Biomedical subjects

Kristine E Lee

Publications and source records attributed to Kristine E Lee.

At least 19 recordsLinked to original sources

PubMed2026

Upper airway microbiome interacts with GSDMB and ORMDL3 asthma risk SNPs to influence early-life wheeze risk.

BACKGROUND: Single-nucleotide polymorphisms (SNPs) in the chromosome 17q12-q21 region and, independently, early-life nasal microbiota dominated by Moraxella, Streptococcus, or Haemophilus (MSH) increase risk of chronic wheeze and asthma development. OBJECTIVE: We sought to determine whether 17q12-q21 risk SNPs and nasal microbiota interact to modulate childhood wheeze risk. METHODS: Nasal wash samples from 12-month-old infants in 2 birth cohorts, COAST (Childhood Origins of Asthma; n = 180) and URECA (Urban Environment and Childhood Asthma; n = 139), underwent 16S ribosomal RNA variable region 4 sequencing. Nasal microbiota dominated by MSH or Corynebacterium, Dolosigranulum, Staphylococcus, or Bacillus (CDSB) were assessed. Paired blood was genotyped for 9 17q12-q21 risk SNPs. Logistic regression tested interactions between 17q12-q21 SNPs and MSH or CDSB on wheeze risk in the first 3 years of life. A549 lung epithelial cells, CRISPR-edited to encode the rs7216389 risk genotype (rs7216389TT) were compared to the heterozygous (rs7216389CT) line using bulk RNA sequencing. RESULTS: SNPs, particularly those in the ORMDL3 (rs8076131; odds ratio [OR]: 1.72; 95% CI: 1.09-2.71; Pint = .031) and GSDMB (rs2305480; OR: 1.72; 95% CI: 1.09-2.71; Pint = 0.042; and rs7216389; OR: 1.73; 95% CI: 1.09-2.70; Pint = .047) genes, interact with MSH microbiota to increase early-life wheeze risk (false discovery rate Pint = .016 for all), while interactions with CDSB reduce risk. A549 airway epithelial cells homozygous for rs7216389TT exhibited decreased expression of genes involved in antimicrobial responses and neutrophil recruitment and evidence increased microbial adherence compared with the heterozygous cell line. CONCLUSION: Airway microbiota interact with SNPs at the 17q12-q21 locus in genes involved in sphingolipid metabolism and intracellular antimicrobial responses, to modulate wheeze risk.

Humans↗

PubMed2007

Identification of novel genetic loci for intraocular pressure: a genomewide scan of the Beaver Dam Eye Study.

OBJECTIVE: To identify genetic loci that control intraocular pressure (IOP). METHODS: We performed a genomewide scan of IOP, using 486 pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study. Linkage analysis was performed using the modified Haseman-Elston regression models and variance components linkage analysis. RESULTS: Seven regions of interest were identified on chromosomes 2, 5, 6, 7, 12, 15, and 19. The novel linkage region on chromosome 19p had an empirical multipoint P value of 6.1 x 10(-5). Two of the regions (2 and 19) were especially interesting since each has been identified as a potential linkage region for blood pressure. CONCLUSIONS: The results of this genomewide scan provide evidence that a quantitative trait locus may influence elevated IOP and may colocalize with blood pressure loci. These loci may control systemic pressure reflected in the eye and vascular system. CLINICAL RELEVANCE: Glaucoma is a leading cause of blindness in the world, and the identification of genes that contribute to this disease is essential. Elevated IOP is a principal risk factor for primary open-angle glaucoma and an intriguing quantitative trait that may strongly influence the development of disease.

Adult↗

PubMed2007

Confirmation of linkage to ocular refraction on chromosome 22q and identification of a novel linkage region on 1q.

OBJECTIVE: To localize genes influencing ocular refraction in subjects in the Beaver Dam Eye Study. Previous studies establish that myopia clusters within families and linkage to myopia has been demonstrated on 2q, 4q, 12q, 17q, 18q, 22q, and Xq. Few studies have examined genetic effects across the entire range of refraction, though linkages to 1p, 3q, 4q, 8p, and 11p have been reported, and our previous analysis of the Beaver Dam Eye Study demonstrated substantial heritability for refraction (68%). METHODS: We conducted nonparametric sibling-pair and genome-wide linkage analyses on spherical equivalent adjusting for age, education, and nuclear sclerosis, in 834 sibling pairs in 486 extended pedigrees. RESULTS: We identified a novel region of suggestive linkage on 1q (multipoint, P<.00019) and replicated the 22q region (multipoint, P = .0033) previously linked to myopia. Additionally, there was some evidence of linkage to 7p (multipoint, P = .0023). CONCLUSION: Refraction is a complex trait influenced by both genes and environment. Our work confirms a previously reported linkage region on 22q and identifies 2 novel regions of linkage on 1q and 7p. CLINICAL RELEVANCE: Further, genetic research is needed to finemap this trait to identify the causative gene. Modifying the actions of such a gene might lead to a reduction in the risk of refractive error.

