Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects.
Conotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses u...
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doaj-3151f7ca816e4d1980ccf5483f189e162021-03-03T21:28:49ZengPublic Library of Science (PLoS)PLoS ONE1932-62032019-01-01147e021992610.1371/journal.pone.0219926Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects.Anshuman SewdaA J AgopianElizabeth GoldmuntzHakon HakonarsonBernice E MorrowDeanne TaylorLaura E MitchellPediatric Cardiac Genomics ConsortiumConotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses using microarray-genotyped and imputed common and rare variants data from two large studies of CTDs in the United States. We performed two case-parent trio analyses (N = 640 and 317 trios), using an extension of the family-based multi-marker association test, and two case-control analyses (N = 482 and 406 patients and comparable numbers of controls), using a sequence kernel association test. We also undertook two meta-analyses to combine the results from the analyses that used the same approach (i.e. family-based or case-control). To our knowledge, these analyses are the first reported gene-based, genome-wide association studies of CTDs. Based on our findings, we propose eight CTD candidate genes (ARF5, EIF4E, KPNA1, MAP4K3, MBNL1, NCAPG, NDFUS1 and PSMG3). Four of these genes (ARF5, KPNA1, NDUFS1 and PSMG3) have not been previously associated with normal or abnormal heart development. In addition, our analyses provide additional evidence that genes involved in chromatin-modification and in ribonucleic acid splicing are associated with congenital heart defects.https://doi.org/10.1371/journal.pone.0219926 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Anshuman Sewda A J Agopian Elizabeth Goldmuntz Hakon Hakonarson Bernice E Morrow Deanne Taylor Laura E Mitchell Pediatric Cardiac Genomics Consortium |
spellingShingle |
Anshuman Sewda A J Agopian Elizabeth Goldmuntz Hakon Hakonarson Bernice E Morrow Deanne Taylor Laura E Mitchell Pediatric Cardiac Genomics Consortium Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. PLoS ONE |
author_facet |
Anshuman Sewda A J Agopian Elizabeth Goldmuntz Hakon Hakonarson Bernice E Morrow Deanne Taylor Laura E Mitchell Pediatric Cardiac Genomics Consortium |
author_sort |
Anshuman Sewda |
title |
Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. |
title_short |
Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. |
title_full |
Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. |
title_fullStr |
Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. |
title_full_unstemmed |
Gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. |
title_sort |
gene-based genome-wide association studies and meta-analyses of conotruncal heart defects. |
publisher |
Public Library of Science (PLoS) |
series |
PLoS ONE |
issn |
1932-6203 |
publishDate |
2019-01-01 |
description |
Conotruncal heart defects (CTDs) are among the most common and severe groups of congenital heart defects. Despite evidence of an inherited genetic contribution to CTDs, little is known about the specific genes that contribute to the development of CTDs. We performed gene-based genome-wide analyses using microarray-genotyped and imputed common and rare variants data from two large studies of CTDs in the United States. We performed two case-parent trio analyses (N = 640 and 317 trios), using an extension of the family-based multi-marker association test, and two case-control analyses (N = 482 and 406 patients and comparable numbers of controls), using a sequence kernel association test. We also undertook two meta-analyses to combine the results from the analyses that used the same approach (i.e. family-based or case-control). To our knowledge, these analyses are the first reported gene-based, genome-wide association studies of CTDs. Based on our findings, we propose eight CTD candidate genes (ARF5, EIF4E, KPNA1, MAP4K3, MBNL1, NCAPG, NDFUS1 and PSMG3). Four of these genes (ARF5, KPNA1, NDUFS1 and PSMG3) have not been previously associated with normal or abnormal heart development. In addition, our analyses provide additional evidence that genes involved in chromatin-modification and in ribonucleic acid splicing are associated with congenital heart defects. |
url |
https://doi.org/10.1371/journal.pone.0219926 |
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