@article {718, title = {Early age-related maculopathy in the cardiovascular health study.}, journal = {Ophthalmology}, volume = {110}, year = {2003}, month = {2003 Jan}, pages = {25-33}, abstract = {

OBJECTIVE: To describe the prevalence of early age-related maculopathy (ARM) and its relation to atherosclerosis, lipids, hypertension, and inflammatory factors in a population studied for cardiovascular disease risk factors and outcomes.

DESIGN: Population-based cohort study.

PARTICIPANTS: A biracial population of 2361 adults (ranging from 69-97 years of age; 1998 whites and 363 blacks) living in four US counties (Allegheny County, Pennsylvania; Forsyth County, North Carolina; Sacramento County, California; and Washington County, Maryland) were examined during the interval from 1997 to 1998.

METHODS: Drusen and other lesions typical of ARM were identified by examining a 45 degrees color fundus photograph of one eye of each participant and classified by means of a modification of the Wisconsin Age-Related Maculopathy Grading System.

MAIN OUTCOME MEASURES: Early ARM.

RESULTS: Early ARM was present in 15.5\% and late ARM in 1.3\% of the cohort. The overall prevalence of any ARM was lower in blacks (9.1\%) compared with whites (18.2\%). While controlling for age, race, gender, and total calories consumed in the diet, factors associated with ARM were cerebral white matter disease as detected by magnetic resonance imaging (odds ratio [OR], 1.50; 95\% confidence interval [CI], 1.05, 2.16, P = 0.027), and lower serum total cholesterol (OR, per 10 mg/dl increase 0.95; 95\% CI, 0.91, 0.98, P = 0.02). There were no associations between hypertension, blood pressure, common carotid artery plaque, or any systemic inflammatory factors studied and early ARM.

CONCLUSIONS: This population-based study documents the higher prevalence of ARM in whites compared with blacks. Although an association was found between signs of white matter disease and early ARM, there was no evidence of an association of ARM with either hypertension or inflammatory factors.

}, keywords = {African Continental Ancestry Group, Aged, Aged, 80 and over, Arteriosclerosis, Blood Pressure, C-Reactive Protein, California, Cohort Studies, Diet, European Continental Ancestry Group, Female, Humans, Hypertension, Leukocyte Count, Longitudinal Studies, Macular Degeneration, Male, Mid-Atlantic Region, North Carolina, Prevalence, Prospective Studies, Risk Factors, Serum Albumin}, issn = {0161-6420}, doi = {10.1016/s0161-6420(02)01565-8}, author = {Klein, Ronald and Klein, Barbara E K and Marino, Emily K and Kuller, Lewis H and Furberg, Curt and Burke, Gregory L and Hubbard, Larry D} } @article {826, title = {Cardiovascular risk factors for retinal vein occlusion and arteriolar emboli: the Atherosclerosis Risk in Communities \& Cardiovascular Health studies.}, journal = {Ophthalmology}, volume = {112}, year = {2005}, month = {2005 Apr}, pages = {540-7}, abstract = {

OBJECTIVE: To examine the associations of retinal vein occlusion and arteriolar emboli with cardiovascular disease.

DESIGN: Population-based cross-sectional study.

PARTICIPANTS: Pooled from the Atherosclerosis Risk in Communities Study (n = 12,642; mean age, 60 years) and the Cardiovascular Health Study (n = 2824; mean age, 79 years).

METHODS: Retinal vein occlusion and arteriolar emboli were identified from a single nonmydriatic retinal photograph using a standardized protocol. Photographs were also graded for arteriovenous nicking and focal arteriolar narrowing. All participants had a comprehensive systemic evaluation, including standardized carotid ultrasonography.

MAIN OUTCOME MEASURES: Retinal vein occlusion and arteriolar emboli.

