Heritability of intraocular pressure: a classical twin study

Carbonaro, Francis; Andrew, Toby; Mackey, David A.; Spector, Tim D.; Hammond, Chris

doi:10.1136/bjo.2007.133272

Cited by 32 publications

(25 citation statements)

References 59 publications

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“…Several European population studies have reported IOP data [5–9]. However, individual studies suffer from limited sample size and results may only apply to the geographical region examined.…”

Section: Introductionmentioning

confidence: 99%

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

et al. 2016

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Raised intraocular pressure (IOP) is the most important risk factor for developing glaucoma, the second commonest cause of blindness globally. Understanding associations with IOP and variations in IOP between countries may teach us about mechanisms underlying glaucoma. We examined cross-sectional associations with IOP in 43,500 European adults from 12 cohort studies belonging to the European Eye Epidemiology (E3) consortium. Each study conducted multivariable linear regression with IOP as the outcome variable and results were pooled using random effects meta-analysis. The association of standardized study IOP with latitude was tested using meta-regression. Higher IOP was observed in men (0.18 mmHg; 95 % CI 0.06, 0.31; P = 0.004) and with higher body mass index (0.21 mmHg per 5 kg/m2; 95 % CI 0.14, 0.28; P < 0.001), shorter height (−0.17 mmHg per 10 cm; 95 % CI –0.25, −0.08; P < 0.001), higher systolic blood pressure (0.17 mmHg per 10 mmHg; 95 % CI 0.12, 0.22; P < 0.001) and more myopic refraction (0.06 mmHg per Dioptre; 95 % CI 0.03, 0.09; P < 0.001). An inverted U-shaped trend was observed between age and IOP, with IOP increasing up to the age of 60 and decreasing in participants older than 70 years. We found no significant association between standardized IOP and study location latitude (P = 0.76). Novel findings of our study include the association of lower IOP in taller people and an inverted-U shaped association of IOP with age. We found no evidence of significant variation in IOP across Europe. Despite the limited range of latitude amongst included studies, this finding is in favour of collaborative pooling of data from studies examining environmental and genetic determinants of IOP in Europeans.Electronic supplementary materialThe online version of this article (doi:10.1007/s10654-016-0191-1) contains supplementary material, which is available to authorized users.

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Section: Introductionmentioning

confidence: 99%

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

et al. 2016

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“…An elevated IOP (>21 mmHg) influences both the onset and the progression of glaucoma [14]. Genetic effects have been shown to account for a significant proportion of the variance in IOP, with heritability estimates ranging from 0.29 to 0.67 [15]–[19]. Five genome-wide linkage studies of IOP have been performed [20]–[24].…”

Section: Introductionmentioning

confidence: 99%

Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma

et al. 2012

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Intraocular pressure (IOP) is a highly heritable risk factor for primary open-angle glaucoma and is the only target for current glaucoma therapy. The genetic factors which determine IOP are largely unknown. We performed a genome-wide association study for IOP in 11,972 participants from 4 independent population-based studies in The Netherlands. We replicated our findings in 7,482 participants from 4 additional cohorts from the UK, Australia, Canada, and the Wellcome Trust Case-Control Consortium 2/Blue Mountains Eye Study. IOP was significantly associated with rs11656696, located in GAS7 at 17p13.1 (p = 1.4×10−8), and with rs7555523, located in TMCO1 at 1q24.1 (p = 1.6×10−8). In a meta-analysis of 4 case-control studies (total N = 1,432 glaucoma cases), both variants also showed evidence for association with glaucoma (p = 2.4×10−2 for rs11656696 and p = 9.1×10−4 for rs7555523). GAS7 and TMCO1 are highly expressed in the ciliary body and trabecular meshwork as well as in the lamina cribrosa, optic nerve, and retina. Both genes functionally interact with known glaucoma disease genes. These data suggest that we have identified two clinically relevant genes involved in IOP regulation.

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“…IOP is a heritable trait, with heritability estimates ranging from 0.35 to 0.74 in different studies (5–7). Investigating genetic variation influencing IOP might help better understand IOP regulation and its role in glaucoma pathophysiology.…”

Section: Introductionmentioning

confidence: 99%

A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort

Nag

Venturini²,

Small

et al. 2014

Human Molecular Genetics

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Glaucoma is a major cause of blindness in the world. To date, common genetic variants associated with glaucoma only explain a small proportion of its heritability. We performed a genome-wide association study of intra-ocular pressure (IOP), an underlying endophenotype for glaucoma. The discovery phase of the study was carried out in the TwinsUK cohort (N = 2774) analyzing association between IOP and single nucleotide polymorphisms (SNPs) imputed to HapMap2. The results were validated in 12 independent replication cohorts of European ancestry (combined N = 22 789) that were a part of the International Glaucoma Genetics Consortium. Expression quantitative trait locus (eQTL) analyses of the significantly associated SNPs were performed using data from the Multiple Tissue Human Expression Resource (MuTHER) Study. In the TwinsUK cohort, IOP was significantly associated with a number of SNPs at 9q33.3 (P = 3.48 × 10−8 for rs2286885, the most significantly associated SNP at this locus), within the genomic sequence of the FAM125B gene. Independent replication in a composite panel of 12 cohorts revealed consistent direction of effect and significant association (P = 0.003, for fixed-effect meta-analysis). Suggestive evidence for an eQTL effect of rs2286885 was observed for one of the probes targeting the coding region of the FAM125B gene. This gene codes for a component of a membrane complex involved in vesicular trafficking process, a function similar to that of the Caveolin genes (CAV1 and CAV2) which have previously been associated with primary open-angle glaucoma. This study suggests a novel association between SNPs in FAM125B and IOP in the TwinsUK cohort, though further studies to elucidate the functional role of this gene in glaucoma are necessary.

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Heritability of intraocular pressure: a classical twin study

Cited by 32 publications

References 59 publications

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

Associations with intraocular pressure across Europe: The European Eye Epidemiology (E3) Consortium

Common Genetic Determinants of Intraocular Pressure and Primary Open-Angle Glaucoma

A genome-wide association study of intra-ocular pressure suggests a novel association in the gene FAM125B in the TwinsUK cohort

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