Genetic pre-screening for glaucoma in population-based epidemiology: protocol for a double-blind prospective screening study within Lifelines (EyeLife)

Neustaeter, Anna; Nolte, Ilja M.; Snieder, Harold; Jansonius, Nomdo M.

doi:10.1186/s12886-020-01771-9

Cited by 12 publications

(6 citation statements)

References 49 publications

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“…Following quality control, both genotyping datasets were then imputed into the Sanger imputation server using the Haplotype Reference Consortium panel r1.1 [ 24 ]. Details of genotyping, quality control, and imputation in Lifelines have been published elsewhere [ 25 ].…”

Section: Methodsmentioning

confidence: 99%

Do Poor Diet and Lifestyle Behaviors Modify the Genetic Susceptibility to Impulsivity in the General Population?

et al. 2023

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The present study investigated whether an unhealthy diet and other lifestyle behaviors may modify the genetic susceptibility to impulsivity. A total of 33,047 participants (mean age = 42.1 years, 59.8% females) from the Dutch Lifelines cohort were included. Each diet index and other lifestyle behaviors were tested for their interactions on the effect on the attention-deficit/hyperactivity disorder (ADHD) polygenic risk score (PRS) on impulsivity using a linear regression model with adjustment for covariates. The ADHD PRS was significantly associated with impulsivity (B = 0.03 (95% CI: 0.02, 0.04); p = 2.61 × 10−9). A poorer diet, a higher intake of energy, and a higher intake of fat were all associated with higher impulsivity, and a high intake of energy amplified the effect of ADHD PRS on impulsivity (e.g., for the interaction term of ADHD PRS and highest tertile on intake of energy, B = 0.038 (95% CI: 0.014, 0.062); p = 0.002. The other lifestyle factors, namely short and long sleep duration, current and past smoking, higher alcohol intake, and more time spent on moderate-to-vigorous physical activity were associated with higher impulsivity, but no interaction effect was observed. In conclusion, we found that a high intake of energy exacerbated the genetic susceptibility to impulsivity. Our study helps to improve our understanding of the role of diet and genetic factors on impulsivity.

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Section: Methodsmentioning

confidence: 99%

Do Poor Diet and Lifestyle Behaviors Modify the Genetic Susceptibility to Impulsivity in the General Population?

et al. 2023

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“…After quality control, both genotyping datasets were then imputed at the Sanger imputation server using the Haplotype Reference Consortium panel r1.1 36 . Details of genotyping, quality control, and imputation in Lifelines have been published elsewhere 37 . Two PRSs of ASD were calculated in the Lifelines samples based on the summary statistics of ASD GWAS and ASD MTAG results, respectively.…”

Section: Prs Analysesmentioning

confidence: 99%

Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, pain, and fatigue

Li,

Xie,

Snieder

et al. 2023

Preprint

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Autism spectrum disorder (ASD) often co-occurs with functional somatic syndromes (FSS), such as irritable bowel syndrome (IBS), pain, and fatigue. However, the underlying genetic mechanisms and causality have not been well studied. Using large-scale genome-wide association study (GWAS) data, we investigated the shared genetic architecture and causality between ASD and FSS. Specifically, we first estimated genetic correlations and then conducted a multi-trait analysis of GWAS (MTAG) to detect potential novel genetic variants for single traits. Afterwards, polygenic risk scores (PRS) of ASD were derived from GWAS and MTAG to examine the associations with phenotypes in the large Dutch Lifelines cohort. Finally, we performed Mendelian randomization (MR) to evaluate the causality. We observed positive genetic correlations between ASD and FSS (IBS: rg = 0.27, adjusted p = 2.04×10− 7; pain: rg = 0.13, adjusted p = 1.10×10− 3; fatigue: rg = 0.33, adjusted p = 5.21×10− 9). Leveraging these genetic correlations, we identified 4 novel genome-wide significant independent loci for ASD by conducting MTAG, including NEDD4L, MFHAS1, RP11-10A14.4, and C8orf74. PRS of ASD derived from both GWAS and MTAG were associated with ASD and FSS symptoms in Lifelines, and MTAG-derived PRS showed a bigger effect size, larger explained variance, and smaller p-values. We did not observe significant causality using MR. Our study provided new evidence of shared genetic architecture between ASD and FSS, specifically with IBS, pain, and fatigue. The findings confirm the genetic associations between ASD and FSS, and advance our understanding of the mechanisms underlying co-occurrence.

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“…GRS have not yet been established as a clinical screening tool for POAG. Neustaeter and colleagues are testing feasibility of POAG GRS for clinical screening using a prospective approach [38], but the variants included in the GRS were identified from POAG GWAS in European-descent individuals. In European-descent samples, a higher burden of genetic risk captured by PRS is associated with POAG age at diagnosis and disease-relevant clinical parameters [15,16].…”

Section: Clinical Applicability Of Genetic Data In Poag Risk Stratifi...mentioning

confidence: 99%

Diversity in Polygenic Risk of Primary Open-Angle Glaucoma

Bailey

Funk

Cruz

et al. 2022

Genes

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Glaucoma is the leading cause of irreversible blindness worldwide. Primary open-angle glaucoma (POAG), the most common glaucoma subtype, is more prevalent and severe in individuals of African ancestry. Unfortunately, this ancestral group has been historically under-represented among genetic studies of POAG. Moreover, both genetic and polygenic risk scores (GRS, PRS) that are typically based on genetic data from European-descent populations are not transferable to individuals without a majority of European ancestry. Given the aspirations of leveraging genetic information for precision medicine, GRS and PRS demonstrate clinical potential but fall short, in part due to the lack of diversity in these studies. Prioritizing diversity in the discovery of risk variants will improve the performance and utility of GRS and PRS-derived risk estimation for disease stratification, which could bring about earlier POAG intervention and treatment for a disease that often goes undetected until significant damage has occurred.

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Genetic pre-screening for glaucoma in population-based epidemiology: protocol for a double-blind prospective screening study within Lifelines (EyeLife)

Cited by 12 publications

References 49 publications

Do Poor Diet and Lifestyle Behaviors Modify the Genetic Susceptibility to Impulsivity in the General Population?

Do Poor Diet and Lifestyle Behaviors Modify the Genetic Susceptibility to Impulsivity in the General Population?

Shared genetic architecture and causality between autism spectrum disorder and irritable bowel syndrome, pain, and fatigue

Diversity in Polygenic Risk of Primary Open-Angle Glaucoma

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