Large scale international replication and meta-analysis study confirms association of the 15q14 locus with myopia. The CREAM consortium.

Myopia is a complex genetic disorder and a common cause of visual impairment among working age adults. Genome-wide association studies have identified susceptibility loci on chromosomes 15q14 and 15q25 in Caucasian populations of European ancestry. Here, we present a confirmation and meta-analysis study in which we assessed whether these two loci are also associated with myopia in other populations.

Common genetic determinants of intraocular pressure and primary open-angle glaucoma.

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.

The ERCC6 gene and age-related macular degeneration.

Background: Age-related macular degeneration (AMD) is the leading cause of irreversible visual loss in the developed countries and is caused by both environmental and genetic factors. A recent study (Tuo et al., PNAS) reported an association between AMD and a single nucleotide polymorphism (SNP) (rs3793784) in the ERCC6 (NM_000124) gene.

A genome-wide association study identifies a susceptibility locus for refractive errors and myopia at 15q14.

Refractive errors are the most common ocular disorders worldwide and may lead to blindness. Although this trait is highly heritable, identification of susceptibility genes has been challenging. We conducted a genome-wide association study for refractive error in 5,328 individuals from a Dutch population-based study with replication in four independent cohorts (combined 10,280 individuals in the replication stage).

Association of cognitive functioning with retinal nerve fiber layer thickness.

Purpose: The brain areas that are responsible for cognitive functioning have the same embryonic origin as the retina. The association between cognitive functioning and retinal nerve fiber layer (RNFL) thickness was assessed in a large, population-based sample.

Methods: Neuropsychological and ophthalmic examinations were performed in 1485 healthy individuals (mean age, 46 years; range, 18-85) from the Erasmus Rucphen Family (ERF) study, a study in a genetic isolate from the Netherlands.

Complement component C3 and risk of age-related macular degeneration.

Objective: To explore the association between polymorphisms in the complement component 3 (C3) gene and age-related macular degeneration (AMD), and to investigate the modifying effect of complement factor H (CFH) Y402H, LOC387715 A69S and smoking.

Design: Pooled data from the prospective, population-based Rotterdam Study (enrolment between 1990 and 1993, and 3 follow-up examinations between September 1, 1993, and December 31, 2004) and an independent case-control study from the Netherlands.

Participants: The Rotterdam Study comprised a total of 6418 persons aged >or=55 years who had gradable fundus photographs.

Three genome-wide association studies and a linkage analysis identify HERC2 as a human iris color gene.

Human iris color was one of the first traits for which Mendelian segregation was established. To date, the genetics of iris color is still not fully understood and is of interest, particularly in view of forensic applications. In three independent genome-wide association (GWA) studies of a total of 1406 persons and a genome-wide linkage study of 1292 relatives, all from the Netherlands, we found that the 15q13.

Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration.

Purpose: To determine whether variants in the candidate genes TLR4, CCL2, and CCR2 are associated with age-related macular degeneration (AMD).

Methods: This study was performed in two independent Caucasian populations that included 357 cases and 173 controls from the Netherlands and 368 cases and 368 controls from the United States. Exon 4 of the TLR4 gene and the promoter, all exons, and flanking intronic regions of the CCL2 and CCR2 genes were analyzed in the Dutch study and common variants were validated in the U.

Usefulness of combining complement factor H and C-reactive protein genetic profiles for predicting myocardial infarction (from the Rotterdam Study).

Complement factor H (CFH) is an important regulator of the complement cascade. Binding of C-reactive protein (CRP) to CFH augments the ability of CFH to downregulate the effect of complement in atherosclerotic lesions. The CFH Tyr402His polymorphism has been suggested to influence the ability of CFH to bind CRP.

Genetic contributions to glaucoma: heritability of intraocular pressure, retinal nerve fiber layer thickness, and optic disc morphology.

Purpose: The genetic etiology of primary open-angle glaucoma (POAG) is still largely unknown, because of its complexity and disparities in its classification. This study was undertaken to determine the genetic contribution to various early, continuous markers of POAG by assessing the heritability of intraocular pressure (IOP), retinal nerve fiber layer (RNFL) thickness, and neuroretinal rim and optic disc parameters in a genetically isolated population.

Methods: A total of 2620 subjects (mean age, 48 years; range 18-86) from extended pedigrees living in a small town in The Netherlands underwent an extensive ophthalmic examination.

Complement factor h polymorphism, inflammatory mediators, and retinal vessel diameters: the rotterdam study.

Purpose: Retinal venular dilatation is associated with systemic inflammation. The hypothesis for the current study was that larger retinal venular diameters are related to the His allele of the Tyr402His polymorphism in the complement factor H (CFH) gene, a major inhibitor of the complement pathway. Possible effect modification by smoking and inflammatory markers was examined.

Complement factor H polymorphism, complement activators, and risk of age-related macular degeneration.

Context: The evidence that inflammation is an important pathway in age-related macular degeneration (AMD) is growing. Recent case-control studies demonstrated an association between the complement factor H (CFH) gene, a regulator of complement, and AMD.

Objectives: To assess the associations between the CFH gene and AMD in the general population and to investigate the modifying effect of smoking, serum inflammatory markers, and genetic variation of C-reactive protein (CRP).

A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: the Rotterdam Study.

Objectives: This study was designed to investigate the association between a common polymorphism (Tyr402His, rs1061170) in the complement factor H (CFH) gene and risk of coronary heart disease.

Background: The evidence that inflammation is an important mechanism in atherogenesis is growing. C-reactive protein (CRP), complement factors, and complement regulatory factors have all been linked to coronary heart disease.