Abstract
The genetic mechanisms of childhood development in its many facets remain largely undeciphered. In the population of healthy infants studied in the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) program, we have identified a range of dependencies among the observed phenotypes of fetal and early childhood growth, neurological development, and a number of genetic variants. We have quantified these dependencies using our information theory-based methods. The genetic variants show dependencies with single phenotypes as well as pleiotropic effects on more than one phenotype and thereby point to a large number of brain-specific and brain-expressed gene candidates. These dependencies provide a basis for connecting a range of variants with a spectrum of phenotypes (pleiotropy) as well as with each other. A broad survey of known regulatory expression characteristics, and other function-related information from the literature for these sets of candidate genes allowed us to assemble an integrated body of evidence, including a partial regulatory network, that points towards the biological basis of these general dependencies. Notable among the implicated loci are RAB11FIP4 (next to NF1), MTMR7 and PLD5, all highly expressed in the brain; DNMT1 (DNA methyl transferase), highly expressed in the placenta; and PPP1R12B and DMD (dystrophin), known to be important growth and development genes. While we cannot specify and decipher the mechanisms responsible for the phenotypes in this study, a number of connections for further investigation of fetal and early childhood growth and neurological development are indicated. These results and this approach open the door to new explorations of early human development.
Funder
Bill and Melinda Gates Foundation
Publisher
Public Library of Science (PLoS)
Reference106 articles.
1. Childhood stunting in relation to the pre- and postnatal environment during the first 2 years of life: The MAL-ED longitudinal birth cohort study;MAL-ED Network Investigators;PLoS Med.,2017
2. Gamma power in rural Pakistani children: Links to executive function and verbal ability;AR Tarullo;Dev Cogn Neurosci,2017
3. Insights from the growing up in Singapore towards healthy outcomes (GUSTO) cohort study;SE Soh;Ann Nutr Metab,2014
4. Identification of risk loci with shared effects on five major psychiatric disorders: a genome-wide analysis;Cross-Disorder Group of the Psychiatric Genomics Consortium;Lancet,2013
Cited by
9 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献