward conditional binary logistic regression was used to calculate odds ratios, with 95% confidence intervals [p < 0.05]. To select the best SNP candidates, a logistic regression model was fitted assuming a log-additive genetic model using R software [p < 0.0001]. In this sample the top lead genetic variants associated with aEARR were two novel putative genes located in the X chromosome, specifically, STAG 2 gene, rs151184635 and RP1-30E17.2 gene, rs55839915. These variants were found to be associated with an increased risk of aEARR, particularly restricted to men [OR: 6.09; 95%CI: 2.6–14.23 and OR: 6.86; 95%CI: 2.65–17.81, respectively]. Marginal associations were found at previously studied variants such as SSP1: rs11730582 [OR: 0.54; 95%CI: 0.34–0.86; p = 0.008], P2RX7: rs1718119 [OR: 0.6; 95%CI: 0.36–1.01; p = 0.047], and TNFRSF11A: rs8086340 [OR: 0.6; 95%CI: 0.38–0.95; p = 0.024]), found solely in females. Multiple putative genetic variants located at chromosomes X and Y are potentially implicated in an extreme phenotype of aEARR. A gender-linked association was noted.

Download Full-text

Association between Ocular Axial Length-Related Genes and High Myopia in a Han Chinese Population

Ophthalmologica ◽

10.1159/000439446 ◽

2015 ◽

Vol 235 (1) ◽

pp. 57-60 ◽

Cited By ~ 10

Author(s):

Ya-Ting Li ◽

Ming-Kun Xie ◽

Jin Wu

Keyword(s):

Axial Length ◽

Genetic Variants ◽

Chinese Population ◽

High Myopia ◽

Genome Wide Association Study ◽

Han Chinese ◽

Nucleotide Polymorphisms ◽

Han Chinese Population ◽

Functional Roles ◽

Genome Wide

Aims: A previous genome-wide association study of high myopia identified five genome-wide loci for ocular axial length (C3orf26, ZC3H11B, RSPO1, GJD2, and ZNRF3). The aim of our study was to investigate the association between high myopia and genetic variants in the five loci in Han Chinese subjects. Methods: Five single nucleotide polymorphisms were genotyped in 296 unrelated high-myopia subjects and 300 matched emmetropic controls by the SNaPshot method. The distribution of genotypes in the cases and controls was compared in codominant, dominant, and recessive genetic models by using SNPStats online software. Results: Significant associations between rs994767 near ZC3H11B (p = 0.001), rs4074961 in RSPO1 (p < 0.001), and rs11073058 in GJD2 (p = 0.029) and high myopia were observed. Odds ratios (95% confidence intervals) were 1.532 (1.200-1.955), 1.603 (1.267-2.029), and 1.290 (1.027-1.621) for the rs994767 T allele, rs4074961 T allele, and rs11073058 T allele, respectively. But rs9811920 in C3orf26 and rs12321 in ZNRF3 were not associated with high myopia. Conclusion: Our findings suggested that genetic variants in ZC3H11B, RSPO1, and GJD2 are associated with susceptibility to the development of high myopia in a Han Chinese population. Functional roles of ZC3H11B, RSPO1, and GJD2 in the pathology of high myopia need to be further investigated.

Download Full-text

SNPs and GVHD prediction: where to next?

Blood ◽

10.1182/blood-2012-03-409078 ◽

2012 ◽

Vol 119 (22) ◽

pp. 5066-5068 ◽

Cited By ~ 6

Author(s):

Anne M. Dickinson

Keyword(s):

Genome Wide Association Study ◽

Snp Array ◽

Candidate Snps ◽

Cell Transplant ◽

Nucleotide Polymorphisms ◽

Hematopoietic Stem ◽

Novel Approach ◽

Genome Wide ◽

Impute Data ◽

A Genome

The article by Chien at al in this issue of Blood uses a novel approach to assess the role of single nucleotide polymorphisms (SNPs) in acute graft-versus-host disease (GVHD). Using a genome-wide association study (GWAS) employing an Affymetrix GeneChip Genome-Wide Human 500 000 SNP array, they screened 1298 allogeneic hematopoietic stem cell transplant donors and recipients and tested whether the results from 40 previously reported candidate SNPs could be replicated. They also used a novel approach to impute data using IMPUTE software (http://nathgen.stats-ox.ac.uk/impute/impute.html) where the genotyping data were not available.1

Download Full-text

A Genome-Wide Association Study of Novel Genetic Variants Associated With Anthropometric Traits in Koreans

Frontiers in Genetics ◽

10.3389/fgene.2021.669215 ◽

2021 ◽

Vol 12 ◽

Author(s):

