Noncardiac genetic predisposition in sudden infant death syndrome

Research output: Contribution to journal › Journal article › Research › peer-review

Standard

Noncardiac genetic predisposition in sudden infant death syndrome. / Gray, Belinda; Tester, David J.; Wong, Leonie Ch; Chanana, Pritha; Jaye, Amie; Evans, Jared M.; Baruteau, Alban Elouen; Evans, Margaret; Fleming, Peter; Jeffrey, Iona; Cohen, Marta; Tfelt-Hansen, Jacob; Simpson, Michael A.; Ackerman, Michael J.; Behr, Elijah R.

In: Genetics in Medicine, Vol. 21, No. 3, 2019, p. 641–649.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Gray, B, Tester, DJ, Wong, LC, Chanana, P, Jaye, A, Evans, JM, Baruteau, AE, Evans, M, Fleming, P, Jeffrey, I, Cohen, M, Tfelt-Hansen, J, Simpson, MA, Ackerman, MJ & Behr, ER 2019, 'Noncardiac genetic predisposition in sudden infant death syndrome', Genetics in Medicine, vol. 21, no. 3, pp. 641–649. https://doi.org/10.1038/s41436-018-0131-4

APA

Gray, B., Tester, D. J., Wong, L. C., Chanana, P., Jaye, A., Evans, J. M., Baruteau, A. E., Evans, M., Fleming, P., Jeffrey, I., Cohen, M., Tfelt-Hansen, J., Simpson, M. A., Ackerman, M. J., & Behr, E. R. (2019). Noncardiac genetic predisposition in sudden infant death syndrome. Genetics in Medicine, 21(3), 641–649. https://doi.org/10.1038/s41436-018-0131-4

Vancouver

Gray B, Tester DJ, Wong LC, Chanana P, Jaye A, Evans JM et al. Noncardiac genetic predisposition in sudden infant death syndrome. Genetics in Medicine. 2019;21(3):641–649. https://doi.org/10.1038/s41436-018-0131-4

Author

Gray, Belinda ; Tester, David J. ; Wong, Leonie Ch ; Chanana, Pritha ; Jaye, Amie ; Evans, Jared M. ; Baruteau, Alban Elouen ; Evans, Margaret ; Fleming, Peter ; Jeffrey, Iona ; Cohen, Marta ; Tfelt-Hansen, Jacob ; Simpson, Michael A. ; Ackerman, Michael J. ; Behr, Elijah R. / Noncardiac genetic predisposition in sudden infant death syndrome. In: Genetics in Medicine. 2019 ; Vol. 21, No. 3. pp. 641–649.

Bibtex

@article{38dd5370f39846949a6bf906e7d10313,
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 = "exome sequencing, Genetics, 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.}",
year = "2019",
doi = "10.1038/s41436-018-0131-4",
language = "English",
volume = "21",
pages = "641–649",
journal = "Genetics in Medicine",
issn = "1098-3600",
publisher = "nature publishing group",
number = "3",

}

RIS

TY - JOUR

T1 - Noncardiac genetic predisposition in sudden infant death syndrome

AU - Gray, Belinda

AU - Tester, David J.

AU - Wong, Leonie Ch

AU - Chanana, Pritha

AU - Jaye, Amie

AU - Evans, Jared M.

AU - Baruteau, Alban Elouen

AU - Evans, Margaret

AU - Fleming, Peter

AU - Jeffrey, Iona

AU - Cohen, Marta

AU - Tfelt-Hansen, Jacob

AU - Simpson, Michael A.

AU - Ackerman, Michael J.

AU - Behr, Elijah R.

PY - 2019

Y1 - 2019

N2 - 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.

AB - 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.

KW - exome sequencing

KW - Genetics

KW - molecular autopsy

KW - sudden infant death syndrome

U2 - 10.1038/s41436-018-0131-4

DO - 10.1038/s41436-018-0131-4

M3 - Journal article

C2 - 30139991

AN - SCOPUS:85052924773

VL - 21

SP - 641

EP - 649

JO - Genetics in Medicine

JF - Genetics in Medicine

SN - 1098-3600

IS - 3

ER -

ID: 203562135