Genome-wide association identifies SKIV2L and MYRIP as protective factors for age-related macular degeneration.
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.
Kopplin
L J
LJ
Department of Genetics, Case Western Reserve University, Cleveland, OH 44106, USA.
Igo
R P
RP
Wang
Y
Y
Sivakumaran
T A
TA
Hagstrom
S A
SA
Peachey
N S
NS
Francis
P J
PJ
Klein
M L
ML
SanGiovanni
J P
JP
Chew
E Y
EY
Pauer
G J T
GJ
Sturgill
G M
GM
Joshi
T
T
Tian
L
L
Xi
Q
Q
Henning
A K
AK
Lee
K E
KE
Klein
R
R
Klein
B E K
BE
Iyengar
S K
SK
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*
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