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

by Jing Chen, Jonas Bacelis, Pol Sole-Navais, Amit Srivastava, Julius Juodakis, Amy Rouse, Mikko Hallman, Kari Teramo, Mads Melbye, Bjarke Feenstra, Rachel M. Freathy, George Davey Smith, Deborah A. Lawlor, Jeffrey C. Murray, Scott M. Williams, Bo Jacobsson, Louis J. Muglia, Ge Zhang BackgroundMany 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 findingsBased 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 effe cts 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). B...
Source: PLoS Medicine - Category: Internal Medicine Authors: Source Type: research