1. Dissecting maternal and fetal genetic effects underlying the associations between maternal phenotypes, birth outcomes, and adult phenotypes:a mendelian-randomization and haplotype-based genetic score analysis in 10,734 mother–infant pairs
- Author
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Chen, J. (Jing), Bacelis, J. (Jonas), Sole-Navais, P. (Pol), Srivastava, A. (Amit), Juodakis, J. (Julius), Rouse, A. (Amy), Hallman, M. (Mikko), Teramo, K. (Kari), Melbye, M. (Mads), Feenstra, B. (Bjarke), Freathy, R. M. (Rachel M.), Smith, G. D. (George Davey), Lawlor, D. A. (Deborah A.), Murray, J. C. (Jeffrey C.), Williams, S. M. (Scott M.), Jacobsson, B. (Bo), Muglia, L. J. (Louis J.), Zhang, G. (Ge), Chen, J. (Jing), Bacelis, J. (Jonas), Sole-Navais, P. (Pol), Srivastava, A. (Amit), Juodakis, J. (Julius), Rouse, A. (Amy), Hallman, M. (Mikko), Teramo, K. (Kari), Melbye, M. (Mads), Feenstra, B. (Bjarke), Freathy, R. M. (Rachel M.), Smith, G. D. (George Davey), Lawlor, D. A. (Deborah A.), Murray, J. C. (Jeffrey C.), Williams, S. M. (Scott M.), Jacobsson, B. (Bo), Muglia, L. J. (Louis J.), and Zhang, G. (Ge)
- Abstract
Background/Objectives: Many maternal traits are associated with a neonate’s gestational duration, birth weight, and birth length. These birth outcomes are subsequently associated with late-onset health conditions. The causal mechanisms and the relative contributions of maternal and fetal genetic effects behind these observed associations are unresolved. Methods and findings: Based on 10,734 mother–infant duos of European ancestry from the UK, Northern Europe, Australia, and North America, we constructed haplotype genetic scores using single-nucleotide polymorphisms (SNPs) known to be associated with adult height, body mass index (BMI), blood pressure (BP), fasting plasma glucose (FPG), and type 2 diabetes (T2D). Using these scores as genetic instruments, we estimated the maternal and fetal genetic effects underlying the observed associations between maternal phenotypes and pregnancy outcomes. We also used infant-specific birth weight genetic scores as instrument and examined the effects of fetal growth on pregnancy outcomes, maternal BP, and glucose levels during pregnancy. The maternal nontransmitted haplotype score for height was significantly associated with gestational duration (p = 2.2 × 10⁻⁴). Both maternal and paternal transmitted height haplotype scores were highly significantly associated with birth weight and length (p < 1 × 10⁻¹⁷). The maternal transmitted BMI scores were associated with birth weight with a significant maternal effect (p = 1.6 × 10⁻⁴). Both maternal and paternal transmitted BP scores were negatively associated with birth weight with a significant fetal effect (p = 9.4 × 10⁻³), whereas BP alleles were significantly associated with gestational duration and preterm birth through maternal effects (p = 3.3 × 10⁻² and p = 4.5 × 10⁻³, respectively). The nontransmitted haplotype score for FPG was strongly associated with birth weight (p = 4.7 × 10⁻⁶); however, the glucose-increasing alleles in the fetus were associated with reduced bi
- Published
- 2020