RESULTS: Prevalences of retinal vein occlusion and arteriolar emboli were 0.3\% (n = 39 cases) and 0.2\% (n = 34 cases), respectively. After adjusting for age, retinal vein occlusion was associated with hypertension (odds ratio [OR], 2.96; 95\% confidence interval [CI], 1.43-6.14), systolic blood pressure (BP) (OR, 4.12; 95\% CI, 1.40-12.16; highest quartile vs. lowest), diastolic BP (OR, 2.64; 95\% CI, 1.07-6.46; highest quartile vs. lowest), carotid artery plaque (OR, 5.62; 95\% CI, 2.60-12.16), body mass index (OR, 3.88; 95\% CI, 1.23-12.18; highest quartile vs. lowest), plasma fibrinogen (OR, 3.29; 95\% CI, 1.08-10.02; highest quartile vs. lowest), arteriovenous nicking (OR, 4.09; 95\% CI, 2.00-8.36), and focal arteriolar narrowing (OR, 5.17; 95\% CI, 2.59-10.29). After adjusting for age, retinal arteriolar emboli were associated with hypertension (OR, 3.14; 95\% CI, 1.44-6.84), systolic BP (OR, 3.46; 95\% CI, 1.13-10.65; highest quartile vs. lowest), prevalent coronary heart disease (OR, 2.33; 95\% CI, 1.01-5.42), carotid artery plaque (OR, 4.62; 95\% CI, 1.85-11.57), plasma lipoprotein (a) (OR, 3.69; 95\% CI, 1.20-11.41; highest quartile vs. lowest), plasma fibrinogen (OR, 3.09; 95\% CI, 0.98-9.76; highest quartile vs. lowest), and current cigarette smoking (OR, 3.08; 95\% CI, 1.47-6.47). Approximately a quarter of participants with retinal vein occlusion and arteriolar emboli had evidence of carotid artery plaque as defined from ultrasound.

CONCLUSIONS: Retinal vein occlusion and retinal arteriolar emboli are associated with carotid artery disease, hypertension, and other cardiovascular risk factors.

}, keywords = {Aged, Aged, 80 and over, Arterioles, Blood Pressure, Cardiovascular Diseases, Carotid Stenosis, Coronary Artery Disease, Cross-Sectional Studies, Embolism, Female, Fibrinogen, Humans, Hypertension, Lipoprotein(a), Male, Meta-Analysis as Topic, Middle Aged, Retinal Artery, Retinal Vein Occlusion, Risk Factors}, issn = {1549-4713}, doi = {10.1016/j.ophtha.2004.10.039}, author = {Wong, Tien Yin and Larsen, Emily K Marino and Klein, Ronald and Mitchell, Paul and Couper, David J and Klein, Barbara E K and Hubbard, Larry D and Siscovick, David S and Sharrett, A Richey} } @article {935, title = {Apolipoprotein e gene and age-related maculopathy in older individuals: the cardiovascular health study.}, journal = {Arch Ophthalmol}, volume = {125}, year = {2007}, month = {2007 Jan}, pages = {68-73}, abstract = {

OBJECTIVE: To examine the association between the apolipoprotein E (APOE) gene and age-related maculopathy (ARM) in an older population.

METHODS: Two thousand one hundred seventy persons 65 years and older sampled from 4 US communities had ARM signs assessed from retinal photographs using a modified Wisconsin Age-Related Maculopathy Grading System. DNA extracted from blood samples was analyzed for common APOE alleles.

RESULTS: After controlling for age, sex, cigarette smoking, and other factors, white participants carrying the epsilon2 allele had an increased risk of late ARM (odds ratio, 2.53 [95\% confidence interval, 1.08-5.90]) while carriers of the epsilon4 allele had a lower risk of late ARM (odds ratio, 0.69 [95\% confidence interval, 0.19-2.50]). There were too few late ARM cases in African American individuals for analysis.

CONCLUSION: APOE polymorphism is associated with late ARM in older white persons 65 years and older. Consistent with previous studies, the APOE epsilon2 allele is associated with a significant increased risk of late ARM development, whereas the epsilon4 allele may confer some protection.

