Exome-Wide Rare Variant Analyses in Sudden Infant Death Syndrome.
J Pediatr
; 203: 423-428.e11, 2018 12.
Article
en En
| MEDLINE
| ID: mdl-30268395
ABSTRACT
OBJECTIVE:
To determine whether a monogenic basis explains sudden infant death syndrome (SIDS) using an exome-wide focus. STUDYDESIGN:
A cohort of 427 unrelated cases of SIDS (257 male; average age = 2.7 ± 1.9 months) underwent whole-exome sequencing. Exome-wide rare variant analyses were carried out with 278 SIDS cases of European ancestry (173 male; average age = 2.7 ± 1.98 months) and 973 ethnic-matched controls based on 6 genetic models. Ingenuity Pathway Analysis also was performed. The cohort was collected in collaboration with coroners, medical examiners, and pathologists by St George's University of London, United Kingdom, and Mayo Clinic, Rochester, Minnesota. Whole-exome sequencing was performed at the Genomic Laboratory, Kings College London, United Kingdom, or Mayo Clinic's Medical Genome Facility, Rochester, Minnesota.RESULTS:
Although no exome-wide significant (P < 2.5 × 10-6) difference in burden of ultra-rare variants was detected for any gene, 405 genes had a greater prevalence (P < .05) of ultra-rare nonsynonymous variants among cases with 17 genes at P < .005. Some of these potentially overrepresented genes may represent biologically plausible novel candidate genes for a monogenic basis for a portion of patients with SIDS. The top canonical pathway identified was glucocorticoid biosynthesis (P = .01).CONCLUSIONS:
The lack of exome-wide significant genetic associations indicates an extreme heterogeneity of etiologies underlying SIDS. Our approach to understanding the genetic mechanisms of SIDS has far reaching implications for the SIDS research community as a whole and may catalyze new evidence-based SIDS research across multiple disciplines. Perturbations in glucocorticoid biosynthesis may represent a novel SIDS-associated biological pathway for future SIDS investigative research.Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Muerte Súbita del Lactante
/
Predisposición Genética a la Enfermedad
/
Exoma
Tipo de estudio:
Observational_studies
/
Risk_factors_studies
Límite:
Child
/
Child, preschool
/
Female
/
Humans
/
Infant
/
Male
País/Región como asunto:
America do norte
/
Europa
Idioma:
En
Revista:
J Pediatr
Año:
2018
Tipo del documento:
Article
País de afiliación:
Mongolia