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Haplotypes spanning the complement factor H gene are protective against age-related macular degeneration.

Publication ,  Journal Article
Spencer, KL; Hauser, MA; Olson, LM; Schnetz-Boutaud, N; Scott, WK; Schmidt, S; Gallins, P; Agarwal, A; Postel, EA; Pericak-Vance, MA; Haines, JL
Published in: Invest Ophthalmol Vis Sci
September 2007

PURPOSE: Age-related macular degeneration (AMD) is a devastating disorder that adversely affects the quality of life of nearly 2 million Americans who have advanced forms of the disease. Besides the well-known risk imparted by carrying the Y402H variant in the complement factor H (CFH) gene on chromosome 1, recent evidence of the existence of protective haplotypes spanning CFH has been reported. METHODS: The haplo.stats program was used to test for association of the protective haplotypes after adjusting for age in the dataset of 584 sporadic cases and 248 control samples. Logistic regression modeling and likelihood ratio tests were used to investigate an interaction between a particular haplotype and smoking status. The HBAT option of FBAT was used to confirm the associations in an independent dataset of 201 families. RESULTS: Two protective (P) haplotypes in a family-based dataset (P1 = CAATTTAG, P = 0.021; and P2 = CGGCTTAG, P = 0.018) were identified for the first time. Age-adjusted score statistics provided support for these protective haplotypes in the case-control dataset (P1 frequency in cases approximately 13%, in controls approximately 20%, P = 0.001; P2 frequency in cases approximately 5%, in controls approximately 8%, P = 0.077). There was also tentative evidence of an interaction between one of the protective haplotypes and cigarette smoking (P = 0.04 likelihood ratio test for P2-smoking interaction). CONCLUSIONS: Replication of the association between the protective haplotypes and decreased AMD susceptibility provides increased evidence that these associations have biological meaning. The suggestion of a haplotype-smoking interaction adds to the growing body of evidence that smoking is an important environmental covariate in AMD that should be considered in genetic studies. Identification of the protective variant(s) carried within these haplotypes is critical for understanding the etiology of AMD.

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Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

September 2007

Volume

48

Issue

9

Start / End Page

4277 / 4283

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry
  • Male
  • Macular Degeneration
  • Likelihood Functions
  • Humans
  • Haplotypes
  • Genetic Variation
 

Citation

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Spencer, K. L., Hauser, M. A., Olson, L. M., Schnetz-Boutaud, N., Scott, W. K., Schmidt, S., … Haines, J. L. (2007). Haplotypes spanning the complement factor H gene are protective against age-related macular degeneration. Invest Ophthalmol Vis Sci, 48(9), 4277–4283. https://doi.org/10.1167/iovs.06-1427
Spencer, Kylee L., Michael A. Hauser, Lana M. Olson, Nathalie Schnetz-Boutaud, William K. Scott, Silke Schmidt, Paul Gallins, et al. “Haplotypes spanning the complement factor H gene are protective against age-related macular degeneration.Invest Ophthalmol Vis Sci 48, no. 9 (September 2007): 4277–83. https://doi.org/10.1167/iovs.06-1427.
Spencer KL, Hauser MA, Olson LM, Schnetz-Boutaud N, Scott WK, Schmidt S, et al. Haplotypes spanning the complement factor H gene are protective against age-related macular degeneration. Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4277–83.
Spencer, Kylee L., et al. “Haplotypes spanning the complement factor H gene are protective against age-related macular degeneration.Invest Ophthalmol Vis Sci, vol. 48, no. 9, Sept. 2007, pp. 4277–83. Pubmed, doi:10.1167/iovs.06-1427.
Spencer KL, Hauser MA, Olson LM, Schnetz-Boutaud N, Scott WK, Schmidt S, Gallins P, Agarwal A, Postel EA, Pericak-Vance MA, Haines JL. Haplotypes spanning the complement factor H gene are protective against age-related macular degeneration. Invest Ophthalmol Vis Sci. 2007 Sep;48(9):4277–4283.

Published In

Invest Ophthalmol Vis Sci

DOI

ISSN

0146-0404

Publication Date

September 2007

Volume

48

Issue

9

Start / End Page

4277 / 4283

Location

United States

Related Subject Headings

  • Smoking
  • Risk Factors
  • Polymorphism, Single Nucleotide
  • Ophthalmology & Optometry
  • Male
  • Macular Degeneration
  • Likelihood Functions
  • Humans
  • Haplotypes
  • Genetic Variation