A genome-wide meta-analysis of genetic variants associated with allergic rhinitis and grass sensitization and their interaction with birth order

Abstract Context Glycated hemoglobin A1c (HbA1c) level is used to screen and diagnose diabetes. Genetic determinants of HbA1c can vary across populations and many of the genetic variants influencing HbA1c level were specific to populations. Objective To discover genetic variants associated with HbA1c level in nondiabetic Malay individuals. Design and Participants We conducted a genome-wide association study (GWAS) analysis for HbA1c using 2 Malay studies, the Singapore Malay Eye Study (SiMES, N = 1721 on GWAS array) and the Living Biobank study (N = 983 on GWAS array and whole-exome sequenced). We built a Malay-specific reference panel to impute ethnic-specific variants and validate the associations with HbA1c at ethnic-specific variants. Results Meta-analysis of the 1000 Genomes imputed array data identified 4 loci at genome-wide significance (P < 5 × 10-8). Of the 4 loci, 3 (ADAM15, LINC02226, JUP) were novel for HbA1c associations. At the previously reported HbA1c locus ATXN7L3-G6PC3, association analysis using the exome data fine-mapped the HbA1c associations to a 27-bp deletion (rs769664228) at SLC4A1 that reduced HbA1c by 0.38 ± 0.06% (P = 3.5 × 10-10). Further imputation of this variant in SiMES confirmed the association with HbA1c at SLC4A1. We also showed that these genetic variants influence HbA1c level independent of glucose level. Conclusion We identified a deletion at SLC4A1 associated with HbA1c in Malay. The nonglycemic lowering of HbA1c at rs769664228 might cause individuals carrying this variant to be underdiagnosed for diabetes or prediabetes when HbA1c is used as the only diagnostic test for diabetes.

Download Full-text

A Genome-wide Association and Admixture Mapping Study of Bronchodilator Drug Response in African Americans with Asthma

10.1101/157198 ◽

2017 ◽

Cited By ~ 1

Author(s):

Melissa L. Spear ◽

Donglei Hu ◽

Maria Pino-Yanes ◽

Scott Huntsman ◽

Anton S. M. Sonnenberg ◽

...

Keyword(s):

African Americans ◽

Genetic Variants ◽

Drug Response ◽

Meta Analysis ◽

Genome Wide ◽

A Genome ◽

Children With Asthma ◽

American Children ◽

Racial Ethnic ◽

Shared Genetic

AbstractBackgroundShort-acting B2-adrenergic receptor agonists (SABAs) are the most commonly prescribed asthma medications worldwide. Response to SABAs is measured as bronchodilator drug response (BDR), which varies among racial/ethnic groups in the U.S 1, 2. However, the genetic variation that contributes to BDR is largely undefined in African Americans with asthma3ObjectiveTo identify genetic variants that may contribute to differences in BDR in African Americans with asthma.MethodsWe performed a genome-wide association study of BDR in 949 African American children with asthma, genotyped with the Axiom World Array 4 (Affymetrix, Santa Clara, CA) followed by imputation using 1000 Genomes phase 3 genotypes. We used linear regression models adjusting for age, sex, body mass index and genetic ancestry to test for an association between BDR and genotype at single nucleotide polymorphisms (SNPs). To increase power and distinguish between shared vs. population-specific associations with BDR in children with asthma, we performed a meta-analysis across 949 African Americans and 1,830 Latinos (Total=2,779). Lastly, we performed genome-wide admixture mapping to identify regions whereby local African or European ancestry is associated with BDR in African Americans. Two additional populations of 416 Latinos and 1,325 African Americans were used to replicate significant associations.ResultsWe identified a population-specific association with an intergenic SNP on chromosome 9q21 that was significantly associated with BDR (rs73650726, p=7.69 × 10−9). A trans-ethnic meta-analysis across African Americans and Latinos identified three additional SNPs within the intron of PRKG1 that were significantly associated with BDR (rs7903366, rs7070958, and rs7081864, p≤5 × 10−8).ConclusionsOur findings indicate that both population specific and shared genetic variation contributes to differences in BDR in minority children with asthma, and that the genetic underpinnings of BDR may differ between racial/ethnic groups.Key messagesA GWAS for BDR in African American children with asthma identified an intergenic population specific variant at 9q21 to be associated with increased bronchodilator drug response (BDR).A meta-analysis of GWAS across African Americans and Latinos identified shared genetic variants at 10q21 in the intron of PRKG1 to be associated with differences in BDR.Further genetic studies need to be performed in diverse populations to identify the full set of genetic variants that contribute to BDR.

