Noncardiac genetic predisposition in sudden infant death syndrome

Belinda Gray, David J Tester, Leonie Ch Wong, Pritha Chanana, Amie Jaye, Jared M Evans, Alban-Elouen Baruteau, Margaret Evans, Peter Fleming, Iona Jeffrey, Marta Cohen, Jacob Tfelt-Hansen, Michael A Simpson, Michael J Ackerman, Elijah R Behr

Research output: Contribution to journalArticle (Academic Journal)peer-review

3 Citations (Scopus)
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Abstract

PURPOSE: Sudden infant death syndrome (SIDS) is the commonest cause of sudden death of an infant; however, the genetic basis remains poorly understood. We aimed to identify noncardiac genes underpinning SIDS and determine their prevalence compared with ethnically matched controls.

METHODS: Using exome sequencing we assessed the yield of ultrarare nonsynonymous variants (minor allele frequency [MAF] ≤0.00005, dominant model; MAF ≤0.01, recessive model) in 278 European SIDS cases (62% male; average age =2.7 ± 2 months) versus 973 European controls across 61 noncardiac SIDS-susceptibility genes. The variants were classified according to American College of Medical Genetics and Genomics criteria. Case-control, gene-collapsing analysis was performed in eight candidate biological pathways previously implicated in SIDS pathogenesis.

RESULTS: Overall 43/278 SIDS cases harbored an ultrarare single-nucleotide variant compared with 114/973 controls (15.5 vs. 11.7%, p=0.10). Only 2/61 noncardiac genes were significantly overrepresented in cases compared with controls (ECE1, 3/278 [1%] vs. 1/973 [0.1%] p=0.036; SLC6A4, 2/278 [0.7%] vs. 1/973 [0.1%] p=0.049). There was no difference in yield of pathogenic or likely pathogenic variants between cases and controls (1/278 [0.36%] vs. 4/973 [0.41%]; p=1.0). Gene-collapsing analysis did not identify any specific biological pathways to be significantly associated with SIDS.

CONCLUSIONS: A monogenic basis for SIDS amongst the previously implicated noncardiac genes and their encoded biological pathways is negligible.

Original languageEnglish
JournalGenetics in Medicine
Early online date24 Aug 2018
DOIs
Publication statusE-pub ahead of print - 24 Aug 2018

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