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 stu...
- Autores:
- Tipo de recurso:
- 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
- Rights
- License
- Abierto (Texto Completo)
| Summary: | 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). |
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