Download Full-text

Genetic Variants Modifying the Triglycerides-Lowering Effect of Fish Oil Supplementation: A Genome-Wide Interaction Study

Current Developments in Nutrition ◽

10.1093/cdn/nzab050_006 ◽

2021 ◽

Vol 5 (Supplement_2) ◽

pp. 939-939

Author(s):

Michael Francis ◽

Changwei Li ◽

Yitang Sun ◽

Jingqi Zhou ◽

Xiang Li ◽

...

Keyword(s):

Fish Oil ◽

Gene Cluster ◽

Genetic Variants ◽

Meta Analysis ◽

Density Lipoprotein ◽

Lipoprotein Cholesterol ◽

Interaction Study ◽

Genome Wide ◽

A Genome ◽

Fish Oil Supplementation

Abstract Objectives To identify genetic variants that modify the effect of fish oil supplementation on blood lipids, including low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), total cholesterol, and triglycerides. Methods We performed a genome-wide interaction study in 73,962 participants of European ancestry from the UK Biobank. Candidate associations were evaluated in a replication study with 7,284 participants from the Atherosclerosis Risk in Communities (ARIC) Study. Meta-analysis was further performed across the two cohorts. Results Four novel interaction loci were identified at genome-wide significance in meta-analysis. The lead variant in the GJB6-GJB2-GJA3 gene cluster, rs112803755 (A > G; minor allele frequency = 0.041), shows an interaction effect but not the main effect, suggesting that it would not have been discovered in a typical association study. Fish oil supplementation is associated with a decreased blood level of triglycerides in individuals carrying the minor allele, but with an increased level in homozygotes of the major allele. This locus is significantly associated with higher GJB2 expression of connexin 26 in adipose tissue, while connexin activity is known to change upon exposure to omega-3 fatty acids. Significant interaction effects were also found in three other loci in the genes SLC12A3 (HDL-C), ABCA6 (LDL-C), and MLXIPL (LDL-C), but highly significant main effects are also present. Conclusions Our study identifies novel interaction effects for four genetic loci and highlights genetic variants in the GJB6-GJB2-GJA3 gene cluster, which modify the effects of fish oil supplementation on lowering blood triglycerides. These findings highlight the need and possibility for personalized nutrition. Funding Sources The University of Georgia Research Foundation

Download Full-text

A Genome-Wide Association Study and Polygenic Risk Score Analysis of Posttraumatic Stress Disorder and Metabolic Syndrome in a South African Population

Frontiers in Neuroscience ◽

10.3389/fnins.2021.677800 ◽

2021 ◽

Vol 15 ◽

Author(s):

Patricia C. Swart ◽

Leigh L. van den Heuvel ◽

Cathryn M. Lewis ◽

Soraya Seedat ◽

Sian M. J. Hemmings

Keyword(s):

Metabolic Syndrome ◽

South African ◽

Genetic Variants ◽

Genome Wide Association Study ◽

Stress Disorder ◽

Meta Analysis ◽

Genome Wide Association ◽

Polygenic Risk ◽

Genome Wide ◽

A Genome

Posttraumatic stress disorder (PTSD) is a trauma-related disorder that frequently co-occurs with metabolic syndrome (MetS). MetS is characterized by obesity, dyslipidemia, and insulin resistance. To provide insight into these co-morbidities, we performed a genome-wide association study (GWAS) meta-analysis to identify genetic variants associated with PTSD, and determined if PTSD polygenic risk scores (PRS) could predict PTSD and MetS in a South African mixed-ancestry sample. The GWAS meta-analysis of PTSD participants (n = 260) and controls (n = 343) revealed no SNPs of genome-wide significance. However, several independent loci, as well as five SNPs in the PARK2 gene, were suggestively associated with PTSD (p < 5 × 10–6). PTSD-PRS was associated with PTSD diagnosis (Nagelkerke’s pseudo R2 = 0.0131, p = 0.00786), PTSD symptom severity [as measured by CAPS-5 total score (R2 = 0.00856, p = 0.0367) and PCL-5 score (R2 = 0.00737, p = 0.0353)], and MetS (Nagelkerke’s pseudo R2 = 0.00969, p = 0.0217). These findings suggest an association between PTSD and PARK2, corresponding with results from the largest PTSD-GWAS conducted to date. PRS analysis suggests that genetic variants associated with PTSD are also involved in the development of MetS. Overall, the results contribute to a broader goal of increasing diversity in psychiatric genetics.

Download Full-text