Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study.
Ontology highlight
ABSTRACT:
SUBMITTER: Iyengar SK
PROVIDER: S-EPMC521942 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:ObjectiveTo examine the associations of cataract and cataract surgery with early and late age-related macular degeneration (AMD) over a 20-year interval.DesignLongitudinal population-based study of age-related eye diseases.ParticipantsBeaver Dam Eye Study participants.MethodsPersons aged 43 to 86 years participated in the baseline examination in 1988-1990. Participants were followed up at 5-year intervals after the baseline examination. Examinations consisted of ocular examination with lens and fundus photography, medical history, measurements of blood pressure, height, and weight. Values of risk variables were updated, and incidences of early and late AMD were calculated for each 5-year interval. Odds ratios were computed using discrete linear logistic regression modeling with generalized estimating equation methods to account for correlation between the eyes and multiple intervals.Main outcome measuresAge-related macular degeneration.ResultsAfter adjusting for age and sex, neither cataract nor cataract surgery was associated with increased odds for developing early AMD. Further adjusting for high-risk gene alleles (CFH and ARMS2) and other possible risk factors did not materially affect the odds ratio (OR). However, cataract surgery was associated with incidence of late AMD (OR 1.93; 95% confidence interval [CI], 1.28-2.90). This OR was not materially altered by further adjusting for high-risk alleles (CFH Y402H, ARMS2) or other risk factors. The OR for late AMD was higher for cataract surgery performed 5 or more years prior compared with less than 5 years prior.ConclusionsThese data strongly support the past findings of an association of cataract surgery with late AMD independent of other risk factors, including high-risk genetic status, and suggest the importance of considering these findings when counseling patients regarding cataract surgery. These findings should provide further impetus for the search for measures to prevent or delay the development of age-related cataract.
| S-EPMC3411928 | biostudies-literature
Project description:We tested the hypothesis that large areas of small hard drusen (diameter <63 μm) and intermediate drusen (diameter 63-124 μm) are associated with the incidence of age-related macular degeneration (AMD). Eyes of 3344 older adults with at least 2 consecutive visits spaced 5 years apart over a 20-year period were included. A 6-level severity scale including no drusen, 4 levels of increasing area (from minimal [<2596 μm(2)] to large [>9086 μm(2)]) of only small hard drusen, and intermediate drusen was used. The 5-year incidence of AMD was 3% in eyes at the start of the interval with no, minimal, small, and moderate areas of only small drusen and 5% and 25% for eyes with large area of only small drusen and intermediate drusen, respectively. Compared to eyes with a moderate area of small drusen, the odds ratio (OR) of developing AMD in eyes with a large area of only small drusen was 1.8 (P<.001). Compared to eyes with large area of only small drusen, eyes with intermediate drusen had an OR of 5.5 (P<0.001) of developing AMD. Our results are consistent with our hypothesis that large areas of only small drusen are associated with the incidence of AMD.
| S-EPMC4402933 | biostudies-literature
Project description:To determine if skin intrinsic fluorescence (SIF), a noninvasive measure of advanced glycation endproducts and oxidative stress in skin is associated with AMD.SIF was measured with the SCOUT DS skin fluorescence spectrometer in a cross-sectional cohort study of 969 persons aged 68 to 102 years from the 1181 who participated in the 25-year follow-up examination in the Beaver Dam Eye Study (BDES) in 2014 to 2016. The SCOUT DS skin fluorescence spectrometer uses five light-emitting diodes, centered at 375 nm to 456 nm. AMD was assessed by grading of digital color 45° stereoscopic fundus photographs of the macula using the Wisconsin Age-Related Maculopathy grading scheme. Analyses included logistic regression with generalized estimating equations to account for correlation between the eyes of a person.There were data for 1827 eyes for analyses. Early AMD was present in 22% and late AMD in 4% of the eyes. While adjusting for age, sex, smoking status, and history of cardiovascular disease, there were no significant associations of any SIF measure with any AMD or exudative AMD. SIF01 (odds ratio per 1 SD difference on the log scale, 95% confidence interval) (1.66, 1.00-2.74, P = 0.05) and SIF03 (1.81, 1.16-2.81, P = 0.008) were associated with geographic atrophy.There was a suggestive relationship of two SIF measures, SIF01 and SIF03, using different correction factors from the excitation centered at 375 nm, with the prevalence of geographic atrophy in the BDES. Longitudinal follow-up is indicated to assess a temporal relationship.