}, keywords = {African Americans, Aged, Aged, 80 and over, Alleles, Apolipoprotein E2, Apolipoprotein E3, Apolipoprotein E4, Cardiovascular Diseases, European Continental Ancestry Group, Female, Genotype, Humans, Macular Degeneration, Male, Odds Ratio, Polymorphism, Genetic, Risk Factors}, issn = {0003-9950}, doi = {10.1001/archopht.125.1.68}, author = {Tikellis, Gabriella and Sun, Cong and Gorin, Michael B and Klein, Ronald and Klein, Barbara E K and Larsen, Emily K Marino and Siscovick, David S and Hubbard, Larry D and Wong, Tien Y} } @article {949, title = {Are microvascular abnormalities in the retina associated with depression symptoms? The Cardiovascular Health Study.}, journal = {Am J Geriatr Psychiatry}, volume = {15}, year = {2007}, month = {2007 Apr}, pages = {335-43}, abstract = {

OBJECTIVE: Depression has been linked with vascular risk factors and stroke. The authors examined the relationship between retinal microvascular abnormalities and depression symptoms in an elderly population.

METHODS: The Cardiovascular Health Study is a population-based study conducted in four U.S. communities initiated in 1989-1990. A total of 2,420 persons aged 65 years and older were included in the current analyses. During the 1997-1998 examination, retinal photographs were performed and assessed for retinal microvascular abnormalities (retinopathy, focal arteriolar narrowing, arteriovenous nicking, generalized retinal arteriolar narrowing, and generalized retinal venular dilation) according to standardized methods. Depression symptoms were assessed by a modified version of the Centers for Epidemiologic Studies Depression (CES-D) scale annually from 1989 through 1997-1998 and was defined as a CES-D score of >9.

RESULTS: Participants with retinal microvascular abnormalities were not more likely to have depression symptoms, with adjusted odds ratio (OR) (95\% confidence intervals) of 1.08 (0.71-1.65) for retinopathy, OR 1.09 (0.71-1.68) for focal arteriolar narrowing, OR 0.85 (0.52-1.40) for arteriovenous nicking, OR 0.97 (0.70-1.34) for generalized arteriolar narrowing, and OR 0.79 (0.56-1.12) for generalized venular dilation. Retinal microvascular abnormalities were not related to depression symptoms in multinomial logistic regression comparing the three top quartiles of the depression CES-D scores with the lowest quartile.

CONCLUSIONS: Our study did not find an association between retinal microvascular abnormalities and depression symptoms in older people.

}, keywords = {Aged, Aged, 80 and over, Body Mass Index, Cardiovascular Diseases, Cohort Studies, Comorbidity, Cross-Sectional Studies, Depression, Female, Fluorescein Angiography, Humans, Male, Microcirculation, Personality Inventory, Retinal Artery Occlusion, Retinal Diseases, Retinal Vein Occlusion, Risk Factors, Statistics as Topic, United States}, issn = {1064-7481}, doi = {10.1097/01.JGP.0000247161.98311.0f}, author = {Sun, Cong and Tikellis, Gabriella and Klein, Ronald and Steffens, David C and Larsen, Emily K Marino and Siscovick, David S and Klein, Barbara E K and Wong, Tien Y} } @article {965, title = {Retinal microvascular signs, cognitive function, and dementia in older persons: the Cardiovascular Health Study.}, journal = {Stroke}, volume = {38}, year = {2007}, month = {2007 Jul}, pages = {2041-7}, abstract = {

BACKGROUND AND PURPOSE: Cerebral microvascular disease may be a risk factor for the development of dementia in elderly persons. We describe the association of retinal microvascular signs with cognitive function and dementia among older individuals.

METHODS: In the population-based Cardiovascular Health Study, 2211 persons aged 69 to 97 years at recruitment had retinal photography. Photographs were evaluated for retinopathy (eg, microaneurysms, retinal hemorrhages), focal arteriolar narrowing, arteriovenous nicking, and retinal arteriolar and venular caliber. Cognitive status was determined from the Digit-Symbol Substitution Test and Modified Mini-Mental State Examination. Participants were also further evaluated for the presence of dementia with detailed neuropsychological testing. Persons with a prior stroke or taking antipsychotic or antidepressant medications were excluded.