Adult↗

PubMed2007

Association of retinal vessel caliber to optic disc and cup diameters.

PURPOSE: To investigate whether optic disc size is related to retinal venule and arteriole diameters. METHODS: The population of Beaver Dam, Wisconsin, aged 43 to 86 years were invited to participate in a baseline examination from 1988 to 1990. During this examination, photographs, centered on the optic discs, were taken after pupil dilation. Optic discs and cups were measured from stereoscopic photographs, whereas retinal vessel measurements were taken from a single digitized photograph. Central retinal vein and central retinal arterial equivalents were subsequently calculated. Data for 3887 right eyes are included in the analyses. RESULTS: Narrower retinal venules and arterioles were found in the smaller optic discs controlling for optic cup diameter as well as age, systolic and diastolic blood pressure, refraction, and sex. Central retinal artery equivalents ranged from 156.04 +/- 16.82 microm in the smallest optic disc category to 165.93 +/- 15.17 microm in the larger disc category (P < 0.001). Central retinal vein equivalents ranged from 228.93 +/- 21.26 microm in the smallest to 243.18 +/- 22.32 microm in the larger disc categories (P < 0.001). The significant reduction in retinal vessel diameters was only apparent for the smallest optic disc sizes. A reduction in retinal vessel diameters was less consistent and not significant for small optic cup sizes. CONCLUSIONS: Smallest optic discs were associated with smaller central retinal artery and central retinal vein diameters. This anatomic relationship may be useful as an additional associated indicator for nonarteritic anterior ischemic optic neuropathy as well as for retinal vascular events.

Adult↗

PubMed2006

Statin use and incident nuclear cataract.

CONTEXT: Statins are widely prescribed for their lipid-lowering effects but also have putative antioxidant properties. Oxidative stress is believed to play a role in the development of nuclear cataract, but little is known regarding the relationship of statin use and cataract incidence. OBJECTIVE: To evaluate the relationship of use of statins and incident cataract in adults in a midwestern community in the United States. DESIGN, SETTING, AND PARTICIPANTS: The Beaver Dam Eye Study, an observational, longitudinal, population-based study of age-related eye disease in Beaver Dam, Wis. There were 1299 persons who were seen at the third examination in 1998-2000, had gradable photographs in both eyes, and were deemed to be at risk of developing nuclear cataract within 5 years. MAIN OUTCOME MEASURE: Five-year incidence of cataract with respect to statin use. Cataracts were graded from photographs taken through the participant's dilated pupil. RESULTS: A total of 210 persons developed incident nuclear cataract in the interval from 1998-2000 to 2003-2005. Five-year incidence of nuclear cataract was 12.2% in statin users compared with 17.2% in nonusers (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.36-0.84), controlling for age. When only never smokers without diabetes were assessed, the age-, lipid level-, and sex-adjusted OR was 0.40 (95% CI, 0.18-0.90). Five-year incidence of cortical cataract was 9.9% in statin users and 7.5% in nonusers (OR, 1.28; 95% CI, 0.79-2.08); posterior subcapsular cataract occurred in 3.0% of statin users and 3.4% of nonusers (OR, 0.82; 95% CI, 0.39-1.71). CONCLUSION: Statin use in a general population appears to be associated with lower risk of nuclear cataract, the most common type of age-related cataract.

Adult↗

PubMed2006

Genome-wide linkage study of retinal vessel diameters in the Beaver Dam Eye Study.

