Cohort profile: design and methods in the eye and vision consortium of UK Biobank

PURPOSE: To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. PARTICIPANTS: UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. FINDINGS TO DATE: A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. FUTURE PLANS: UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life

Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development

A genetic contribution to refractive error has been confirmed by the discovery of more than 150 associated variants in genome-wide association studies (GWAS). Environmental factors such as education and time outdoors also demonstrate strong associations. Currently however, the extent of gene-environment or gene-gene interactions in myopia is unknown. We tested the hypothesis that refractive error-associated variants exhibit effect size heterogeneity, a hallmark feature of genetic interactions. Of 146 variants tested, evidence of non-uniform, non-linear effects were observed for 66 (45%) at Bonferroni-corrected significance (P < 1.1 × 10−4) and 128 (88%) at nominal significance (P < 0.05). LAMA2 variant rs12193446, for example, had an effect size varying from −0.20 diopters (95% CI −0.18 to −0.23) to −0.89 diopters (95% CI −0.71 to −1.07) in different individuals. SNP effects were strongest at the phenotype extremes and weaker in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in myopia are pervasive

Current debates on immunology of preeclampsia. Report of the sixth international workshop of Reunion Island (Indian Ocean, December 2008)

Les troubles hypertensifs de la grossesse (THG) représentent globalement 10 % des naissances humaines, et leur complication majeure, la prééclampsie, 3 à 5 %. L’étiologie de ces THG reste toujours controversée ; cependant des avancées majeures ont eu lieu ces dernieres 25 années. Le « sixième colloque international d’immunologie de la reproduction, de l’immunotolérance et de l’immunologie de la prééclampsie » 2008 a fêté cette année son dixième anniversaire. Durant cette décennie, ces six colloques bisannuels ont largement contribué à nourrir le débat entre immunologistes, cliniciens, anthropologues et spécialistes des maladies cardiovasculaires. Le défaut de l’invasion trophoblastique profonde obligatoire chez les humains rencontrée dans la prééclampsie, le retard de croissance intra-utérin, et dans une certaine mesure dans la menace d’accouchement prématuré n’ont été compris qu’à la fin des années 1970. Dans le même temps, des études cliniques et épidémiologiques à la fin du xxe siècle ont permis de réaliser que la prééclampsie « maladie des primipares » pouvait en fait être une maladie de la première grossesse au niveau d’un couple. Parmi les avancées significatives, l’immunologie de la reproduction a fait des bonds de géant dans la dernière décennie. Ce papier relate les étapes majeures franchies dans la compréhension de cette pathologie et met en lumière l’intérêt de ces travaux immunologiques et des nouveaux concepts afférents. Il semble, en ce début de xxie siècle que nous soyons plus près que jamais de comprendre l’étiologie de cette énigme obstétricale. Dans ce domaine, l’immunologie de la reproduction sera sans doute un des interlocuteurs majeurs.Hypertensive disorders of pregnancy (HDP) represent globally 10% of human births and their major complication, preeclampsia, 3 to 5%. The etiology of these HDP remains still uncertain, however major advances have been made these last 25 years. The Sixth International Workshop on Reproductive Immunology, Immunological Tolerance and Immunology of Preeclampsia 2008 celebrated its 10th Anniversary in Reunion-island (French overseas Department in the Indian Ocean). Over this decade, these six workshops have contributed extensively to immunological, epidemiological, anthropological and even vascular debates. The defect of trophoblastic invasion encountered in preeclampsia, intra-uterine growth retardation and to some extend also preterm labour has been understood only at the end of the 1970's. On the other hand, clinical and epidemiological findings at the end of the 20th century permitted to apprehend that “preeclampsia disease of primiparae” may in fact well be the disease of first pregnancies at the level of human couples. Among the important advances, immunology of reproduction is certainly the topic where knowledge has literally exploded in the last decade. This paper relates some major steps in comprehension of this disease and focuses on the interest to follow these immunological works and their new concepts. It seems, at the beginning of the 21st century, that we are possibly closer than ever to understand the etiology of this obstetrical enigma. In this quest, the immunology of reproduction will certainly come out as one of the main players