Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function

Gibraltar Neanderthals and results of recent excavations in Gorham's, Vanguard and Ibex Caves

While the sites of Forbes' Quarry and Devil's Tower are, respectively, unpromising and probably too dangerous for further excavation, there are several other sites on the Rock preserving evidence of Neanderthal activities. One, Ibex Cave, lies high up on the eastern face of the Rock, while four others lie to the southeast, close to the sea near 'Governor's Beach'. The present beach mainly consists of fine limestone blast debris from military tunnelling operations, but there are also cemented remnants of more ancient beaches which presumably accumulated during Oxygen Isotope Stage 5. The caves are named (from the south) Bennett's, Gorham's, Vanguard and Boat Hoist. Three of these caves (Ibex, Gorham's and Vanguard) have been excavated since 1994 as part of the Gibraltar Caves Project; some of the initial results of this work are presented below. Further details will appear in the proceedings of the Gibraltar conference held in August to celebrate the 150th anniversary of the finding of the Forbes' Quarry skull (Stringer et al. in preparation). The excavations at Gorham's and Vanguard Caves are already beginning to yield significant results relating to the palaeontological, archaeological and palaeoenvironmental aspects of the Neanderthals and their modern human successors. The integration of new AMS and other dating results with sediments analysis should help us compare the sequences in both caves and to provide frameworks for situating human behaviour. For example, it would be interesting to know whether changes in sea level and resulting reconfiguration of the coastal plain were major factors responsbile in the Neanderthal exploitation of highly local raw materials for tool-making and the frequency of gathering of marine/estuarine foods. Using this information and comparing the archaeological evidence from the Middle and Upper Palaeolithic levels at the sites will help to place the Gibraltar finds in their European and Mediterranean contexts

Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images (vol 17, e1009497, 2021)

[This corrects the article DOI: 10.1371/journal.pgen.1009497.]

Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort: The UK Biobank.

PURPOSE: To describe and compare associations with macular retinal nerve fiber layer (mRNFL), ganglion cell complex (GCC), and ganglion cell-inner plexiform layer (GCIPL) thicknesses in a large cohort. DESIGN: Cross-sectional study. PARTICIPANTS: We included 42 044 participants in the UK Biobank. The mean age was 56 years. METHODS: Spectral-domain OCT macular images were segmented and analyzed. Corneal-compensated intraocular pressure (IOPcc) was measured with the Ocular Response Analyzer (Reichert, Corp., Buffalo, NY). Multivariable linear regression was used to examine associations with mean mRNFL, GCC, and GCIPL thicknesses. Factors examined were age, sex, ethnicity, height, body mass index (BMI), smoking status, alcohol intake, Townsend deprivation index, education level, diabetes status, spherical equivalent, and IOPcc. MAIN OUTCOME MEASURES: Thicknesses of mRNFL, GCC, and GCIPL. RESULTS: We identified several novel independent associations with thinner inner retinal thickness. Thinner inner retina was associated with alcohol intake (most significant for GCIPL: -0.46 μm for daily or almost daily intake compared with special occasion only or never [95% confidence interval (CI), 0.61-0.30]; P = 1.1×10-8), greater social deprivation (most significant for GCIPL: -0.28 μm for most deprived quartile compared with least deprived quartile [95% CI, -0.42 to -0.14]; P = 6.6×10-5), lower educational attainment (most significant for mRNFL: -0.36 μm for less than O level compared with degree level [95% CI, -0.45 to 0.26]; P = 2.3×10-14), and nonwhite ethnicity (most significant for mRNFL comparing blacks with whites: -1.65 μm [95% CI, -1.86 to -1.43]; P = 2.4×10-50). Corneal-compensated intraocular pressure was associated most significantly with GCIPL (-0.04 μm/mmHg [95% CI, -0.05 to -0.03]; P = 4.0×10-10) and was not associated significantly with mRNFL (0.00 μm/mmHg [95% CI, -0.01 to 0.01]; P = 0.77). The variables examined explained a greater proportion of the variance of GCIPL (11%) than GCC (6%) or mRNFL (7%). CONCLUSIONS: The novel associations we identified may be important to consider when using inner retinal parameters as a diagnostic tool. Associations generally were strongest with GCIPL, particularly for IOP. This suggests that GCIPL may be the superior inner retinal biomarker for macular pathophysiologic processes and especially for glaucoma

Genetic variation affects morphological retinal phenotypes extracted from UK Biobank optical coherence tomography images.

Optical Coherence Tomography (OCT) enables non-invasive imaging of the retina and is used to diagnose and manage ophthalmic diseases including glaucoma. We present the first large-scale genome-wide association study of inner retinal morphology using phenotypes derived from OCT images of 31,434 UK Biobank participants. We identify 46 loci associated with thickness of the retinal nerve fibre layer or ganglion cell inner plexiform layer. Only one of these loci has been associated with glaucoma, and despite its clear role as a biomarker for the disease, Mendelian randomisation does not support inner retinal thickness being on the same genetic causal pathway as glaucoma. We extracted overall retinal thickness at the fovea, representative of foveal hypoplasia, with which three of the 46 SNPs were associated. We additionally associate these three loci with visual acuity. In contrast to the Mendelian causes of severe foveal hypoplasia, our results suggest a spectrum of foveal hypoplasia, in part genetically determined, with consequences on visual function

The British Late Middle Palaeolithic: An Interpretative Synthesis of Neanderthal Occupation at the Northwestern Edge of the Pleistocene World

The British Middle Palaeolithic is divided into two discrete periods of occupation: the Early Middle Palaeolithic (MIS 9–7, ~330–180 ka BP) and the Late Middle Palaeolithic (MIS 3, ~59–36 ka BP), separated by a long hiatus. Owing to the relative poverty of the record and historical difficulties in dating and correlating archaeological sites, the British Late Middle Palaeolithic has, until recently, received scant attention, and has largely been regarded as the poor man of Europe, especially by British archaeologists. Indeed, there has been more discussion of the absence of humans from Britain than of what they did when they were present. We aim here to redress that situation. Following from recent considerations of the Early Middle Palaeolithic (White et al. in J. Quat. Sci. 21:525–542, 2006; Scott, Becoming Neanderthal, Oxbow, Oxford, 2010), we offer an interpretative synthesis of the British Late Middle Palaeolithic, situating ‘British’ Neanderthals in their chronological, environmental and landscape contexts. We discuss the character of the British record, and offer an account of Neanderthal behaviour, settlement systems and technological practices at the northwestern edge of their known Upper Pleistocene range. We also examine the relationship of the enigmatic Early Upper Palaeolithic leafpoint assemblages to Neanderthals