| S-EPMC5742994 | biostudies-literature
Project description:To examine the association of vasodilator and antihypertensive medication use with the incidence of age-related macular degeneration (AMD).Longitudinal population-based study.Persons 43 to 86 years of age living in Beaver Dam, Wisconsin, from 1988 through 1990.Examinations were performed every 5 years over a 20-year period. There were 9676 total person-visits over the course of the study. Status of AMD was determined from grading retinal photographs.Incidence of AMD.The 5-year incidence of early AMD over the 20-year period was 8.4%; for late AMD, it was 1.4%; for pure geographic atrophy (GA), it was 0.6%; for exudative AMD, it was 0.9%; and for progression of AMD, it was 24.9%. While adjusting for age, gender, and other factors, using a vasodilator (hazard ratio [HR], 1.72; 95% confidence interval [CI], 1.25-2.38), particularly oral nitroglycerin (HR, 1.81; 95% CI, 1.14-2.90), was associated with an increased risk of early AMD. Using an oral ?-blocker was associated with an increased hazard of incident exudative AMD (HR, 1.71; 95% CI, 1.04-2.82), but not pure GA (HR, 0.51; 95% CI, 0.20-1.29) or progression of AMD (HR, 0.92; 95% CI, 0.67-1.28) over the 20-year period.Use of vasodilators is associated with a 72% increase in the hazard of incidence of early AMD, and use of oral ?-blockers is associated with a 71% increase in the hazard of incident exudative AMD. If these findings are replicated, it may have implications for care of older adults because vasodilators and oral ?-blockers are drugs that are used commonly by older persons.
| S-EPMC4122609 | biostudies-literature
Project description:To examine the association of current cigarette smoking and pack-years smoked with the incidence and progression of age-related macular degeneration (AMD) and to examine the interactions of current smoking and pack-years smoked with complement factor H (CFH, rs1061170) and age-related maculopathy susceptibility 2 (ARMS2, rs10490924) genotype.A longitudinal population-based study of AMD in a representative American community. Examinations were performed every 5 years over a 20-year period.A total of 4439 participants in the population-based Beaver Dam Eye Study (BDES).Age-related macular degeneration status was determined from grading retinal photographs. Multi-state models were used to model the relationship of current smoking and pack-years smoked and interactions with CFH and ARMS2 with the incidence and progression of AMD over the entire age range.Incidence and progression of AMD over a 20-year period and interactions between current smoking and pack-years smoked with CFH and ARMS2 genotype.The incidence of early AMD over the 20-year period was 24.4%, and the incidence of late AMD was 4.5%. Current smoking was associated with an increased risk of transitioning from minimal to moderate early AMD. A greater number of pack-years smoked was associated with an increased risk of transitioning from no AMD to minimal early AMD and from severe early AMD to late AMD. Current smoking and a greater number of pack-years smoked were associated with an increased risk of death. There were no statistically significant multiplicative interactions between current smoking or pack-years smoked and CFH or ARMS2 genotype.Current smoking and a greater number of pack-years smoked increase the risk of the progression of AMD. This has important health care implications because smoking is a modifiable behavior.
