A 32 kb Critical Region Excluding Y402H in CFH Mediates Risk for Age-Related Macular Degeneration

Sivakumaran, Theru A.; Igo, Robert P.; Kidd, Jeffrey M.; Itsara, Andy; Kopplin, Laura J.; Chen, Wei; Hagstrom, Stephanie A.; Peachey, Neal S.; Francis, Peter J.; Klein, Michael L.; Chew, Emily Y.; Ramprasad, Vedam Lakshmi; Tay, Wan Ting; Mitchell, Paul; Seielstad, Mark; Stambolian, Dwight; Edwards, Albert O.; Lee, Kristine E.; Leontiev, Dmitry V.; Jun, Gyungah; Wang, Yan; Tian, Liang; Qiu, Feiyou; Henning, Alice K.; LaFramboise, Thomas; Sen, Parveen; Manoharan, Aarthi; George, Ronnie; Raman, Rajiv; Das, Manmath Kumar; Vijaya, Lingam; Kumaramanickavel, Govindasamy; Wong, Tien Yin; Swaroop, Anand; Abecasis, Gonçalo R.; Klein, Ronald; Klein, Barbara E.K.; Nickerson, Deborah A.; Eichler, Evan E.; Iyengar, Sudha K.

doi:10.1371/journal.pone.0025598

Cited by 45 publications

(55 citation statements)

References 46 publications

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“…Certain haplotypes may in fact be protective against AMD, and it would be of interest to investigate whether any haplotypes are associated with reticular pseudodrusen. 50 …”

Section: Discussionmentioning

confidence: 99%

Risk Factors Associated With Reticular Pseudodrusen Versus Large Soft Drusen

Boddu

Lee

Marsiglia

et al. 2014

American Journal of Ophthalmology

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“…Certain haplotypes may in fact be protective against AMD, and it would be of interest to investigate whether any haplotypes are associated with reticular pseudodrusen. 50 …”

Section: Discussionmentioning

confidence: 99%

Risk Factors Associated With Reticular Pseudodrusen Versus Large Soft Drusen

Boddu

Lee

Marsiglia

et al. 2014

American Journal of Ophthalmology

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“…The variant Y402H was genotyped using a Taqman assay in 3015 samples in the BDES, which is described elsewhere. 24;25 This variant was also imputed in 2940 samples based on 70 common SNPs (minor allele frequency >0.05), which were genotyped using Illumina array, in the CFH locus using the MACH program version 1.0. 26 A concordance rate of 99.8% was observed among 1476 samples for which both genotyped and imputed data were available.…”

Section: Methodsmentioning

confidence: 99%

Cigarette Smoking and the Natural History of Age-Related Macular Degeneration

Myers¹,

Klein²,

Gangnon³

et al. 2014

Ophthalmology

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Objective To examine the association of current cigarette smoking and pack-years smoked to 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. Design A longitudinal population-based study of AMD in a representative American community. Examinations were performed every 5 years over a 20-year period. Participants 4439 participants in the population-based Beaver Dam Eye Study. Methods AMD 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 to the incidence and progression of AMD over the entire age range. Main Outcome Measures Incidence and progression of AMD over a 20-year period and interactions between current smoking and pack-years smoked with CFH and ARMS2 genotype. Results 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. Conclusions 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.

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“…23,24 This variant was also imputed in 2940 samples based on 70 common SNPs (minor allele frequency > 0.05), which were genotyped using a commercial array (Illumina, Inc.) in the CFH locus using haplotyper software (MACH 1.0; University of Michigan, Ann Arbor, MI, USA). 25 A concordance rate of 99.8% was observed among 1476 samples for which both genotyped and imputed data were available.…”

Section: Genetic Measurementsmentioning

confidence: 99%