scholarly journals Mendelian randomization analysis identified genes potentially pleiotropically associated with periodontitis

2021 ◽  
Author(s):  
Feng Wang ◽  
Di Liu ◽  
Yong Zhuang ◽  
Bowen Feng ◽  
Wenjin Lu ◽  
...  
Keyword(s):  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
East Asian ◽  
European Ancestry ◽  
Asian Ancestry ◽  
Multiple Genes ◽  
Genome Wide ◽  
Eqtl Data ◽  
Summary Data ◽  
East Asian Ancestry

AbstractObjectiveTo prioritize genes that were pleiotropically or potentially causally associated with periodontitis.MethodsWe applied the summary data-based Mendelian randomization (SMR) method integrating genome-wide association study (GWAS) for periodontitis and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with periodontitis. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately.ResultsWe identified multiple genes showing pleiotropic association with periodontitis in participants of European ancestry and participants of East Asian ancestry. PDCD2 (corresponding probe: ILMN_1758915) was the top hit showing pleotropic association with periodontitis in participants of European ancestry, and BX093763 (corresponding probe: ILMN_1899903) and AC104135.3 (corresponding probe: ENSG00000204792.2) were the top hits in participants of East Asian ancestry using CAGE eQTL data and GTEx eQTL data, respectively.ConclusionWe identified multiple genes that may be involved in the pathogenesis of periodontitis in participants of European ancestry and participants of East Asian ancestry. Our findings provided important leads to a better understanding of the mechanisms underlying periodontitis and revealed potential therapeutic targets for the effective treatment of periodontitis.

scholarly journals Mendelian randomization analysis identified genes pleiotropically associated with central corneal thickness

BMC Genomics ◽  
2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Zhikun Yang ◽  
Jingyun Yang ◽  
Di Liu ◽  
Weihong Yu
Keyword(s):  
Multiple Testing ◽  
Central Corneal Thickness ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Open Angle Glaucoma ◽  
East Asian ◽  
Corneal Thickness ◽  
European Ancestry ◽  
Genome Wide ◽  
Eqtl Data

Abstract Objective To prioritize genes that were pleiotropically or potentially causally associated with central corneal thickness (CCT). Methods We applied the summary data-based Mendelian randomization (SMR) method integrating summarized data of genome-wide association study (GWAS) on CCT and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with CCT. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analyses were done for participants of European and East Asian ancestries, separately. Results We identified multiple genes showing pleiotropic association with CCT in the participants of European ancestry. CLIC3 (ILMN_1796423; PSMR = 4.15 × 10− 12), PTGDS (ILMN_1664464; PSMR = 6.88 × 10− 9) and C9orf142 (ILMN_1761138; PSMR = 8.09 × 10− 9) were the top three genes using the CAGE eQTL data, and RP11-458F8.4 (ENSG00000273142.1; PSMR = 5.89 × 10− 9), LCNL1 (ENSG00000214402.6; PSMR = 5.67 × 10− 8), and PTGDS (ENSG00000107317.7; PSMR = 1.92 × 10− 7) were the top three genes using the GTEx eQTL data. No genes showed significantly pleiotropic association with CCT in the participants of East Asian ancestry after correction for multiple testing. Conclusion We identified several genes pleiotropically associated with CCT, some of which represented novel genes influencing CCT. Our findings provided important leads to a better understanding of the genetic factors influencing CCT, and revealed potential therapeutic targets for the treatment of primary open-angle glaucoma and keratoconus.

scholarly journals Mendelian randomization analysis identified genes pleiotropically associated with central corneal thickness

2021 ◽  
Author(s):  
Zhikun Yang ◽  
Jingyun Yang ◽  
Di Liu ◽  
Weihong Yu
Keyword(s):  
Multiple Testing ◽  
Central Corneal Thickness ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
Open Angle Glaucoma ◽  
East Asian ◽  
Corneal Thickness ◽  
European Ancestry ◽  
Genome Wide ◽  
Eqtl Data

AbstractObjectiveTo prioritize genes that were pleiotropically or potentially causally associated with central corneal thickness (CCT).MethodsWe applied the summary data-based Mendelian randomization (SMR) method integrating summarized data of genome-wide association study (GWAS) on CCT and expression quantitative trait loci (eQTL) data to identify genes that were pleiotropically associated with CCT. We performed separate SMR analysis using CAGE eQTL data and GTEx eQTL data. SMR analysis were done for participants of European and East Asian ancestries, separately.ResultsWe identified multiple genes showing pleiotropic association with CCT in the participants of European ancestry. CLIC3 (ILMN_1796423; PSMR=4.15×10−12), PTGDS (ILMN_1664464; PSMR=6.88×10−9) and C9orf142 (ILMN_1761138; PSMR=8.09×10−9) were the top three genes using the CAGE eQTL data, and RP11-458F8.4(ENSG00000273142.1; PSMR=5.89×10−9), LCNL1 (ENSG00000214402.6; PSMR=5.67×10−8), and PTGDS (ENSG00000107317.7; PSMR=1.92×10−7) were the top three genes using the GTEx eQTL data. No genes showed significantly pleiotropic association with CCT in the participants of East Asian ancestry after correction for multiple testing.ConclusionWe identified several genes pleiotropically associated with CCT, some of which represented novel genes influencing CCT. Our findings provided important leads to a better understanding of the genetic factors influencing CCT, and revealed potential therapeutic targets for the treatment of primary open-angle glaucoma and keratoconus.