Retinal vessels can be observed noninvasively and provide a window to microvascular systems elsewhere in the body. Generalized retinal arteriolar narrowing can represent structural changes resulting from persistent high blood pressure. However, data from recent studies also suggest that generalized retinal arteriolar narrowing might precede hypertension and contribute to its pathogenesis. To determine whether vessel diameters in the eye are genetically determined, we conducted a genome-wide linkage scan on retinal vessel diameters (central retinal artery equivalent and central retinal vein equivalent) using data from the Beaver Dam Eye Study. There were 7 regions on 5 chromosomes (3q28, 5q35, 7q21, 7q32, 11q14, 11q24, and 17q11) showing linkage signals at the nominal multipoint significance level of 0.01 for either covariate-unadjusted or -adjusted central retinal artery equivalent; there were 7 regions on 6 chromosomes (1p36, 6p25, 6q14, 8q21, 11p15, 13q34, and 14q21) showing linkage signals at the nominal multipoint significance level of 0.01 for either covariate-unadjusted or -adjusted central retinal vein equivalent. The linkage results for retinal vessel diameters indicate genetic contributions that remain significant even after adjusting for hypertension and other covariates. In summary, we provide evidence demonstrating that genetic factors independent of hypertension affect retinal vessel diameters.

Adult↗

PubMed2006

Markers of inflammation, vascular endothelial dysfunction, and age-related cataract.

PURPOSE: To examine the associations of systemic markers of inflammatory disease and vascular endothelial dysfunction with three types of age-related cataract. DESIGN: Cross-sectional analyses of data from a population-based sample of adults. METHODS: Standardized protocols for blood collection, measurement of markers, administration of a questionnaire, and grading of lens photographs to determine cataract were used. Univariable and multivariable analyses were performed. SETTINGS: Cohort in Beaver Dam, Wisconsin. STUDY POPULATION: A random sample of 396 persons who were > or =50 years of age. MAIN OUTCOME MEASURE: Prevalent age-related nuclear, cortical, and posterior subcapsular cataract. RESULTS: Interleukin-6 and intracellular adhesion molecule-1 were associated significantly with prevalent nuclear cataract (odds ratio for each quartile, 1.45 and 2.17, respectively). Many of the associations of markers with cataract types were not linear. There were no significant associations between the markers and cortical or posterior subcapsular cataract. CONCLUSION: Two serum markers of systemic inflammation and vascular endothelial dysfunction were associated with nuclear cataract.

Adult↗

PubMed2006

Comparability of cup and disk diameters measured from nonstereoscopic digital and stereoscopic film images.

PURPOSE: To compare gradings of optic disk and cup diameters from stereoscopic film and nonstereoscopic digital images. DESIGN: Comparison of techniques. METHODS: setting: CLINIC-BASED. PATIENT POPULATION: Right eyes of 62 adults. observation procedures: Images of the disk were taken through pharmacologically dilated pupils with a 45-degree digital camera (6.3 megapixels) and with a stereoscopic 30-degree film camera. Measurements were taken for vertical diameters of optic disks and cups. MAIN OUTCOME MEASURES: Agreement of disk and cup measurements and cup to disk ratios. RESULTS: Optic disks and cups were slightly smaller when graded from the stereoscopic film images. Cup-to-disk ratios were similar. Correlations between film and digital images measurements were high. CONCLUSIONS: Measurements taken from nonstereoscopic digital images through a dilated pupil were similar to those taken from stereoscopic film images. Lack of stereoscopic effect may lead to small differences in measuring the optic disk and cup diameters. Nonstereoscopic digital imaging may be useful in epidemiologic studies when measures of optic cups and disks are needed.

Humans↗

PubMed2006

Changes in visual acuity in a population over a 15-year period: the Beaver Dam Eye Study.

PURPOSE: To describe the change in visual acuity in a 15-year period. DESIGN: Population-based study. METHODS: setting: Beaver Dam, Wisconsin. participants: 4068 persons 43 to 86 years of age at the time of a baseline examination in 1988 to 1990, and with follow-up examinations every five years thereafter. observation procedures: Best-corrected visual acuity after refraction, assessed by a modification of the ETDRS protocol. main outcome measure: Doubling of the visual angle; incidence of visual impairment. RESULTS: Eight percent of the population developed impaired vision (20/40 or worse), 0.8% developed severe visual impairment (20/200 or worse), 7% had doubling of the visual angle, and 2% had improved vision. People 75 years of age or older at baseline were more likely to develop impaired vision (odds ratio [OR] 12.8, 95% confidence interval [CI] 9.6 to 17.1, P < .001), doubling of the visual angle (OR 7.8, 95% CI 5.6 to 10.7, P < .001), and severe visual impairment (OR 20.6, 95% CI 9.5 to 44.8, P<0.001) compared with people younger than 75 years of age. CONCLUSIONS: These data provide population-based estimates of the cumulative 15-year incidence of loss of vision over a wide spectrum of ages. In people 75 years of age or older the cumulative incidence of visual impairment accounting for the competing risk of death is 25%, of which 4% is severe, indicating a public health problem of considerable proportions as the US population in this age is expected to increase by 55% from 18 million in the year 2005 to 28 million by the year 2025.