| S-EPMC4177947 | biostudies-literature
Project description:ObjectiveTo describe how retinal venular diameter changes over time for an individual and to examine differences in these changes among people with different risk profiles.DesignPopulation-based cohort study.ParticipantsA total of 4600 persons aged 43 to 86 years from the Beaver Dam Eye Study (BDES) who participated in at least 1 examination and had venular diameter measured in the right eye.MethodsData from 4 examinations during a 15-year period were analyzed. Retinal venular diameter was measured from photographs at each examination by computer-assisted methods and summarized as the central retinal venular equivalent (CRVE). Associations of risk factors with concurrent CRVE measurements and changes in CRVE over time were determined using multivariate analyses.Main outcome measuresCentral retinal venular equivalent.ResultsThe CRVE tended to narrow with age. Mean CRVE was approximately 5 ?m smaller (225 vs. 230 ?m) for the average 70-year-old compared with the average 50-year-old, and was approximately 13 ?m smaller (217 vs. 230 ?m) for the average 85-year-old compared with the average 50-year-old. Male sex (beta estimate [?] = 5.24; 95% confidence interval [CI], 3.58-6.90), history of current cigarette smoking (? = 9.38; 95% CI, 8.26-10.49), and higher white blood cell (WBC) count (per 1000/?L: ? = 0.95; 95% CI, 0.74-1.16) were independently associated with larger concurrent CRVE, whereas higher mean arterial blood pressure (per 5 mmHg: ? = -0.36; 95% CI, -0.50 to -0.23) and higher serum high-density lipoprotein (HDL) cholesterol (per 10 mg/dl: ? = 0.89; 95% CI, -1.15 to -0.63) were independently associated with smaller concurrent CRVE. History of cardiovascular disease (CVD) (? = -0.16; 95% CI, -0.26 to -0.06) and presence of chronic kidney disease (CKD) (? = -0.20; 95% CI, -0.34 to -0.05) were associated with a greater decrease in CRVE over time.ConclusionsThese data show that retinal venular diameter tends to narrow with age; concurrent venular diameter is independently associated with sex, blood pressure, serum HDL cholesterol, WBC count, and history of current cigarette smoking; and change in CRVE is independently associated with a history of CVD and presence of CKD. The different independent effects of these interrelated factors on CRVE highlight the complex relationship between CRVE and systemic diseases and conditions and the difficulty in determining specific causes of change in CRVE over time.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.
| S-EPMC3508386 | biostudies-literature
Project description:Age-related maculopathy (ARM) is a leading cause of visual impairment among the elderly in Western populations. To identify ARM-susceptibility loci, we genotyped a subset of subjects from the Beaver Dam (WI) Eye Study and performed a model-free genomewide linkage analysis for markers linked to a quantitative measure of ARM. We initially genotyped 345 autosomal markers in 325 individuals (N=263 sib pairs) from 102 pedigrees. Ten regions suggestive of linkage with ARM were observed on chromosomes 3, 5, 6, 12, 15, and 16. Prior to fine mapping, the most significant regions were an 18-cM region on chromosome 12, near D12S1300 (P=.0159); a region on chromosome 3, near D3S1763, with a P value of.0062; and a 6-cM region on chromosome 16, near D16S769, with a P value of.0086. After expanding our analysis to include 25 additional fine-mapping markers, we found that a 14-cM region on chromosome 12, near D12S346 (located at 106.89 cM), showed the strongest indication of linkage, with a P value of.004. Three other regions, on chromosomes 5, 6, and 15, that were nominally significant at P< or =.01 are also appropriate for fine mapping.
| S-EPMC1180302 | biostudies-literature
Project description:PURPOSE:Refraction, as measured by spherical equivalent, is the need for an external lens to focus images on the retina. While genetic factors play an important role in the development of refractive errors, few susceptibility genes have been identified. However, several regions of linkage have been reported for myopia (2q, 4q, 7q, 12q, 17q, 18p, 22q, and Xq) and for quantitative refraction (1p, 3q, 4q, 7p, 8p, and 11p). To replicate previously identified linkage peaks and to identify novel loci that influence quantitative refraction and refractive errors, linkage analysis of spherical equivalent, myopia, and hyperopia in the Beaver Dam Eye Study was performed. METHODS:Nonparametric, sibling-pair, genome-wide linkage analyses of refraction (spherical equivalent adjusted for age, education, and nuclear sclerosis), myopia and hyperopia in 834 sibling pairs within 486 extended pedigrees were performed. RESULTS:Suggestive evidence of linkage was found for hyperopia on chromosome 3, region q26 (empiric P = 5.34 × 10(-4)), a region that had shown significant genome-wide evidence of linkage to refraction and some evidence of linkage to hyperopia. In addition, the analysis replicated previously reported genome-wide significant linkages to 22q11 of adjusted refraction and myopia (empiric P = 4.43 × 10(-3) and 1.48 × 10(-3), respectively) and to 7p15 of refraction (empiric P = 9.43 × 10(-4)). Evidence was also found of linkage to refraction on 7q36 (empiric P = 2.32 × 10(-3)), a region previously linked to high myopia. CONCLUSIONS:The findings provide further evidence that genes controlling refractive errors are located on 3q26, 7p15, 7p36, and 22q11.