RESULTS: After adjusting for age, gender, race, field center, education level, internal carotid intima-media thickness, body mass index, hypertension, diabetes, and cigarette smoking status, persons with retinopathy had lower mean Digit-Symbol Substitution Test scores but not Modified Mini-Mental State Examination than those without retinopathy (39 versus 41, P=0.002). In hypertensive persons, retinopathy (multivariable-adjusted OR, 2.10; 95\% CI, 1.04 to 4.24) and focal arteriolar narrowing (OR, 3.02; 95\% CI, 1.51 to 6.02) were associated with dementia. These associations were not present in individuals without hypertension.

CONCLUSIONS: In older persons, our study shows a modest cross-sectional association between retinopathy signs with poorer cognitive function and, in persons with hypertension, with dementia. These data support a possible role of cerebral microvascular disease in the pathogenesis of impaired cognitive function and dementia in older hypertensive persons.

}, keywords = {Aged, Aged, 80 and over, Cardiovascular Diseases, Cognition, Cross-Sectional Studies, Dementia, Female, Humans, Longitudinal Studies, Male, Microcirculation, Neuropsychological Tests, Retinal Vessels, Risk Factors}, issn = {1524-4628}, doi = {10.1161/STROKEAHA.107.483586}, author = {Baker, Michelle L and Marino Larsen, Emily K and Kuller, Lewis H and Klein, Ronald and Klein, Barbara E K and Siscovick, David S and Bernick, Charles and Manolio, Teri A and Wong, Tien Yin} } @article {1129, title = {Meta-analysis: retinal vessel caliber and risk for coronary heart disease.}, journal = {Ann Intern Med}, volume = {151}, year = {2009}, month = {2009 Sep 15}, pages = {404-13}, abstract = {

BACKGROUND: Retinal vessel caliber may be a novel marker of coronary heart disease (CHD) risk. However, the sex-specific effect, magnitude of association, and effect independent of traditional CHD disease risk factors remain unclear.

PURPOSE: To determine the association between retinal vessel caliber and risk for CHD.

DATA SOURCES: Relevant studies in any language identified through MEDLINE (1950 to June 2009) and EMBASE (1950 to June 2009) databases.

STUDY SELECTION: Studies were included if they examined a general population, measured retinal vessel caliber from retinal photographs, and documented CHD risk factors and incident CHD events.

DATA EXTRACTION: 6 population-based prospective cohort studies provided data for individual participant meta-analysis.

DATA SYNTHESIS: Proportional hazards models, adjusted for traditional CHD risk factors, were constructed for retinal vessel caliber and incident CHD in women and men. Among 22,159 participants who were free of CHD and followed for 5 to 14 years, 2219 (10.0\%) incident CHD events occurred. Retinal vessel caliber changes (wider venules and narrower arterioles) were each associated with an increased risk for CHD in women (pooled multivariable-adjusted hazard ratios, 1.16 [95\% CI, 1.06 to 1.26] per 20-microm increase in venular caliber and 1.17 [CI, 1.07 to 1.28] per 20-microm decrease in arteriolar caliber) but not in men (1.02 [CI, 0.94 to 1.10] per 20-microm increase in venular caliber and 1.02 [CI, 0.95 to 1.10] per 20-microm decrease in arteriolar caliber). Women without hypertension or diabetes had higher hazard ratios.

LIMITATION: Error in the measurement of retinal vessel caliber and Framingham variables was not taken into account.

CONCLUSION: Retinal vessel caliber changes were independently associated with an increased risk for CHD events in women.

}, keywords = {Adult, Aged, Arterioles, Biomarkers, Coronary Disease, Female, Humans, Male, Middle Aged, Proportional Hazards Models, Retinal Vessels, Risk Factors, Sex Factors, Venules}, issn = {1539-3704}, author = {McGeechan, Kevin and Liew, Gerald and Macaskill, Petra and Irwig, Les and Klein, Ronald and Klein, Barbara E K and Wang, Jie Jin and Mitchell, Paul and Vingerling, Johannes R and Dejong, Paulus T V M and Witteman, Jacqueline C M and Breteler, Monique M B and Shaw, Jonathan and Zimmet, Paul and Wong, Tien Y} } @article {1243, title = {Four novel Loci (19q13, 6q24, 12q24, and 5q14) influence the microcirculation in vivo.}, journal = {PLoS Genet}, volume = {6}, year = {2010}, month = {2010 Oct 28}, pages = {e1001184}, abstract = {

