Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth

Johanna M Huusko; Heli Tiensuu; Antti M Haapalainen; Anu Pasanen; Pinja Tissarinen; Minna K Karjalainen; Ge Zhang; Kaare Christensen; Kelli K Ryckman; Bo Jacobsson; Jeffrey C Murray; Stephen F Kingsmore; Mikko Hallman; Louis J Muglia; Mika Rämet

doi:10.1038/s41598-021-96374-9

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Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth

Journal article

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Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth

Johanna M Huusko, Heli Tiensuu, Antti M Haapalainen, Anu Pasanen, Pinja Tissarinen, Minna K Karjalainen, Ge Zhang, Kaare Christensen, Kelli K Ryckman, Bo Jacobsson, …

Scientific reports, Vol.11(1), pp.17115-17115

2021

DOI: 10.1038/s41598-021-96374-9

PMCID: PMC8384995

PMID: 34429451

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Abstract

Heat shock proteins are involved in the response to stress including activation of the immune response. Elevated circulating heat shock proteins are associated with spontaneous preterm birth (SPTB). Intracellular heat shock proteins act as multifunctional molecular chaperones that regulate activity of nuclear hormone receptors. Since SPTB has a significant genetic predisposition, our objective was to identify genetic and transcriptomic evidence of heat shock proteins and nuclear hormone receptors that may affect risk for SPTB. We investigated all 97 genes encoding members of the heat shock protein families and all 49 genes encoding nuclear hormone receptors for their potential role in SPTB susceptibility. We used multiple genetic and genomic datasets including genome-wide association studies (GWASs), whole-exome sequencing (WES), and placental transcriptomics to identify SPTB predisposing factors from the mother, infant, and placenta. There were multiple associations of heat shock protein and nuclear hormone receptor genes with SPTB. Several orthogonal datasets supported roles for SEC63, HSPA1L, SACS, RORA, and AR in susceptibility to SPTB. We propose that suppression of specific heat shock proteins promotes maintenance of pregnancy, whereas activation of specific heat shock protein mediated signaling may disturb maternal-fetal tolerance and promote labor.

Obstetrics, Gynecology and Reproductive Medicine

Reproduktionsmedicin och gynekologi

Details

Title: Subtitle: Integrative genetic, genomic and transcriptomic analysis of heat shock protein and nuclear hormone receptor gene associations with spontaneous preterm birth
Creators: Johanna M Huusko
Heli Tiensuu
Antti M Haapalainen
Anu Pasanen
Pinja Tissarinen
Minna K Karjalainen
Ge Zhang
Kaare Christensen
Kelli K Ryckman
Bo Jacobsson - Institute of Clinical Sciences, Department of Obstetrics and Gynecology
Jeffrey C Murray
Stephen F Kingsmore
Mikko Hallman
Louis J Muglia
Mika Rämet
Resource Type: Journal article
Publication Details: Scientific reports, Vol.11(1), pp.17115-17115
DOI: 10.1038/s41598-021-96374-9
PMID: 34429451
PMCID: PMC8384995
NLM abbreviation: Sci Rep
ISSN: 2045-2322
eISSN: 2045-2322
Grant note: name: NIH Genes, Environment, and Health Initiative, award: U01HG004423, dbGaP accession number phs000103.v1.p1; name: NIH/NIEHS, award: N01-ES-75558; name: NIH/NINDS, award: no. 1 UO1 NS 047537-01 and grant no. 2 UO1 NS 047537-06A1; DOI: 10.13039/501100004012, name: Jane ja Aatos Erkon Säätiö; DOI: 10.13039/501100006306, name: Sigrid Juséliuksen Säätiö; DOI: 10.13039/501100005744, name: Lastentautien Tutkimussäätiö; name: Competitive State Research Financing of the Expert Responsibility Area of Oulu University Hospital
Language: English
Date published: 2021
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984214702702771

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