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Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study.

ABSTRACT: Age-related cataracts are one of the leading causes of visual impairment and blindness among the elderly worldwide. Among age-related cataracts, cortical opacities rank as the second most common type; however, little is known about their molecular pathogenesis or genetics. To identify susceptibility loci for cortical cataracts, we genotyped a subset of families (102 families; n = 224 sib pairs) from the Beaver Dam Eye Study and performed a model-free genome-wide linkage analysis for markers linked to a quantitative measure of cortical opacity. We obtained evidence for linkage at marker D1S1622 on chromosome 1p35 (P < 0.0002) and at marker D6S1053 on 6q12 (P < 0.00008) in the initial scan. Five additional regions on 1q31, 2p24, 2q11, 4q28, and 15q13 that are suggestive of linkage (P < or = 0.01 or logarithm of the likelihood ratio > or = 1.18) were observed. The region on chromosomes 6p12-q12 was selected for fine mapping, and the intermarker distance was reduced to 3 cM by adding 11 markers in the interval between D6S1017 and D6S1021. After fine mapping, significant evidence of linkage remained on chromosome 6p12-q12 at D6S1053 (P < 0.00005). The current genome scan for age-related cortical cataracts may lead to identification of novel genes, because few regions identified in the current scan have previously been implicated in congenital or age-related cataracts.

SUBMITTER: Iyengar SK

PROVIDER: S-EPMC521942 | biostudies-literature | 2004 Oct

REPOSITORIES: biostudies-literature

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Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study.

Iyengar Sudha K SK Klein Barbara E K BE Klein Ronald R Jun Gyungah G Schick James H JH Millard Christopher C Liptak Rachel R Russo Karlie K Lee Kristine E KE Elston Robert C RC

Proceedings of the National Academy of Sciences of the United States of America 20040927 40

Age-related cataracts are one of the leading causes of visual impairment and blindness among the elderly worldwide. Among age-related cataracts, cortical opacities rank as the second most common type; however, little is known about their molecular pathogenesis or genetics. To identify susceptibility loci for cortical cataracts, we genotyped a subset of families (102 families; n = 224 sib pairs) from the Beaver Dam Eye Study and performed a model-free genome-wide linkage analysis for markers link ...[more]

PMID: 15452352

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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.

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.

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.

Dataset Information

Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study.

Publications

Identification of a major locus for age-related cortical cataract on chromosome 6p12-q12 in the Beaver Dam Eye Study.

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