There is increasing evidence that the microcirculation plays an important role in the pathogenesis of cardiovascular diseases. Changes in retinal vascular caliber reflect early microvascular disease and predict incident cardiovascular events. We performed a genome-wide association study to identify genetic variants associated with retinal vascular caliber. We analyzed data from four population-based discovery cohorts with 15,358 unrelated Caucasian individuals, who are members of the Cohort for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium, and replicated findings in four independent Caucasian cohorts (n  =  6,652). All participants had retinal photography and retinal arteriolar and venular caliber measured from computer software. In the discovery cohorts, 179 single nucleotide polymorphisms (SNP) spread across five loci were significantly associated (p<5.0{\texttimes}10(-8)) with retinal venular caliber, but none showed association with arteriolar caliber. Collectively, these five loci explain 1.0\%-3.2\% of the variation in retinal venular caliber. Four out of these five loci were confirmed in independent replication samples. In the combined analyses, the top SNPs at each locus were: rs2287921 (19q13; p  =  1.61{\texttimes}10(-25), within the RASIP1 locus), rs225717 (6q24; p = 1.25{\texttimes}10(-16), adjacent to the VTA1 and NMBR loci), rs10774625 (12q24; p  =  2.15{\texttimes}10(-13), in the region of ATXN2,SH2B3 and PTPN11 loci), and rs17421627 (5q14; p = 7.32{\texttimes}10(-16), adjacent to the MEF2C locus). In two independent samples, locus 12q24 was also associated with coronary heart disease and hypertension. Our population-based genome-wide association study demonstrates four novel loci associated with retinal venular caliber, an endophenotype of the microcirculation associated with clinical cardiovascular disease. These data provide further insights into the contribution and biological mechanisms of microcirculatory changes that underlie cardiovascular disease.

}, keywords = {Adolescent, Adult, Aged, Aged, 80 and over, Cardiovascular Diseases, Child, Child, Preschool, Chromosomes, Human, Pair 12, Chromosomes, Human, Pair 19, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Cohort Studies, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Humans, Male, Meta-Analysis as Topic, Microcirculation, Middle Aged, Polymorphism, Single Nucleotide, Retinal Vessels, Young Adult}, issn = {1553-7404}, doi = {10.1371/journal.pgen.1001184}, author = {Ikram, M Kamran and Sim, Xueling and Xueling, Sim and Jensen, Richard A and Cotch, Mary Frances and Hewitt, Alex W and Ikram, M Arfan and Wang, Jie Jin and Klein, Ronald and Klein, Barbara E K and Breteler, Monique M B and Cheung, Ning and Liew, Gerald and Mitchell, Paul and Uitterlinden, Andr{\'e} G and Rivadeneira, Fernando and Hofman, Albert and de Jong, Paulus T V M and van Duijn, Cornelia M and Kao, Linda and Cheng, Ching-Yu and Smith, Albert Vernon and Glazer, Nicole L and Lumley, Thomas and McKnight, Barbara and Psaty, Bruce M and Jonasson, Fridbert and Eiriksdottir, Gudny and Aspelund, Thor and Harris, Tamara B and Launer, Lenore J and Taylor, Kent D and Li, Xiaohui and Iyengar, Sudha K and Xi, Quansheng and Sivakumaran, Theru A and Mackey, David A and Macgregor, Stuart and Martin, Nicholas G and Young, Terri L and Bis, Josh C and Wiggins, Kerri L and Heckbert, Susan R and Hammond, Christopher J and Andrew, Toby and Fahy, Samantha and Attia, John and Holliday, Elizabeth G and Scott, Rodney J and Islam, F M Amirul and Rotter, Jerome I and McAuley, Annie K and Boerwinkle, Eric and Tai, E Shyong and Gudnason, Vilmundur and Siscovick, David S and Vingerling, Johannes R and Wong, Tien Y} } @article {6027, title = {Genetic loci for retinal arteriolar microcirculation.}, journal = {PLoS One}, volume = {8}, year = {2013}, month = {2013}, pages = {e65804}, abstract = {

