Placental expression quantitative trait loci in an East Asian population
Summary: Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We cond...
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| Format: | Article |
| Language: | English |
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Elsevier
2024-04-01
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| Series: | HGG Advances |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2666247724000150 |
| _version_ | 1797303924751859712 |
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| author | Jaeyong Choi Seung Mi Lee Errol R. Norwitz Ji Hoi Kim Young Mi Jung Chan-Wook Park Jong Kwan Jun Dakyung Lee Yongjoon Jin Sookyung Kim Bukyoung Cha Joong Shin Park Jong-Il Kim |
| author_facet | Jaeyong Choi Seung Mi Lee Errol R. Norwitz Ji Hoi Kim Young Mi Jung Chan-Wook Park Jong Kwan Jun Dakyung Lee Yongjoon Jin Sookyung Kim Bukyoung Cha Joong Shin Park Jong-Il Kim |
| author_sort | Jaeyong Choi |
| collection | DOAJ |
| description | Summary: Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We conducted eQTL analysis on placentas collected from an East Asian population in an effort to identify gene regulatory mechanisms in this tissue. Placentas (n = 102) were collected at the time of cesarean delivery. mRNA was extracted, sequenced with NGS, and compared with matched maternal and fetal DNA arrays performed using maternal and neonatal cord blood. Linear regression modeling was performed using tensorQTL. Fine-mapping along with epigenomic annotation was used to select putative functional variants. We identified 2,703 coding genes that contained at least one eQTL with statistical significance (false discovery rate <0.05). After fine-mapping, we found 108 previously unreported eQTL variants with posterior inclusion probability >0.1. Of these, 19% were located in genomic regions with evidence from public placental epigenome suggesting that they may be functionally relevant. For example, variant rs28379289 located in the placenta-specific regulatory region changes the binding affinity of transcription factor leading to higher expression of LGALS3, which is known to affect placental function. This study expands the knowledge base of regulatory elements within the human placenta and identifies 108 previously unreported placenta eQTL signals, which are listed in our publicly available GMI eQTL database. Further studies are needed to identify and characterize genetic regulatory mechanisms that affect placental function in normal pregnancy and placenta-related diseases. |
| first_indexed | 2024-03-07T23:59:42Z |
| format | Article |
| id | doaj.art-5537b659b4d941c7a3aab6ef70d4bb24 |
| institution | Directory Open Access Journal |
| issn | 2666-2477 |
| language | English |
| last_indexed | 2024-03-07T23:59:42Z |
| publishDate | 2024-04-01 |
| publisher | Elsevier |
| record_format | Article |
| series | HGG Advances |
| spelling | doaj.art-5537b659b4d941c7a3aab6ef70d4bb242024-02-18T04:43:38ZengElsevierHGG Advances2666-24772024-04-0152100276Placental expression quantitative trait loci in an East Asian populationJaeyong Choi0Seung Mi Lee1Errol R. Norwitz2Ji Hoi Kim3Young Mi Jung4Chan-Wook Park5Jong Kwan Jun6Dakyung Lee7Yongjoon Jin8Sookyung Kim9Bukyoung Cha10Joong Shin Park11Jong-Il Kim12Department of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, KoreaDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, KoreaTufts University School of Medicine, Boston, MA, USADepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, KoreaDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, KoreaDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, KoreaDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, KoreaDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, KoreaGenomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, KoreaGenomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, KoreaDepartment of Obstetrics and Gynecology, Seoul National University College of Medicine, Seoul, Korea; Corresponding authorDepartment of Biomedical Sciences, Seoul National University College of Medicine, Seoul, Korea; Genomic Medicine Institute, Medical Research Center, Seoul National University, Seoul, Korea; Corresponding authorSummary: Expression quantitative trait loci (eQTL) analysis measures the contribution of genetic variation in gene expression on complex traits. Although this methodology has been used to examine gene regulation in numerous human tissues, eQTL research in solid tissues is relatively lacking. We conducted eQTL analysis on placentas collected from an East Asian population in an effort to identify gene regulatory mechanisms in this tissue. Placentas (n = 102) were collected at the time of cesarean delivery. mRNA was extracted, sequenced with NGS, and compared with matched maternal and fetal DNA arrays performed using maternal and neonatal cord blood. Linear regression modeling was performed using tensorQTL. Fine-mapping along with epigenomic annotation was used to select putative functional variants. We identified 2,703 coding genes that contained at least one eQTL with statistical significance (false discovery rate <0.05). After fine-mapping, we found 108 previously unreported eQTL variants with posterior inclusion probability >0.1. Of these, 19% were located in genomic regions with evidence from public placental epigenome suggesting that they may be functionally relevant. For example, variant rs28379289 located in the placenta-specific regulatory region changes the binding affinity of transcription factor leading to higher expression of LGALS3, which is known to affect placental function. This study expands the knowledge base of regulatory elements within the human placenta and identifies 108 previously unreported placenta eQTL signals, which are listed in our publicly available GMI eQTL database. Further studies are needed to identify and characterize genetic regulatory mechanisms that affect placental function in normal pregnancy and placenta-related diseases.http://www.sciencedirect.com/science/article/pii/S2666247724000150placentaRNA sequencingexpression quantitative trait locus |
| spellingShingle | Jaeyong Choi Seung Mi Lee Errol R. Norwitz Ji Hoi Kim Young Mi Jung Chan-Wook Park Jong Kwan Jun Dakyung Lee Yongjoon Jin Sookyung Kim Bukyoung Cha Joong Shin Park Jong-Il Kim Placental expression quantitative trait loci in an East Asian population HGG Advances placenta RNA sequencing expression quantitative trait locus |
| title | Placental expression quantitative trait loci in an East Asian population |
| title_full | Placental expression quantitative trait loci in an East Asian population |
| title_fullStr | Placental expression quantitative trait loci in an East Asian population |
| title_full_unstemmed | Placental expression quantitative trait loci in an East Asian population |
| title_short | Placental expression quantitative trait loci in an East Asian population |
| title_sort | placental expression quantitative trait loci in an east asian population |
| topic | placenta RNA sequencing expression quantitative trait locus |
| url | http://www.sciencedirect.com/science/article/pii/S2666247724000150 |
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