scholarly journals Genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry

PeerJ ◽  
2017 ◽  
Vol 5 ◽  
pp. e3951 ◽  
Author(s):  
Lida Rawofi ◽  
Melissa Edwards ◽  
S Krithika ◽  
Phuong Le ◽  
David Cha ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
East Asian ◽  
Skin Pigmentation ◽  
Genome Wide Association ◽  
Asian Populations ◽  
Iris Color ◽  
Asian Ancestry ◽  
Genome Wide ◽  
East Asian Ancestry

Background Currently, there is limited knowledge about the genetics underlying pigmentary traits in East Asian populations. Here, we report the results of the first genome-wide association study of pigmentary traits (skin and iris color) in individuals of East Asian ancestry. Methods We obtained quantitative skin pigmentation measures (M-index) in the inner upper arm of the participants using a portable reflectometer (N = 305). Quantitative measures of iris color (expressed as L*, a* and b* CIELab coordinates) were extracted from high-resolution iris pictures (N = 342). We also measured the color differences between the pupillary and ciliary regions of the iris (e.g., iris heterochromia). DNA samples were genotyped with Illumina’s Infinium Multi-Ethnic Global Array (MEGA) and imputed using the 1000 Genomes Phase 3 samples as reference haplotypes. Results For skin pigmentation, we did not observe any genome-wide significant signal. We followed-up in three independent Chinese samples the lead SNPs of five regions showing multiple common markers (minor allele frequency ≥ 5%) with good imputation scores and suggestive evidence of association (p-values < 10−5). One of these markers, rs2373391, which is located in an intron of the ZNF804B gene on chromosome 7, was replicated in one of the Chinese samples (p = 0.003). For iris color, we observed genome-wide signals in the OCA2 region on chromosome 15. This signal is driven by the non-synonymous rs1800414 variant, which explains 11.9%, 10.4% and 6% of the variation observed in the b*, a* and L* coordinates in our sample, respectively. However, the OCA2 region was not associated with iris heterochromia. Discussion Additional genome-wide association studies in East Asian samples will be necessary to further disentangle the genetic architecture of pigmentary traits in East Asian populations.

scholarly journals A causal association between schizophrenia and bipolar disorder on rheumatoid arthritis: A two-sample Mendelian randomization study

2021 ◽  
Author(s):  
Gonul Hazal Koc ◽  
Fatih Ozel ◽  
Kaan Okay ◽  
Dogukan Koc
Keyword(s):  
Rheumatoid Arthritis ◽  
Bipolar Disorder ◽  
Genome Wide Association Study ◽  
Mendelian Randomization ◽  
European Ancestry ◽  
Nucleotide Polymorphisms ◽  
Causal Association ◽  
Genome Wide ◽  
Inverse Variance ◽  
Weighted Median

Background: Schizophrenia(SCZ) and bipolar disorder(BD) are both associated with several autoimmune/inflammatory disorders including rheumatoid arthritis(RA). However, a causal association of SCZ and BD on RA is controversial and elusive. In the present study, we aimed to investigate the causal association of SCZ and BD with RA by using the Mendelian randomization (MR) approach. Methods: A two-sample MR(2SMR) study including the inverse-variance weighted(IVW), weighted median, simple mode, weighted mode and MR-Egger methods were performed. We employed summary-level genome-wide association study(GWAS) data including BD and SCZ as exposure and RA as an outcome. We utilized data from the Psychiatric Genomics Consortium(PGC) for BD(n= 41,917) and SCZ(n= 33,426), whereas RA GWAS dataset (58,284 individuals) from the European ancestry. Results: We obtained independent (r2 <0.001) 48 and 52 single nucleotide polymorphisms (SNPs) from BD and SCZ data at genome-wide significance (p <5x10-8), respectively. Next, these SNPs were utilized as instrumental variables(IVs) in 2SMR analysis to explore the causality of BD and SCZ on RA. The two out of five MR methods showed a statistically significant inverse causal association between BD and RA: weighted median method(odds ratio (OR), 0.869, [95% CI, 0.764-0.989]; P= 0.034) and inverse-variance weighted(IVW) method (OR, 0.810, [95% CI, 0.689-0.953]; P= 0.011). However, we did not find any significant association of SCZ with RA (OR, 1.008, [95% CI, 0.931-1.092]; P= 0.829, using the IVW method). Conclusions: These results provide support for an inverse causal association between BD and RA. Further investigation is needed to explain the underlying protective mechanisms in the development of RA.

