@article{6f70433cd9514ccc94c8950d7f09bb7d,
title = "Noncardiac genetic predisposition in sudden infant death syndrome",
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.",
keywords = "Genetics, exome sequencing, molecular autopsy, sudden infant death syndrome",
author = "Belinda Gray and Tester, {David J.} and Wong, {Leonie Ch} and Pritha Chanana and Amie Jaye and Evans, {Jared M.} and Baruteau, {Alban Elouen} and Margaret Evans and Peter Fleming and Iona Jeffrey and Marta Cohen and Jacob Tfelt-Hansen and Simpson, {Michael A.} and Ackerman, {Michael J.} and Behr, {Elijah R.}",
note = "Funding Information: The authors gratefully acknowledge both the medical examiners and coroners in both the United Kingdom and the United States for referring the sudden death victims to our programs in an effort to find an explanation for the infant{\textquoteright}s sudden death. This work was supported by Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health (R01HD042569 to M.J.A.) and by the British Heart Foundation ([L.W. and E.R.B.] BHF Clinical Research Training Fellowship FS/13/78/30520). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. D.J.T. and M.J.A. are also supported by the Mayo Clinic Windland Smith Rice Comprehensive Sudden Cardiac Death Program. B.G. is supported by a National Health and Medical Research Council (NHMRC) Early Career Fellowship (1122330). L.W. was also supported by additional funds from Biotronik and Cardiac Risk in the Young. E.R.B. is supported by the Higher Education Funding Council for England and receives funds from The Robert Lancaster Memorial Fund sponsored by McColl{\textquoteright}s Retail Group Ltd. The establishment of the Edinburgh SIDS DNA cohort was supported by a grant from Newlife Foundation. Publisher Copyright: {\textcopyright} 2018, American College of Medical Genetics and Genomics.",
year = "2019",
month = mar,
day = "1",
doi = "10.1038/s41436-018-0131-4",
language = "English (US)",
volume = "21",
pages = "641--649",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "Lippincott Williams and Wilkins",
number = "3",
}