Low-frequency and rare variants may contribute to elucidate the genetics of major depressive disorder

Major depressive disorder (MDD) is a common but serious psychiatric disorder with significant levels of morbidity and mortality. Recent genome-wide association studies (GWAS) on common variants increase our understanding of MDD; however, the underlying genetic basis remains largely unknown. Many studies have been proposed to explore the genetics of complex diseases from a viewpoint of the "missing heritability" by considering low-frequency and rare variants, copy-number variations, and other types of genetic variants. Here we developed a novel computational and statistical strategy to investigate the "missing heritability" of MDD. We applied Hamming distance on common, low-frequency, and rare single-nucleotide polymorphism (SNP) sets to measure genetic distance between two individuals, and then built the multi-dimensional scaling (MDS) pictures. Whole-exome genotyping data from a Los Angeles Mexican-American cohort (203 MDD and 196 controls) and a European-ancestry cohort (473 MDD and 497 controls) were examined using our proposed methodology. MDS plots showed very significant separations between MDD cases and healthy controls for low-frequency SNP set (P value < 2.2e-16) and rare SNP set (P value = 7.681e-12). Our results suggested that low-frequency and rare variants may play more significant roles in the genetics of MDD. © 2018 The Author(s).

• Fecha de publicación: 2018
• Institución: Universidad del Rosario
• Repositorio: Repositorio EdocUR - U. Rosario
• Idioma: eng
• OAI Identifier: oai:repository.urosario.edu.co:10336/20331
• Acceso en línea: https://repository.urosario.edu.co/handle/10336/20331
• Palabra clave: California; Controlled Study; European American; Genetic Analysis; Genetic Variability; Genotype; Hamming Distance; Heritability; Human; Major Clinical Study; Major Depression; Mexican American; Single Nucleotide Polymorphism; Statistical Analysis; Whole Exome Sequencing; Estudio controlado; Americana Europea; Enfermedades; Controlled Study; Article; European American; Hamming Distance; Genotype; Depresión mental; Variación genética
• License: Abierto (Texto Completo)