scholarly journals Multi-Ancestry Meta-Analysis yields novel genetic discoveries and ancestry-specific associations

2021 ◽  
Author(s):  
Patrick Turley ◽  
Alicia R. Martin ◽  
Grant Goldman ◽  
Hui Li ◽  
Masahiro Kanai ◽  
...  
Keyword(s):  
Error Rate ◽  
Genome Wide Association Study ◽  
Meta Analysis ◽  
East Asian ◽  
Genome Wide Association ◽  
European Ancestry ◽  
Summary Statistics ◽  
Type 1 Error ◽  
Genome Wide

ABSTRACTWe present a new method, Multi-Ancestry Meta-Analysis (MAMA), which combines genome-wide association study (GWAS) summary statistics from multiple populations to produce new summary statistics for each population, identifying novel loci that would not have been discovered in either set of GWAS summary statistics alone. In simulations, MAMA increases power with less bias and generally lower type-1 error rate than other multi-ancestry meta-analysis approaches. We apply MAMA to 23 phenotypes in East-Asian- and European-ancestry populations and find substantial gains in power. In an independent sample, novel genetic discoveries from MAMA replicate strongly.

scholarly journals Trans-ethnic Mendelian randomization study reveals causal relationships between cardio-metabolic factors and chronic kidney disease

2020 ◽  
Author(s):  
Jie Zheng ◽  
Yuemiao Zhang ◽  
Humaira Rasheed ◽  
Venexia Walker ◽  
Yuka Sugawara ◽  
...  
Keyword(s):  
Risk Factors ◽  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Mendelian Randomization ◽  
East Asian ◽  
Causal Effects ◽  
European Ancestry ◽  
East Asians ◽  
East Asian Ancestry

BACKGROUND The chronic kidney disease (CKD) public health burden is substantial and has not declined as expected with current interventions on disease treatments. A large number of clinical, biological, and behavioural risk factors have been associated with CKD. However, it is unclear which of them are causal. OBJECTIVE To systematically test whether previously reported risk factors for CKD are causally related to the disease in European and East Asian ancestries. DESIGN Two-sample Mendelian randomization (MR) and non-linear MR analyses. PARTICIPANTS 53,703 CKD cases and 960,624 controls of European ancestry from CKDGen, UK Biobank and HUNT, and 13,480 CKD cases and 238,118 controls of East Asian ancestry from Biobank Japan, China Kadoorie Biobank and Japan-Kidney-Biobank/ToMMo. MEASURES Systematic literature mining of PubMed studies identified 45 clinical risk factors and biomarkers with robustly associated genetic variants, including phenotypes related to blood pressure, diabetes, glucose, insulin, lipids, obesity, smoking, sleep disorders, nephrolithiasis, uric acid, coronary artery disease, bone mineral density, homocysteine, C-reactive protein, micro-nutrients and thyroid function, which were selected as exposures. The outcome was CKD (defined by clinical diagnosis or by estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2). RESULTS Eight risk factors showed evidence of causal effects on CKD in European ancestry, including body mass index (BMI), hypertension, systolic blood pressure, high density lipoprotein cholesterol, apolipoprotein A-I, lipoprotein A, type 2 diabetes (T2D) and nephrolithiasis. In East Asian ancestry, BMI, T2D and nephrolithiasis showed evidence of causal effects on CKD. Hypertension showed reliable evidence of a strong causal effect on CKD in Europeans but in contrast appeared to show a null effect in East Asians, suggesting the possibility of different causal risk factors in Europeans and East Asians. Although liability to T2D showed consistent effects on CKD, the effect of glycemic traits on CKD was weak, suggesting T2D may have glucose-independent mechanisms to influence CKD. Non-linear MR indicated a threshold relationship between genetically predicted BMI and CKD, with increased risk at BMI above 25 kg/m2. LIMITATION Due to the unbalanced distribution of data between ancestries, we could only test 17 of the 45 risk factors in East Asian participants. CONCLUSIONS Eight CKD-associated risk factors showed evidence of causal effects on the disease in over 1.2 million European and East Asian ancestries. These risk factors were predominantly related to cardio-metabolic health, which supports the shared causal link between cardio-metabolic health and kidney function. This study provides evidence of potential intervention targets for primary prevention of CKD, which could help reduce the global burden of CKD and its cardio-metabolic co-morbidities.

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