Assessment of CFH and HTRA1 polymorphisms in age-related macular degeneration using classic and machine-learning approaches

• Published in: Ophthalmic genetics Vol. 41; no. 6; pp. 539 - 547
• Main Authors: Martínez-Velasco, Antonieta, Perez-Ortiz, Andric C, Antonio-Aguirre, Bani, Martínez-Villaseñor, Lourdes, Lira-Romero, Esmeralda, Palacio-Pastrana, Claudia, Zenteno, Juan Carlos, Ramirez, Israel, Zepeda-Palacio, Claudia, Mendoza-Velásquez, Cristina, Camacho-Ordóñez, Azyadeh, Ortiz Bibriesca, Daniela Michelle, Estrada-Mena, F Javier
• Format: Journal Article
• Language: English
• Published: England 01.11.2020
• Subjects: Aged; Case-Control Studies; Complement Factor H - genetics; Ethnicity; Female; Genetic Predisposition to Disease; High-Temperature Requirement A Serine Peptidase 1 - genetics; Humans; Machine Learning; Macular Degeneration - genetics; Macular Degeneration - pathology; Male; Phenotype; Polymorphism, Single Nucleotide; machine-learning; Age-related macular degeneration; high-temperature requirement A serine peptidase 1; complement factor H; genetic association study
• ISSN: 1381-6810; 1744-5094
• DOI: 10.1080/13816810.2020.1804945

and are pivotal genes driving increased risk for age-related macular degeneration (AMD) among several populations. Here, we performed a hospital-based case-control study to evaluate the effects of three single nucleotide polymorphisms (SNPs) among Hispanics from Mexico. 122 cases and 249 controls were genotyped using Taqman probes. Experienced ophthalmologists diagnosed AMD following the American Association of Ophthalmology guidelines. We studied (rs1329428, rs203687) and (rs11200638) SNPs thoroughly by logistic regression models (assuming different modes of inheritance) and machine learning-based methods (ML). rs11200638 is the most significant polymorphism associated with AMD in our studied population. In a multivariate regression model adjusted for clinically and statistically meaningful covariates, the A/G and A/A genotypes increased the odds of disease by a factor of 2.32 and 7.81, respectively ( < .05) suggesting a multiplicative effect of the polymorphic A allele. Furthermore, this observation remains statistically meaningful in the allelic, dominant, and recessive models, and ML algorithms. When stratifying by phenotype, this polymorphism was significantly associated with increased odds for geographic atrophy (GA) in a recessive mode of inheritance (12.4, < .05). In sum, this work supports a strong association between genetic variants and AMD in Hispanics from Mexico, especially with GA. Moreover, ML was able to replicate the results of conventional biostatistics methods unbiasedly.