title: Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.
abstract: Age-related macular degeneration (AMD) is the leading cause of blindness in the elderly in the developed world. We conducted a genome-wide association study in a series of families enriched for AMD and completed a meta-analysis of this new data with results from reanalysis of an existing study of a late-stage case-control cohort. We tested the top findings for replication in 1896 cases and 1866 controls and identified two novel genetic protective factors for AMD. In addition to the complement factor H (CFH) (P=2.3 × 10⁻⁶⁴) and age-related maculopathy susceptibility 2 (ARMS2) (P=1.2 × 10⁻⁶⁰) loci, we observed a protective effect at rs429608, an intronic SNP in SKIV2L (P=5.3 × 10⁻¹⁵), a gene near the complement component 2 (C2)/complement factor B (BF) locus, that indicates the protective effect may be mediated by variants other than the C2/BF variants previously studied. Haplotype analysis at this locus identified three protective haplotypes defined by the rs429608 protective allele. We also identified a new potentially protective effect at rs2679798 in MYRIP (P=2.9 × 10⁻⁴), a gene involved in retinal pigment epithelium melanosome trafficking. Interestingly, MYRIP was initially identified in the family-based scan and was confirmed in the case-control set. From these efforts, we report the identification of two novel protective factors for AMD and confirm the previously known associations at CFH, ARMS2 and C3.
authors.affiliation: Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.
authors.forename: L J
authors.initials: LJ
authors.lastname: Kopplin
authors.forename: R P
authors.initials: RP
authors.lastname: Igo
authors.forename: Y
authors.initials: Y
authors.lastname: Wang
authors.forename: T A
authors.initials: TA
authors.lastname: Sivakumaran
authors.forename: S A
authors.initials: SA
authors.lastname: Hagstrom
authors.forename: N S
authors.initials: NS
authors.lastname: Peachey
authors.forename: P J
authors.initials: PJ
authors.lastname: Francis
authors.forename: M L
authors.initials: ML
authors.lastname: Klein
authors.forename: J P
authors.initials: JP
authors.lastname: SanGiovanni
authors.forename: E Y
authors.initials: EY
authors.lastname: Chew
authors.forename: G J T
authors.initials: GJ
authors.lastname: Pauer
authors.forename: G M
authors.initials: GM
authors.lastname: Sturgill
authors.forename: T
authors.initials: T
authors.lastname: Joshi
authors.forename: L
authors.initials: L
authors.lastname: Tian
authors.forename: Q
authors.initials: Q
authors.lastname: Xi
authors.forename: A K
authors.initials: AK
authors.lastname: Henning
authors.forename: K E
authors.initials: KE
authors.lastname: Lee
authors.forename: R
authors.initials: R
authors.lastname: Klein
authors.forename: B E K
authors.initials: BE
authors.lastname: Klein
authors.forename: S K
authors.initials: SK
authors.lastname: Iyengar
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D017242:Complement Factor H / Q000235:genetics*; D004265:DNA Helicases / Q000235:genetics*; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008268:Macular Degeneration / Q000235:genetics*; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D033921:Vesicular Transport Proteins / Q000235:genetics*
chemical_list: C514392:ARMS2 protein, human; C501262:MYRIP protein, human; D011506:Proteins; D033921:Vesicular Transport Proteins; D017242:Complement Factor H; D004265:DNA Helicases; C114718:SKIV2L protein, human