Hye-Won Cho ◽

Hyun-Seok Jin ◽

Yong-Bin Eom

Keyword(s):

Genetic Variants ◽

Genetic Factors ◽

Genome Wide Association Study ◽

Association Studies ◽

Fat Distribution ◽

Genome Wide Association ◽

Genome Wide Association Studies ◽

Nucleotide Polymorphisms ◽

Genome Wide ◽

A Genome

Most previous genome-wide association studies (GWAS) have identified genetic variants associated with anthropometric traits. However, most of the evidence were reported in European populations. Anthropometric traits such as height and body fat distribution are significantly affected by gender and genetic factors. Here we performed GWAS involving 64,193 Koreans to identify the genetic factors associated with anthropometric phenotypes including height, weight, body mass index, waist circumference, hip circumference, and waist-to-hip ratio. We found nine novel single-nucleotide polymorphisms (SNPs) and 59 independent genetic signals in genomic regions that were reported previously. Of the 19 SNPs reported previously, eight genetic variants at RP11-513I15.6 and one genetic variant at the RP11-977G19.10 region and six Asian-specific genetic variants were newly found. We compared our findings with those of previous studies in other populations. Five overlapping genetic regions (PAN2, ANKRD52, RNF41, HGMA1, and C6orf106) had been reported previously but none of the SNPs were independently identified in the current study. Seven of the nine newly found novel loci associated with height in women revealed a statistically significant skeletal expression of quantitative trait loci. Our study provides additional insight into the genetic effects of anthropometric phenotypes in East Asians.

Download Full-text

Association of common genetic variants in the CPSF7 and SDHAF2 genes with Canine Idiopathic Pulmonary Fibrosis in the West Highland White Terrier

10.1101/2020.04.14.030486 ◽

2020 ◽

Author(s):

Ignazio S. Piras ◽

Christiane Bleul ◽

Ashley Siniard ◽

Amanda J. Wolfe ◽

Matthew D. De Both ◽

...

Keyword(s):

Idiopathic Pulmonary Fibrosis ◽

Pulmonary Fibrosis ◽

Genetic Variants ◽

Genome Wide Association Study ◽

Nucleotide Polymorphisms ◽

The West ◽

Genome Wide ◽

Common Genetic Variants ◽

A Genome ◽

Fibrotic Lung Disease

AbstractCanine Idiopathic Pulmonary Fibrosis (CIPF) is a chronic fibrotic lung disease that is observed at a higher frequency in the West Highland White Terrier dog breed (WHWT) and may have molecular pathological overlap with human lung fibrotic disease. We conducted a Genome-Wide Association Study (GWAS) in the WHWT using Whole Genome Sequencing (WGS) to discover genetic variants associated with CIPF. Saliva-derived DNA samples were sequenced using the Riptide™ DNA library prep kit. After quality controls, 28 affected, 44 unaffected and 1,843,695 informative Single Nucleotide Polymorphisms (SNPs) were included in the GWAS. Data were analyzed both at the single SNP and gene levels using the GEMMA and GATES methods, respectively. We detected significant signals at the gene level in both the CPSF7 and SDHAF2 genes (adjusted p = 0.016 and p = 0.025, respectively), two overlapping genes located on chromosome 18. The top SNP for both genes was rs22669389, however it did not reach genome-wide significance in the GWAS (adjusted p = 0.078). Our studies provide, for the first time, candidate loci for CIPF in the WHWT. CPSF7 was recently associated with lung adenocarcinoma further highlighting the potential relevance of our results since IPF and lung cancer share several pathological mechanisms.

Download Full-text

Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study

10.21203/rs.3.rs-21047/v4 ◽

2020 ◽

Author(s):

Shigekazu Sugino ◽

Daisuke Konno ◽

Yosuke Kawai ◽

Masao Nagasaki ◽

Yasuhiro Endo ◽

...

Keyword(s):

Postoperative Nausea ◽

Genome Wide Association Study ◽

Postoperative Nausea And Vomiting ◽

Nausea And Vomiting ◽

Candidate Snps ◽

Nucleotide Polymorphisms ◽

Non Coding Rna ◽

Genome Wide ◽

A Genome ◽

Long Non Coding Rna

Abstract Background: Genetic factors such as single nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study was to identify SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. Methods: Associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients were assessed using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. Results: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). Conclusions: We identified a novel SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. Trial registration: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903, date of registration: June 27th, 2016, retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026392).

Download Full-text

Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study

Human Genomics ◽

10.1186/s40246-020-00282-4 ◽

2020 ◽

Vol 14 (1) ◽

Author(s):

Shigekazu Sugino ◽

Daisuke Konno ◽

Yosuke Kawai ◽

Masao Nagasaki ◽

Yasuhiro Endo ◽

...