Adult↗

PubMed2005

Meta-analysis of genome scans of age-related macular degeneration.

A genetic contribution to the development of age-related macular degeneration (AMD) is well established. Several genome-wide linkage studies have identified a number of putative susceptibility loci for AMD but only a few of these regions have been replicated in independent studies. Here, we perform a meta-analysis of six AMD genome screens using the genome-scan meta-analysis method, which allows linkage results from several studies to be combined, providing greater power to identify regions that show only weak evidence for linkage in individual studies. Results from non-parametric analysis for a broad AMD clinical phenotype (including two studies with quantitative traits) were extracted. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to maximum evidence for linkage within each bin. Bin ranks were weighted according to study size and summed across all studies; the summed rank (SR) for each bin was assessed empirically for significance using permutation methods. A high SR indicates a region with consistent evidence for linkage across studies. The strongest evidence for an AMD susceptibility locus was found on chromosome 10q26 where genome-wide significant linkage was observed (P=0.00025). Several other regions met the empirical significance criteria for bins likely to contain linked loci including adjacent pairs of bins on chromosomes 1q, 2p, 3p and 16. Several of the regions identified here showed only weak evidence for linkage in the individual studies. These results will help prioritize regions for future positional and functional candidate gene studies in AMD.

Aging↗

PubMed2005

Polygenic effects and cigarette smoking account for a portion of the familial aggregation of nuclear sclerosis.

Cataract is the most common cause of blindness worldwide. Nuclear cataract, an advanced stage of nuclear sclerosis, is the most common type of age-related cataract. The authors assessed data from 2,089 persons within 620 extended pedigrees who participated in the 1988-1990 Beaver Dam Eye Study in Wisconsin to determine whether the observed familial aggregation of nuclear sclerosis could be explained by inheritance of a major gene. Familial correlations were examined and segregation analyses were performed on nuclear sclerosis measurements adjusted for age, sex, and pack-years of cigarette smoking. There was modest correlation among close family members after adjustment for age, sex, and pack-years of cigarette smoking: 0.084 between parents and offspring, and 0.198 between sibling pairs. Although results do not support involvement of a single major locus in the etiology of nuclear sclerosis, models that allowed for familial correlation, attributable in part to polygenic effects, did provide a better fit to the observed data than models without a polygenic effect. This finding suggests that several genes of modest effect may influence development of nuclear lens opacity, possibly in conjunction with environmental factors. Cigarette smoking was an important covariate in these analyses. Overall, results highlight the complex etiology of nuclear sclerosis.

Adult↗

PubMed2005

Frailty, morbidity and survival.

Frailty, as a reflection of decreased physical reserve rather than disability, is assessed by various functional tests rather than by specific disease burden. We investigated association of measures of frailty to disease outcomes and survival in a population-based study of Midwestern adults. The markers of frailty we evaluated were: time to walk a measured course (gait-time), handgrip strength, peak respiratory flow rate, ability to stand from a sitting position without using arms, and best corrected visual acuity. A history of cardiovascular disease, cancer, and hypertension were obtained. Data were collected at the third examination (1998--2000) of the Beaver Dam Eye Study cohort (n=2962). Follow-up for mortality occurred up to 412 years after the 1998--2000 examinations. Markers of frailty were significantly associated with age. Values in the highest quartile (slowest) of gait-time, lowest quartile of peak expiratory flow rate, lowest quartile of handgrip strength, inability to stand from sitting in one try (those not in a wheelchair), and visual impairment were combined in an index to denote a general description of frailty. The range of the index was 0 (no frailty) to 5 (maximum frailty). Greater frailty was significantly associated with cardiovascular disease and hypertension. Frailty was associated with poorer survival over an interval of 412 years after adjusting for age, sex, hypertension, diabetes, and cardiovascular disease. Greater frailty was associated with greater likelihood of concurrent medical conditions and with decreased survival.