| S-EPMC3176073 | biostudies-literature
Project description:PurposeTo describe visual impairment (VI) over a 20-year period and its associations with age-related eye diseases and socioeconomic factors in the Beaver Dam Eye Study.DesignPopulation-based cohort study.ParticipantsFour thousand nine hundred twenty-six persons 43 to 86 years of age participated in the baseline examination phase from 1988 through 1990, and 3721, 2962, 2375, and 1913 persons participated in follow-up examinations each spaced 5 years apart from 1993 through 1995, 1998 through 2000, 2003 through 2005, and 2008 through 2010, respectively.MethodsBest-corrected visual acuity after refraction, assessed by the Early Treatment Diabetic Retinopathy Study protocol.Main outcome measuresIncidence of VI, defined as best-corrected visual acuity of poorer than 20/40 in the better eye in persons with one or both eyes 20/40 or better at the beginning of a 5-year interval, and incidence of severe VI, defined as best-corrected visual acuity of 20/200 or worse in the better eye in persons with one or both eyes better than 20/200 at the beginning of a 5-year interval.ResultsOverall incidence of VI between examinations (5-year interval) was 1.4% (varying from 0.1% in persons 50-54 years of age to 14.6% in those 85 years of age and older), whereas for severe VI it was 0.4% (varying from 0.0% in persons 50-54 years of age to 6.9% in those ? 85 years of age). The incidence of VI decreased for each (2003-2005 to 2008-2010; odds ratio fourth interval vs. first interval, 0.53; 95% confidence interval, 0.32-0.87; P = 0.01 period after adjustment for age, from the first 5-year interval between examinations (1988-1990 to 1993-1995) to the fourth and most recent 5-year interval ). This period effect was no longer significant after adjustment for age-related macular degeneration. Age-related macular degeneration remained the leading cause of incident severe VI (54% of eyes with incident severe VI, which was as low as 40% and as high as 57% for specific visits), with no evidence of a trend across visits. The overall frequency of VI correctable with new refraction was 38% of all eyes with VI.ConclusionsThese data provide population-based estimates that show a high (15%) 5-year incidence of VI in persons 85 years of age and older. Age-related macular degeneration remained the leading cause of severe VI in this population over the 20 years of the study.Financial disclosure(s)The author(s) have no proprietary or commercial interest in any materials discussed in this article.
| S-EPMC3674166 | biostudies-literature
Project description:ObjectiveTo describe the relationships of risk alleles in complement factor H (CFH, rs1061170) and age-related maculopathy susceptibility 2 (ARMS2, rs10490924) to the incidence and progression of age-related macular degeneration (AMD) during a 20-year period.MethodsThere were 4282 persons aged 43 to 86 years at the baseline examination in 1988-1990 enrolled in a population-based cohort study who participated in at least 1 examination spaced 5 years apart during a 20-year period and had gradable fundus photographs for AMD and genotype information on CFH and ARMS2. Low, intermediate, and high genetic risk for AMD was defined by the presence of 0 to 1, 2, or 3 to 4 risk alleles for CFH and ARMS2, respectively. Multistate models were used to estimate the progression of AMD throughout the entire age range.ResultsThere were 2820 (66%), 1129 (26%), and 333 persons (8%) with low, intermediate, and high genetic risk for AMD, respectively. The 5-year incidences of early and late AMD were 9.1% and 1.6%, respectively, and increased with age but did not differ significantly by sex. Using the multistate model, of persons aged 45 years with no AMD in the low, intermediate, and high AMD genetic risk groups, 33.0%, 39.9%, and 46.5%, respectively, were estimated to develop early AMD, and 1.4%, 5.2%, and 15.3% were estimated to develop late AMD by age 80 years.ConclusionsThese population-based data provide estimates of the long-term risk of the incidence and progression of AMD and its lesions by age and genetic risk alleles for CFH and ARMS2. They also show that when early AMD is present, knowing the phenotype contributes more to risk assessment than knowing the genetic risk based on these 2 AMD genes.
| S-EPMC3602927 | biostudies-literature