Keyword(s):

Postoperative Nausea ◽

Genome Wide Association Study ◽

Postoperative Nausea And Vomiting ◽

Nausea And Vomiting ◽

Candidate Snps ◽

Nucleotide Polymorphisms ◽

Non Coding Rna ◽

Genome Wide ◽

A Genome ◽

Long Non Coding Rna

Abstract Background Genetic factors such as single-nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study was to identify SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. Methods Associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients were assessed using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. Results The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). Conclusions We identified a novel SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. Trial registration This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903, date of registration: June 27, 2016, retrospectively registered.

Download Full-text

Systematic evaluation of the effects of genetic variants on PIWI-interacting RNA expression across 33 cancer types

Nucleic Acids Research ◽

10.1093/nar/gkaa1190 ◽

2020 ◽

Author(s):

Junyi Xin ◽

Mulong Du ◽

Xia Jiang ◽

Yanling Wu ◽

Shuai Ben ◽

...

Keyword(s):

Genetic Variants ◽

Genome Wide Association Study ◽

The Cancer Genome Atlas ◽

Systematic Evaluation ◽

Eqtl Analysis ◽

Nucleotide Polymorphisms ◽

Cancer Etiology ◽

Functional Roles ◽

Cancer Types ◽

Trait Locus

Abstract PIWI-interacting RNAs (piRNAs) are an emerging class of non-coding RNAs involved in tumorigenesis. Expression quantitative trait locus (eQTL) analysis has been demonstrated to help reveal the genetic mechanism of single nucleotide polymorphisms (SNPs) in cancer etiology. However, there are no databases that have been constructed to provide an eQTL analysis between SNPs and piRNA expression. In this study, we collected genotyping and piRNA expression data for 10 997 samples across 33 cancer types from The Cancer Genome Atlas (TCGA). Using linear regression cis-eQTL analysis with adjustment of appropriate covariates, we identified millions of SNP-piRNA pairs in tumor (76 924 831) and normal (24 431 061) tissues. Further, we performed differential expression and survival analyses, and linked the eQTLs to genome-wide association study (GWAS) data to comprehensively decipher the functional roles of identified cis-piRNA eQTLs. Finally, we developed a user-friendly database, piRNA-eQTL (http://njmu-edu.cn:3838/piRNA-eQTL/), to help users query, browse and download corresponding eQTL results. In summary, piRNA-eQTL could serve as an important resource to assist the research community in understanding the roles of genetic variants and piRNAs in the development of cancers.

Download Full-text

Long non-coding RNA MIR4300HG polymorphisms are associated with postoperative nausea and vomiting: a genome-wide association study

10.21203/rs.3.rs-21047/v2 ◽

2020 ◽

Author(s):

Shigekazu Sugino ◽

Daisuke Konno ◽

Yosuke Kawai ◽

Masao Nagasaki ◽

Yasuhiro Endo ◽

...

Keyword(s):

Postoperative Nausea ◽

Genome Wide Association Study ◽

Postoperative Nausea And Vomiting ◽

Nausea And Vomiting ◽

Candidate Snps ◽

Nucleotide Polymorphisms ◽

Non Coding Rna ◽

Genome Wide ◽

A Genome ◽

Long Non Coding Rna

Abstract Background: Genetic factors such as single nucleotide polymorphisms (SNPs) play a key role in the development of postoperative nausea and vomiting (PONV). However, previous findings are not widely applicable to different populations because of population-specific genetic variation. We developed a Japanese-specific DNA microarray for high-throughput genotyping. The aim of the current study is to identify causal SNPs associated with PONV on a genome-wide scale using this microarray in a sample of Japanese surgical patients. associations between 659,636 SNPs and the incidence of PONV 24 h after surgery in a limited sample of 24 female patients using the microarray. After imputation of genotypes at 24,330,529 SNPs, 78 SNPs were found to be associated with the incidence of PONV. We chose 4 of the 78 SNPs to focus on by in silico functional annotation. Finally, we genotyped these 4 candidate SNPs in 255 patients using real-time PCR to verify association with the incidence of PONV. Results: The T > C variant of rs11232965 in the long non-coding RNA MIR4300HG was significantly associated with reduced incidence of PONV among genotypes and between alleles (p = 0.01 and 0.007). Conclusions: We identified a novel causal SNP (rs11232965) in the long non-coding RNA MIR4300HG that is associated with PONV. The rs11232965-SNP variant (T > C) is protective against the incidence of PONV. Trial registration: This study was registered at the UMIN Clinical Trials Registry (Identifier: UMIN000022903, date of registration: June 27th, 2016, retrospectively registered, https://upload.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000026392).

Download Full-text