Aged↗

PubMed2005

Age-related eye disease, quality of life, and functional activity.

OBJECTIVE: To examine the associations of measures of quality of life (Medical Outcomes Study Short Form Health Survey) and functional activities (activities of daily living, instrumental activities of daily living, and visual function) in persons with and without age-related eye diseases. METHODS: Two thousand, six hundred seventy persons participated in the 1998 through 2000 examinations of both the Beaver Dam Eye Study and the Epidemiology of Hearing Loss Study. Age-related eye disease (age-related maculopathy, cataract, diabetic retinopathy, glaucoma, macula edema, occlusions, amblyopia, and macular holes) were assessed by fundus, slitlamp, and retroilluminated photographs and self-reported ocular history. Also administered was a standard interview that included the Medical Outcomes Study Short Form Health Survey, activities of daily living, instrumental activities of daily living, and visual function questionnaires and information on other medical conditions. RESULTS: After controlling for age and sex, we found that persons with an age-related eye disease had decreased scores in almost all the domains of the Medical Outcomes Study Short Form Health Survey, and persons with eye disease in both eyes had poorer scores than persons with eye disease in only 1 eye. Stratifying by age-related maculopathy and central cataract yielded similar results. Further adjustment for current visual acuity and the number of comorbid conditions explained most associations. Several of the mental scales were still marginally significantly lower (P<.10) in persons with age-related maculopathy after adjustment. Persons with an age-related eye disease were not more likely to have impaired activities of daily living or instrumental activities of daily living. After adjustment for current visual acuity and number of comorbidities, persons who had trouble reading small print or recognizing people across the street were more likely to have an age-related eye disease. Otherwise, there were no significant associations with the visual function questions and any of the specific ocular conditions. CONCLUSIONS: Many measures of general quality of life and functional activities were related to age-related eye diseases, but few associations remained significant after adjustments for vision and other comorbidities. Our data are compatible with the notion that decreased visual function, irrespective of the pathologic reason for the decrease, is associated with diminished quality of life and functional activities of living.

Activities of Daily Living↗

PubMed2005

Detecting progression of nuclear sclerosis by using human grading versus semiautomated computer grading.

PURPOSE: To assess indices of nuclear sclerosis derived from digitized images made from color (slide) photographs. METHODS: Film-based slit lamp images taken at baseline and at 5- and 10-year follow-up examinations of the Beaver Dam Eye Study cohort were digitized, and optical traces were taken along an axis through the center of the cornea and lens. Four indices of the severity of sclerosis were calculated based on the optical densities. The associations of the original Beaver Dam grades and these indices to age, vision, and change in severity of sclerosis over two subsequent visits were compared. RESULTS: At baseline photographs, the Spearman correlation between age and severity was 0.65 for the original film-based grading (n = 4518 right eyes) and varied between 0.46 and 0.71 for the measures from digitized images. Correlations of the indices to visual acuity were 0.38 for the film-based grading and ranged from 0.32 to 0.38 for the other indices. The authors assume that nuclear sclerosis does not regress and the percentage of regression is a reflection of error in grading. The percentage of regression and progression of sclerosis over 5- and 10-year intervals was determined for each index. After 5 years, 48.2% progressed and 4.9% regressed, using the Beaver Dam grades; progression occurred in 4.9% to 9.9%, and regression occurred in 4.5% to 7.0% for the other indices. After 10 years, 61.9% progressed and 3.2% regressed using the Beaver Dam grades; progression occurred in 8.0% to 19.7%, and regression occurred in 2.6% to 9.7% for the other indices. CONCLUSIONS: Semiautomated grading of the digitized images can be used to process thousands of images with little oversight by a trained grader. Indices of sclerosis that closely parallel human grading in their relationships to age and visual acuity can be easily computed. However, the indices appear to identify significantly less progression of nuclear sclerosis than does human grading. Further development to define a useful metric for identifying severity and progression of nuclear sclerosis is needed.

Adult↗

PubMed2005

A genetic contribution to intraocular pressure: the beaver dam eye study.

