Definitive Zygosity Scores in the Peas in the Pod Questionnaire is a Sensitive and Accurate Assessment of the Zygosity of Adult Twins.

Twin researchers face the challenge of accurately determining the zygosity of twins for research. As part of the annual questionnaire between 1999 and 2006, 8,307 twins from the TwinsUK registry were asked to complete five questions (independently from their co-twin) to ascertain their self-perceived zygosity during childhood on up to five separate occasions. This questionnaire is known as the 'peas in the pod' questionnaire (PPQ), but there is little evidence of its validation. Answers were scored and classified as monozygotic (MZ), dizygotic (DZ), or unknown zygosity (UZ) and were compared with 4,484 twins with genotyping data who had not been selected for zygosity. Of these, 3,859 individuals (46.5% of those who had a zygosity from PPQ) had zygosity classified by both the PPQ and genotyping. Of the 708 individual twins whose answers meant that they were consistently classed as MZ in the PPQ, 683 (96.5%) were MZ within the genotype data. Of the 945 individual twins consistently classed as DZ within questionnaire, 936 (99.0%) were DZ in the genotype data. Where both twins scored MZ consistently across multiple questionnaires, 99.6% were MZ on genotyping, 99.7% were DZ on genotyping if both twins consistently scored DZ. However, for the initial questionnaire, 88.6% of those scoring as MZ were genotypically MZ and 98.7% DZ. For twin pairs where both scored UZ, 94.7% were DZ. Using the PPQ on a single occasion provided a definitive classification of whether the twin was MZ or DZ with an overall accuracy of 86.9%, increasing to 97.9% when there was a consistent classification of zygosity across multiple questionnaires. This study has shown that the PPQ questionnaire is an excellent proxy indicator of zygosity in the absence of genotyping information.

Temporal-to-Nasal Macular Ganglion Cell and Inner Plexiform Layer Ratios in a Large Adult Twin Cohort: Correlations With Age and Heritability.

Purpose: Temporal-to-nasal macular ganglion cell layer thickness ratios are reduced in albinism. We explored similar ratios in a large twin cohort to investigate ranges in healthy adults, correlations with age, and heritability. Methods: More than 1000 twin pairs from TwinsUK underwent macular optical coherence tomography (OCT) scans. Automated segmentation yielded thicknesses for the combined ganglion cell and inner plexiform layer (GCIPL) in Early Treatment of Diabetic Retinopathy Study subfields. Participants with diseases likely to affect these layers or segmentation accuracy were excluded. Inner and outer ratios were defined as the ratio of temporal-to-nasal GCIPL thickness for inner and outer subfields respectively. Corresponding ratios were obtained from a smaller cohort undergoing OCTs with a different device (three-dimensional (3D)-OCT, Topcon, Japan). Results: Scans from 2300 twins (1150 pairs) were included (mean [SD] age, 53.9 (16.5) years). Mean (SD) inner and outer ratios were 0.89 (0.09) and 0.84 (0.11), correlating negatively with age (coefficients, -0.17 and -0.21, respectively). In males (150 pairs) ratios were higher and did not correlate significantly with age. Intrapair correlation coefficients were higher in monozygotic than dizygotic pairs; age-adjusted heritability estimates were 0.20 and 0.23 for inner and outer ratios, respectively. For the second cohort (n = 166), mean (SD) ratios were 0.93 (0.08) and 0.91 (0.09), significantly greater than for the larger cohort. Conclusions: Our study gives reference values for temporal-to-nasal macular GCIPL subfield ratios. Weak negative correlations with age emerged. Genetic factors may contribute to ∼20% to 23% of the variance in healthy individuals. The ratios differ according to the OCT platform used.

Glaucoma Patients Have a Lower Abundance of Butyrate-Producing Taxa in the Gut.

Purpose: Glaucoma is an eye disease that is the most common cause of irreversible blindness worldwide. It has been suggested that gut microbiota can produce reactive oxygen species and pro-inflammatory cytokines that may travel from the gastric mucosa to distal sites, for example, the optic nerve head or trabecular meshwork. There is evidence for a gut-eye axis, as microbial dysbiosis has been associated with retinal diseases. We investigated the microbial composition in patients with glaucoma and healthy controls. Moreover, we analyzed the association of the gut microbiome with intraocular pressure (IOP; risk factor of glaucoma) and vertical cup-to-disc ratio (VCDR; quantifying glaucoma severity). Methods: The discovery analyses included participants of the Rotterdam Study and the Erasmus Glaucoma Cohort. A total of 225 patients with glaucoma and 1247 age- and sex-matched participants without glaucoma were included in our analyses. Stool samples were used to generate 16S rRNA gene profiles. We assessed associations with 233 genera and species. We used data from the TwinsUK and the Study of Health in Pomerania (SHIP) to replicate our findings. Results: Several butyrate-producing taxa (e.g. Butyrivibrio, Caproiciproducens, Clostridium sensu stricto 1, Coprococcus 1, Ruminococcaceae UCG 007, and Shuttleworthia) were less abundant in people with glaucoma compared to healthy controls. The same taxa were also associated with lower IOP and smaller VCDR. The replication analyses confirmed the findings from the discovery analyses. Conclusions: Large human studies exploring the link between the gut microbiome and glaucoma are lacking. Our results suggest that microbial dysbiosis plays a role in the pathophysiology of glaucoma.

Prevalence, Concordance, and Heritability of Vitreomacular Interface Abnormalities in a Twin Study.

Purpose: The relative importance of genetic factors in common vitreomacular interface (VMI) abnormalities is unknown. The aim of this classical twin study is to determine the prevalence case wise concordance between monozygotic and dizygotic twin pairs, and heritability of common VMI abnormalities, including epiretinal membrane (ERM), posterior vitreous detachment (PVD), vitreomacular adhesion (VMA), vitreomacular traction (VMT), lamellar macular holes (LMHs), and full-thickness macular holes (FTMHs). Methods: This is a single-center, cross-sectional classical twin study of 3406 TwinsUK participants over the age of 40 years who underwent spectral domain macular optical coherence tomography (SD-OCT) scans which were graded for signs of VMI abnormalities. Case wise concordance was calculated and the heritability of each VMI abnormality was estimated using OpenMx structural equation modeling. Results: In this population (mean age = 62.0 years [SD = 10.4 years], range = 40-89 years) the overall prevalence of ERM was 15.6% (95% confidence interval [CI] = 14.4-16.9) and increased with age, posterior vitreous detachment affected 21.3% (20.0-22.7), and VMA was diagnosed in 11.8% (10.8-13.0). Monozygotic twins were more concordant for all traits than dizygotic twins, and age, spherical equivalent refraction (SER), and lens status-adjusted heritability was estimated at 38.9% (95% CI = 33.6-52.8) for ERM, 53.2% (95% CI = 41.8-63.2) for PVD, and 48.1% (95% CI = 33.6-58) for VMA. Conclusions: Common VMI abnormalities are heritable and therefore have an underlying genetic component. Given the sight-threatening potential of VMI abnormalities, further genetic studies, such as genomewide association studies, would be useful to identify genes and pathways implicated in their pathogenesis.