Noncardiac genetic predisposition in sudden infant death syndrome
Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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.
I: Genetics in Medicine, Bind 21, Nr. 3, 2019, s. 641–649.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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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