PURPOSE: To investigate a potential genetic contribution to intraocular pressure (IOP), we performed a complex segregation analysis on 2337 individuals in 620 extended pedigrees ascertained through a population-based cohort, the Beaver Dam Eye Study (BDES). IOP is a principal risk factor for primary open-angle glaucoma (POAG) a leading cause of blindness worldwide. METHODS: Segregation analysis is an analytical method that provides statistical evidence supporting the involvement of a major gene or polygenes in a particular phenotype. Detailed medical histories and eye examinations were performed on all participants. From the two eyes, the higher IOP measurement was used as a continuous trait after adjustment for covariates. A genome-wide scan (GWS) using affected sib pair linkage analysis was performed on 218 sibling pairs. RESULTS: In this segregation analysis the model that allowed for an unmeasured major environmental effect plus a polygenic/multifactorial effect provided the best fit and was the most parsimonious model. The lack of an adequate fit for the Mendelian single-gene models is consistent with a multifactorial model of inheritance that may include multiple genes and environmental factors that contribute to IOP. The results of the GWS yielded two novel loci as potential linkage regions for IOP on chromosomes 6 (P = 0.008) and 13 (P = 0.0007). Neither of these regions has previously been identified in GWS of POAG. CONCLUSIONS: The segregation and familial correlation analyses of IOP suggest a polygenetic component with environmental influences. The pilot linkage study further confirms the heterogeneity of IOP with the identification of two novel genetic loci.

Adult↗

PubMed2005

Support for polygenic influences on ocular refractive error.

PURPOSE: Refractive errors, myopia, and hyperopia are common conditions requiring corrective lenses. The familial clustering of myopia has been well established. Several chromosomal regions have been linked to high myopia (12q, 17q, and 18q), to quantitative refraction among twins (3q, 4q, 8p, and 11p), and to families with moderate myopia (22q). This study examined the familial aggregation and pattern of inheritance of ocular refraction in an adult population, by using data from the Beaver Dam Eye Study. METHODS: Familial correlations were examined and segregation analysis was performed on the average refractive error measurements in the right and left eyes after adjustment for age, sex, and education. Analyses were based on 2138 individuals in 620 extended pedigrees with complete data on age, sex, education, and spherical equivalent. RESULTS: Substantial positive correlation was found between siblings (0.33), parents and offspring (0.17), and cousins (0.10) and lower correlation among avuncular pairs (0.08) after adjustment for age, sex, and years of education. The results of this segregation analysis do not support the involvement of a single major locus throughout the entire range of refractive error. However, models allowing for familial correlation, attributable in part to polygenic effects, provided a better fit to the observed data than models without a polygenic component, suggesting that several genes of modest effect may influence refractive error, possibly in conjunction with environmental factors. CONCLUSIONS: These results support the involvement of genetic factors in the etiology of refractive error and are consistent with reports of linkage to multiple regions of the genome.

Family Health↗

PubMed2005

Genome-wide analyses demonstrate novel loci that predispose to drusen formation.

PURPOSE: To test whether genes for drusen formation are independent of age-related macular degeneration (AMD) pathogenesis. METHODS: A genome-wide model-free linkage analysis was performed, using two semiquantitative drusen traits, size and type, on two sets of data: (1) 325 individuals (225 sib pairs) from the Beaver Dam Eye Study (BDES), and (2) 297 individuals (346 sib pairs) from the Family Age Related Maculopathy Study (FARMS). Apolipoprotein E (APOE) genotypes were used as a covariate in a multipoint sibpair analysis. RESULTS: The authors found evidence of linkage on 19q13.31 (D19S245), with size of drusen in both the BDES (P = 0.0287) and the FARMS (P = 0.0013; P = 0.0005, combined). In the BDES, type showed linkage evidence on 3p24.3 (D3S1768; P = 0.0189) and 3q25.1 (D3S2404; P = 0.0141); the linkage on 3p24.3 was also found with size (D3S1768; P = 0.0264). In the FARMS, size showed evidence of linkage at 5q33.3 (D5S820; P = 0.0021), 14q32.33 (D14S1007; P = 0.0013), and 16p13.13 (D16S2616; P = 0.0015) and type at 21q21.2 (D21S2052; P = 0.0070). For size in the FARMS, there was a small increase in P-value at marker D19S245 from 0.0044 to 0.0111, and from 0.0044 to 0.0064, when the epsilon4-carrier and the epsilon3-carrier genotype were the covariates, respectively. CONCLUSIONS: The results show that APOE effects may be mediated early in the progression of ARM to AMD and thus may not be detected by standard genome scans for more severe disease.

Adult↗

PubMed2004

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

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.

Age Factors↗