Narrow arterioles in the retina have been shown to predict hypertension as well as other vascular diseases, likely through an increase in the peripheral resistance of the microcirculatory flow. In this study, we performed a genome-wide association study in 18,722 unrelated individuals of European ancestry from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium and the Blue Mountain Eye Study, to identify genetic determinants associated with variations in retinal arteriolar caliber. Retinal vascular calibers were measured on digitized retinal photographs using a standardized protocol. One variant (rs2194025 on chromosome 5q14 near the myocyte enhancer factor 2C MEF2C gene) was associated with retinal arteriolar caliber in the meta-analysis of the discovery cohorts at genome-wide significance of P-value <5{\texttimes}10(-8). This variant was replicated in an additional 3,939 individuals of European ancestry from the Australian Twins Study and Multi-Ethnic Study of Atherosclerosis (rs2194025, P-value = 2.11{\texttimes}10(-12) in combined meta-analysis of discovery and replication cohorts). In independent studies of modest sample sizes, no significant association was found between this variant and clinical outcomes including coronary artery disease, stroke, myocardial infarction or hypertension. In conclusion, we found one novel loci which underlie genetic variation in microvasculature which may be relevant to vascular disease. The relevance of these findings to clinical outcomes remains to be determined.

}, keywords = {Aged, Aged, 80 and over, Arterioles, Chromosomes, Human, Pair 5, European Continental Ancestry Group, Female, Genetic Loci, Genome-Wide Association Study, Genotype, Humans, Male, MEF2 Transcription Factors, Microcirculation, Middle Aged, Models, Genetic, Retinal Vessels}, issn = {1932-6203}, doi = {10.1371/journal.pone.0065804}, author = {Sim, Xueling and Jensen, Richard A and Ikram, M Kamran and Cotch, Mary Frances and Li, Xiaohui and Macgregor, Stuart and Xie, Jing and Smith, Albert Vernon and Boerwinkle, Eric and Mitchell, Paul and Klein, Ronald and Klein, Barbara E K and Glazer, Nicole L and Lumley, Thomas and McKnight, Barbara and Psaty, Bruce M and de Jong, Paulus T V M and Hofman, Albert and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and van Duijn, Cornelia M and Aspelund, Thor and Eiriksdottir, Gudny and Harris, Tamara B and Jonasson, Fridbert and Launer, Lenore J and Attia, John and Baird, Paul N and Harrap, Stephen and Holliday, Elizabeth G and Inouye, Michael and Rochtchina, Elena and Scott, Rodney J and Viswanathan, Ananth and Li, Guo and Smith, Nicholas L and Wiggins, Kerri L and Kuo, Jane Z and Taylor, Kent D and Hewitt, Alex W and Martin, Nicholas G and Montgomery, Grant W and Sun, Cong and Young, Terri L and Mackey, David A and van Zuydam, Natalie R and Doney, Alex S F and Palmer, Colin N A and Morris, Andrew D and Rotter, Jerome I and Tai, E Shyong and Gudnason, Vilmundur and Vingerling, Johannes R and Siscovick, David S and Wang, Jie Jin and Wong, Tien Y} } @article {6072, title = {Genome-wide association study of retinopathy in individuals without diabetes.}, journal = {PLoS One}, volume = {8}, year = {2013}, month = {2013}, pages = {e54232}, abstract = {

BACKGROUND: Mild retinopathy (microaneurysms or dot-blot hemorrhages) is observed in persons without diabetes or hypertension and may reflect microvascular disease in other organs. We conducted a genome-wide association study (GWAS) of mild retinopathy in persons without diabetes.

METHODS: A working group agreed on phenotype harmonization, covariate selection and analytic plans for within-cohort GWAS. An inverse-variance weighted fixed effects meta-analysis was performed with GWAS results from six cohorts of 19,411 Caucasians. The primary analysis included individuals without diabetes and secondary analyses were stratified by hypertension status. We also singled out the results from single nucleotide polymorphisms (SNPs) previously shown to be associated with diabetes and hypertension, the two most common causes of retinopathy.

