Tsegaselassie Workalemahu1,2, Daniel A Enquobahrie1,3, Bizu Gelaye4, Mahlet G Tadesse5, Sixto E Sanchez6,7, Fasil Tekola-Ayele2, Anjum Hajat1, Timothy A Thornton8, Cande V Ananth9,10,11,12, Michelle A Williams4. 1. Department of Epidemiology, School of Public Health, University of Washington, Seattle, WA, USA. 2. Division of Maternal-Fetal Medicine, Department of Obstetrics and Gynecology, University of Utah, Salt Lake City, UT, USA. 3. Center for Perinatal Studies, Swedish Medical Center, Seattle, WA, USA. 4. Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, MA, USA. 5. Department of Mathematics and Statistics, Georgetown University, Washington, DC, USA. 6. Facultad de Medicina Humana, Universidad de San Martín de Porres, Lima, Peru. 7. Asociación Civil PROESA, Lima, Peru. 8. Department of Biostatistics, University of Washington, Seattle, WA, USA. 9. Division of Epidemiology and Biostatistics, Department of Obstetrics, Gynecology and Reproductive Sciences, Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA. 10. Department of Biostatistics and Epidemiology, Rutgers School of Public Health, Piscataway, NJ, USA. 11. Cardiovascular Institute of New Jersey (CVI-NJ), Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA. 12. Environmental and Occupational Health Sciences Institute (EOHSI), Rutgers Robert Wood Johnson Medical School, New Brunswick, NJ, USA.
Abstract
RESULTS: Abruption cases were more likely to experience preeclampsia, have shorter gestational age, and deliver infants with lower birthweight compared with controls. Models with MFGI effects provided improved fit than models with only maternal and fetal genotype main effects for SNP rs12530904 (p-value = 1.2e-04) in calcium/calmodulin-dependent protein kinase [CaM kinase] II beta (CAMK2B), and, SNP rs73136795 (p-value = 1.9e-04) in peroxisome proliferator-activated receptor-gamma (PPARG), both MB genes. We identified 320 SNPs in 45 maternally-imprinted genes (including potassium voltage-gated channel subfamily Q member 1 [KCNQ1], neurotrimin [NTM], and, ATPase phospholipid transporting 10 A [ATP10A]) associated with abruption. Top hits included rs2012323 (p-value = 1.6E-16) and rs12221520 (p-value1.3e-13) in KCNQ1, rs8036892 (p-value = 9.3E-17) and rs188497582 in ATP10A, rs12589854 (p-value = 2.9E-11) and rs80203467 (p-value = 4.6e-11) in maternally expressed 8, small nucleolar RNA host (MEG8), and rs138281088 in solute carrier family 22 member 2 (SLC22A2) (p-value = 6.8e-9). CONCLUSIONS: We identified novel PA-related maternal-fetal MB gene interactions and imprinting effects that highlight the role of the fetus in PA risk development. Findings can inform mechanistic investigations to understand the pathogenesis of PA.
RESULTS: Abruption cases were more likely to experience preeclampsia, have shorter gestational age, and deliver infants with lower birthweight compared with controls. Models with MFGI effects provided improved fit than models with only maternal and fetal genotype main effects for SNP rs12530904 (p-value = 1.2e-04) in calcium/calmodulin-dependent protein kinase [CaM kinase] II beta (CAMK2B), and, SNP rs73136795 (p-value = 1.9e-04) in peroxisome proliferator-activated receptor-gamma (PPARG), both MB genes. We identified 320 SNPs in 45 maternally-imprinted genes (including potassium voltage-gated channel subfamily Q member 1 [KCNQ1], neurotrimin [NTM], and, ATPase phospholipid transporting 10 A [ATP10A]) associated with abruption. Top hits included rs2012323 (p-value = 1.6E-16) and rs12221520 (p-value1.3e-13) in KCNQ1, rs8036892 (p-value = 9.3E-17) and rs188497582 in ATP10A, rs12589854 (p-value = 2.9E-11) and rs80203467 (p-value = 4.6e-11) in maternally expressed 8, small nucleolar RNA host (MEG8), and rs138281088 in solute carrier family 22 member 2 (SLC22A2) (p-value = 6.8e-9). CONCLUSIONS: We identified novel PA-related maternal-fetal MB gene interactions and imprinting effects that highlight the role of the fetus in PA risk development. Findings can inform mechanistic investigations to understand the pathogenesis of PA.
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