Shared Genetic Links Between Birth Weight and Developmental-Behavioral Disorders

Abstract

While observational studies have linked birth weight to developmental-behavioral disorders, establishing genetic correlations and causal relationships remains challenging due to potential confounding factors. In this study, we assessed genetic correlations between birth weight and developmental-behavioral disorders using linkage disequilibrium score regression (LDSC), identified pleiotropic loci and genes through Pleiotropy Analysis under Composite Null Hypothesis (PLACO), and investigated causal relationships via Mendelian randomization (MR) analysis. The results revealed significant negative genetic correlations between ADHD and birth weight (fetal: rg = −0.087, 95% CI −0.134 to −0.040; maternal: rg = −0.088, 95% CI −0.139 to −0.0337; maternal effect: rg = −0.107, 95% CI −0.183 to −0.030). We identified 41 pleiotropic genes enriched in cardiovascular, brain, and liver tissues, and 122 pleiotropic loci through eQTL integration. However, MR analysis showed no causal associations between birth weight and developmental behavioral disorders. These analyses establish both shared genetic etiology and biological pleiotropy underlying birth weight and developmental-behavioral disorder associations.