RESULTS: No SNPs reached genome-wide significance in the primary analysis or the secondary analysis of participants with hypertension. SNP, rs12155400, in the histone deacetylase 9 gene (HDAC9) on chromosome 7, was associated with retinopathy in analysis of participants without hypertension, -1.3{\textpm}0.23 (beta {\textpm} standard error), p = 6.6{\texttimes}10(-9). Evidence suggests this was a false positive finding. The minor allele frequency was low (\~{}2\%), the quality of the imputation was moderate (r(2) \~{}0.7), and no other common variants in the HDAC9 gene were associated with the outcome. SNPs found to be associated with diabetes and hypertension in other GWAS were not associated with retinopathy in persons without diabetes or in subgroups with or without hypertension.

CONCLUSIONS: This GWAS of retinopathy in individuals without diabetes showed little evidence of genetic associations. Further studies are needed to identify genes associated with these signs in order to help unravel novel pathways and determinants of microvascular diseases.

}, keywords = {Aged, Aged, 80 and over, Female, Genome-Wide Association Study, Genotype, Histone Deacetylases, Humans, Hypertension, Male, Polymorphism, Single Nucleotide, Repressor Proteins, Retinal Diseases}, issn = {1932-6203}, doi = {10.1371/journal.pone.0054232}, author = {Jensen, Richard A and Sim, Xueling and Li, Xiaohui and Cotch, Mary Frances and Ikram, M Kamran and Holliday, Elizabeth G and Eiriksdottir, Gudny and Harris, Tamara B and Jonasson, Fridbert and Klein, Barbara E K and Launer, Lenore J and Smith, Albert Vernon and Boerwinkle, Eric and Cheung, Ning and Hewitt, Alex W and Liew, Gerald and Mitchell, Paul and Wang, Jie Jin and Attia, John and Scott, Rodney and Glazer, Nicole L and Lumley, Thomas and McKnight, Barbara and Psaty, Bruce M and Taylor, Kent and Hofman, Albert and de Jong, Paulus T V M and Rivadeneira, Fernando and Uitterlinden, Andr{\'e} G and Tay, Wan-Ting and Teo, Yik Ying and Seielstad, Mark and Liu, Jianjun and Cheng, Ching-Yu and Saw, Seang-Mei and Aung, Tin and Ganesh, Santhi K and O{\textquoteright}Donnell, Christopher J and Nalls, Mike A and Wiggins, Kerri L and Kuo, Jane Z and van Duijn, Cornelia M and Gudnason, Vilmundur and Klein, Ronald and Siscovick, David S and Rotter, Jerome I and Tai, E Shong and Vingerling, Johannes and Wong, Tien Y} } @article {7019, title = {Genetic determinants of age-related macular degeneration in diverse populations from the PAGE study.}, journal = {Invest Ophthalmol Vis Sci}, volume = {55}, year = {2014}, month = {2014 Sep 9}, pages = {6839-50}, abstract = {

PURPOSE: Substantial progress has been made in identifying susceptibility variants for AMD in European populations; however, few studies have been conducted to understand the role these variants play in AMD risk in diverse populations. The present study aims to examine AMD risk across diverse populations in known and suspected AMD complement factor and lipid-related loci.

METHODS: Targeted genotyping was performed across study sites for AMD and lipid trait-associated single nucleotide polymorphism (SNPs). Genetic association tests were performed at individual sites and then meta-analyzed using logistic regression assuming an additive genetic model stratified by self-described race/ethnicity. Participants included cases with early or late AMD and controls with no signs of AMD as determined by fundus photography. Populations included in this study were European Americans, African Americans, Mexican Americans, and Singaporeans from the Population Architecture using Genomics and Epidemiology (PAGE) study.

RESULTS: Index variants of AMD, rs1061170 (CFH) and rs10490924 (ARMS2), were associated with AMD at P=3.05{\texttimes}10(-8) and P=6.36{\texttimes}10(-6), respectively, in European Americans. In general, none of the major AMD index variants generalized to our non-European populations with the exception of rs10490924 in Mexican Americans at an uncorrected P value<0.05. Four lipid-associated SNPS (LPL rs328, TRIB1 rs6987702, CETP rs1800775, and KCTD10/MVK rs2338104) were associated with AMD in African Americans and Mexican Americans (P<0.05), but these associations did not survive strict corrections for multiple testing.

