rs1061147

badMag 6.5

This is a synonymous variant in the CFH gene — it does not change the protein's amino acid sequence.

Key Literature Trait Associations

Age-Related Macular Degeneration

rs1061147 is a synonymous variant (Ala307Ala) in exon 7 of complement factor H (CFH) that is in strong linkage disequilibrium with the Y402H coding variant (rs1061170). The A allele tags the major AMD risk haplotype in CFH, which disrupts complement regulation on Bruch's membrane and promotes chronic inflammation in the macula. In a study of 3,647 individuals across familial, sporadic, and AREDS cohorts, the A allele was associated with an OR of 2.53 for advanced AMD.

Holliday EG et al. “Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.” Plos One 8(1):e53830 (2013)

Allele A

OR 1.40

p 1.5e-31

N 24,542

Meta-analysisLarge GWAS

European; Asian

Francis PJ et al. “Haplotypes in the complement factor H (CFH) gene: associations with drusen and advanced age-related macular degeneration.” Plos One 2(11):e1197 (2007)

Allele A

OR 2.53

p 1.0e-4

Candidate gene study

“Association of complement factor H polymorphisms with exudative age-related macular degeneration”

Allele A

OR 1.68

p 1.0e-3

N 407

Candidate gene study

Chinese

Plasma protein levels (lysosomal alpha-glucosidase)

The rs1061147 A allele is associated with lower circulating lysosomal alpha-glucosidase (GAA) levels in plasma (beta=−0.109 SD, p=4×10⁻¹⁵) in a large proteogenomic study of 10,708 European participants. This cis-pQTL signal is consistent with the CFH locus exerting broad regulatory effects on local gene expression and protein levels beyond complement factor H itself. The clinical significance of this specific protein-level effect is not yet established.

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)

Allele A

OR —

β -0.109 ±0.014

p 4.0e-15

N 10,708

Large GWAS

European

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GWAS Catalog Trait Associations (2)

Genome-wide significant associations (p < 5×10⁻⁸) from the NHGRI-EBI GWAS Catalog.

age-related macular degeneration

Holliday EG et al. “Insights into the genetic architecture of early stage age-related macular degeneration: a genome-wide association study meta-analysis.” Plos One 8(1):e53830 (2013)

Allele A

OR 1.40

p 7.0e-32

N 19,805

Meta-analysisLarge GWAS

multi-ancestry

protein measurement

Pietzner M et al. “Mapping the proteo-genomic convergence of human diseases.” Science (new York, N.y.) 374(6569):eabj1541 (2021)

Allele A

OR 0.11

p 4.0e-15

N 10,708

Large GWAS

European

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ClinVar annotation

Benign★★★☆

9 submitters9 publications

Age related macular degeneration 4; Atypical hemolytic-uremic syndrome; Basal laminar drusen; CFH-Related Dense Deposit Disease / Membranoproliferative Glomerulonephritis Type II; Factor H deficiency (CFHD); Hemolytic uremic syndrome, atypical, susceptibility to, 1

View on ClinVar →

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Research that mentions this SNP (1)

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Ethnic variation in AMD-associated complement factor H polymorphism p.Tyr402His

AssociationN=514Michael A. Grassi et al.(2006)· Human Mutation

This study documents ethnic variation in the CFH p.Tyr402His (rs1061170, c.1204T>C) polymorphism, a known AMD risk factor (OR ~2.5-4.6 in Caucasians). The risk allele C frequency varies widely across populations: Japanese 7%, Hispanic 17%, African American 35%, Caucasian 34%, and Somali 34%. The findings suggest additional genetic or protective factors beyond CFH contribute to the ethnic differences in AMD prevalence.

rs1061147

Key Literature Trait Associations

Age-Related Macular Degeneration

Plasma protein levels (lysosomal alpha-glucosidase)

GWAS Catalog Trait Associations (2)

age-related macular degeneration

protein measurement

ClinVar annotation

Research that mentions this SNP (1)

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