TY - JOUR
T1 - Parental genetically predicted liability for coronary heart disease and risk of adverse pregnancy outcomes: a cohort study
AU - Hernáez Camba, Alvaro
AU - Skåra, Karoline H.
AU - Page, Christian M.
AU - Mitter, Vera R.
AU - Hernández Hernández, Marta
AU - Magnus, Per
AU - Njølstad, Pål R.
AU - Andreassen, Ole A.
AU - Corfield, Elizabeth C.
AU - Havdahl, Alexandra
AU - Næss, Øyvind
AU - Brumpton, Ben
AU - Åsvold, Bjørn Olav
AU - Lawlor, Deborah A.
AU - Magnus, Maria C.
N1 - © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder.
PY - 2024/1/25
Y1 - 2024/1/25
N2 - Background: Adverse pregnancy outcomes (APO) may unmask or exacerbate a woman’s underlying risk for coronary heart disease (CHD). We estimated associations of maternal and paternal genetically predicted liability for CHD with lifelong risk of APOs. We hypothesized that associations would be found for women, but not their male partners (negative controls). Methods: We studied up to 83,969 women (and up to 55,568 male partners) from the Norwegian Mother, Father and Child Cohort Study or the Trøndelag Health Study with genotyping data and lifetime history of any APO in their pregnancies (1967–2019) in the Medical Birth Registry of Norway (miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, small for gestational age, large for gestational age, and spontaneous preterm birth). Maternal and paternal genetic risk scores (GRS) for CHD were generated using 148 gene variants (p-value < 5 × 10
−8, not in linkage disequilibrium). Associations between GRS for CHD and each APO were determined using logistic regression, adjusting for genomic principal components, in each cohort separately, and combined using fixed effects meta-analysis. Results: One standard deviation higher GRS for CHD in women was related to increased risk of any hypertensive disorders of pregnancy (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05–1.10), pre-eclampsia (OR 1.08, 95% CI 1.05–1.11), and small for gestational age (OR 1.04, 95% CI 1.01–1.06). Imprecise associations with lower odds of large for gestational age (OR 0.98, 95% CI 0.96–1.00) and higher odds of stillbirth (OR 1.04, 95% CI 0.98–1.11) were suggested. These findings remained consistent after adjusting for number of total pregnancies and the male partners’ GRS and restricting analyses to stable couples. Associations for other APOs were close to the null. There was weak evidence of an association of paternal genetically predicted liability for CHD with spontaneous preterm birth in female partners (OR 1.02, 95% CI 0.99–1.05), but not with other APOs. Conclusions: Hypertensive disorders of pregnancy, small for gestational age, and stillbirth may unmask women with a genetically predicted propensity for CHD. The association of paternal genetically predicted CHD risk with spontaneous preterm birth in female partners needs further exploration.
AB - Background: Adverse pregnancy outcomes (APO) may unmask or exacerbate a woman’s underlying risk for coronary heart disease (CHD). We estimated associations of maternal and paternal genetically predicted liability for CHD with lifelong risk of APOs. We hypothesized that associations would be found for women, but not their male partners (negative controls). Methods: We studied up to 83,969 women (and up to 55,568 male partners) from the Norwegian Mother, Father and Child Cohort Study or the Trøndelag Health Study with genotyping data and lifetime history of any APO in their pregnancies (1967–2019) in the Medical Birth Registry of Norway (miscarriage, stillbirth, hypertensive disorders of pregnancy, gestational diabetes, small for gestational age, large for gestational age, and spontaneous preterm birth). Maternal and paternal genetic risk scores (GRS) for CHD were generated using 148 gene variants (p-value < 5 × 10
−8, not in linkage disequilibrium). Associations between GRS for CHD and each APO were determined using logistic regression, adjusting for genomic principal components, in each cohort separately, and combined using fixed effects meta-analysis. Results: One standard deviation higher GRS for CHD in women was related to increased risk of any hypertensive disorders of pregnancy (odds ratio [OR] 1.08, 95% confidence interval [CI] 1.05–1.10), pre-eclampsia (OR 1.08, 95% CI 1.05–1.11), and small for gestational age (OR 1.04, 95% CI 1.01–1.06). Imprecise associations with lower odds of large for gestational age (OR 0.98, 95% CI 0.96–1.00) and higher odds of stillbirth (OR 1.04, 95% CI 0.98–1.11) were suggested. These findings remained consistent after adjusting for number of total pregnancies and the male partners’ GRS and restricting analyses to stable couples. Associations for other APOs were close to the null. There was weak evidence of an association of paternal genetically predicted liability for CHD with spontaneous preterm birth in female partners (OR 1.02, 95% CI 0.99–1.05), but not with other APOs. Conclusions: Hypertensive disorders of pregnancy, small for gestational age, and stillbirth may unmask women with a genetically predicted propensity for CHD. The association of paternal genetically predicted CHD risk with spontaneous preterm birth in female partners needs further exploration.
KW - Adverse pregnancy outcomes
KW - Coronary heart disease
KW - HUNT
KW - MoBa
KW - Parental genetic liability to CHD
UR - http://www.scopus.com/inward/record.url?scp=85183018001&partnerID=8YFLogxK
UR - https://www.webofscience.com/wos/alldb/full-record/WOS:001151393000002
U2 - 10.1186/s12916-023-03223-9
DO - 10.1186/s12916-023-03223-9
M3 - Article
SN - 1741-7015
VL - 22
JO - BMC Medicine
JF - BMC Medicine
IS - art.35
M1 - 35
ER -