CONCLUSIONS: While most associations did not generalize in the non-European populations, variants within lipid-related genes were found to be associated with AMD. This study highlights the need for larger well-powered studies in non-European populations.

}, keywords = {Adult, Aged, Aged, 80 and over, Complement Factor H, DNA, Ethnic Groups, Female, Gene Frequency, Genetic Predisposition to Disease, Genotype, Humans, Macular Degeneration, Male, Middle Aged, Phenotype, Polymorphism, Single Nucleotide, Prevalence, Prospective Studies, Proteins, Risk Factors, United States}, issn = {1552-5783}, doi = {10.1167/iovs.14-14246}, author = {Restrepo, Nicole A and Spencer, Kylee L and Goodloe, Robert and Garrett, Tiana A and Heiss, Gerardo and B{\r u}zkov{\'a}, Petra and Jorgensen, Neal and Jensen, Richard A and Matise, Tara C and Hindorff, Lucia A and Klein, Barbara E K and Klein, Ronald and Wong, Tien Y and Cheng, Ching-Yu and Cornes, Belinda K and Tai, E-Shyong and Ritchie, Marylyn D and Haines, Jonathan L and Crawford, Dana C} } @article {7590, title = {Genetically Determined Plasma Lipid Levels and Risk of Diabetic Retinopathy: A Mendelian Randomization Study.}, journal = {Diabetes}, volume = {66}, year = {2017}, month = {2017 12}, pages = {3130-3141}, abstract = {

Results from observational studies examining dyslipidemia as a risk factor for diabetic retinopathy (DR) have been inconsistent. We evaluated the causal relationship between plasma lipids and DR using a Mendelian randomization approach. We pooled genome-wide association studies summary statistics from 18 studies for two DR phenotypes: any DR (N = 2,969 case and 4,096 control subjects) and severe DR (N = 1,277 case and 3,980 control subjects). Previously identified lipid-associated single nucleotide polymorphisms served as instrumental variables. Meta-analysis to combine the Mendelian randomization estimates from different cohorts was conducted. There was no statistically significant change in odds ratios of having any DR or severe DR for any of the lipid fractions in the primary analysis that used single nucleotide polymorphisms that did not have a pleiotropic effect on another lipid fraction. Similarly, there was no significant association in the Caucasian and Chinese subgroup analyses. This study did not show evidence of a causal role of the four lipid fractions on DR. However, the study had limited power to detect odds ratios less than 1.23 per SD in genetically induced increase in plasma lipid levels, thus we cannot exclude that causal relationships with more modest effect sizes exist.

}, keywords = {Aged, Diabetic Retinopathy, Female, Genome-Wide Association Study, Humans, Lipids, Male, Mendelian Randomization Analysis, Middle Aged, Polymorphism, Single Nucleotide, Risk}, issn = {1939-327X}, doi = {10.2337/db17-0398}, author = {Sobrin, Lucia and Chong, Yong He and Fan, Qiao and Gan, Alfred and Stanwyck, Lynn K and Kaidonis, Georgia and Craig, Jamie E and Kim, Jihye and Liao, Wen-Ling and Huang, Yu-Chuen and Lee, Wen-Jane and Hung, Yi-Jen and Guo, Xiuqing and Hai, Yang and Ipp, Eli and Pollack, Samuela and Hancock, Heather and Price, Alkes and Penman, Alan and Mitchell, Paul and Liew, Gerald and Smith, Albert V and Gudnason, Vilmundur and Tan, Gavin and Klein, Barbara E K and Kuo, Jane and Li, Xiaohui and Christiansen, Mark W and Psaty, Bruce M and Sandow, Kevin and Jensen, Richard A and Klein, Ronald and Cotch, Mary Frances and Wang, Jie Jin and Jia, Yucheng and Chen, Ching J and Chen, Yii-Der Ida and Rotter, Jerome I and Tsai, Fuu-Jen and Hanis, Craig L and Burdon, Kathryn P and Wong, Tien Yin and Cheng, Ching-Yu} }