Genetic influence on scar height and pliability after burn injury in individuals of European ancestry: A prospective cohort study

Hilary J Wallace, Gemma Cadby, Phillip E Melton, Fiona M Wood, Sian Falder, Margaret M Crowe, Lisa J Martin, Karen Marlow, Sarah V Ward, Mark W Fear

Research output: Contribution to journalArticle

Abstract

After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings.

Original languageEnglish
Pages (from-to)567-578
Number of pages12
JournalBurns
Volume45
Issue number3
Early online date27 Dec 2018
DOIs
Publication statusPublished - May 2019

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Pliability
Cicatrix
Cohort Studies
Prospective Studies
Wounds and Injuries
Genes
Biological Phenomena
Single Nucleotide Polymorphism
Exome
Comb and Wattles
Body Surface Area
Genetic Models
Cell Adhesion
Nervous System
Fibrosis
Software
DNA

Cite this

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title = "Genetic influence on scar height and pliability after burn injury in individuals of European ancestry: A prospective cohort study",
abstract = "After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium{\circledR} HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and {\%} total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings.",
author = "Wallace, {Hilary J} and Gemma Cadby and Melton, {Phillip E} and Wood, {Fiona M} and Sian Falder and Crowe, {Margaret M} and Martin, {Lisa J} and Karen Marlow and Ward, {Sarah V} and Fear, {Mark W}",
year = "2019",
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language = "English",
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Genetic influence on scar height and pliability after burn injury in individuals of European ancestry : A prospective cohort study. / Wallace, Hilary J; Cadby, Gemma; Melton, Phillip E; Wood, Fiona M; Falder, Sian; Crowe, Margaret M; Martin, Lisa J; Marlow, Karen; Ward, Sarah V; Fear, Mark W.

In: Burns, Vol. 45, No. 3, 05.2019, p. 567-578.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Genetic influence on scar height and pliability after burn injury in individuals of European ancestry

T2 - A prospective cohort study

AU - Wallace, Hilary J

AU - Cadby, Gemma

AU - Melton, Phillip E

AU - Wood, Fiona M

AU - Falder, Sian

AU - Crowe, Margaret M

AU - Martin, Lisa J

AU - Marlow, Karen

AU - Ward, Sarah V

AU - Fear, Mark W

PY - 2019/5

Y1 - 2019/5

N2 - After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings.

AB - After similar extent of injury there is considerable variability in scarring between individuals, in part due to genetic factors. This study aimed to identify genetic variants associated with scar height and pliability after burn injury. An exome-wide array association study and gene pathway analysis were performed on a prospective cohort of 665 patients treated for burn injury. Outcomes were scar height (SH) and scar pliability (SP) sub-scores of the modified Vancouver Scar Scale (mVSS). DNA was genotyped using the Infinium® HumanCoreExome-24 BeadChip. Associations between genetic variants (single nucleotide polymorphisms) and SH and SP were estimated using an additive genetic model adjusting for age, sex, number of surgical procedures and % total body surface area of burn in subjects of European ancestry. No individual genetic variants achieved the cut-off threshold of significance. Gene regions were analysed for spatially correlated single nucleotide polymorphisms and significant regions identified using comb-p software. This gene list was subject to gene pathway analysis to find which biological process terms were over-represented. Using this approach biological processes related to the nervous system and cell adhesion were the predominant gene pathways associated with both SH and SP. This study suggests genes associated with innervation may be important in scar fibrosis. Further studies using similar and larger datasets will be essential to validate these findings.

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