ObjectiveNeonatal lupus erythematosus (NLE) is a passively acquired autoimmune disease in infants born to anti-Ro and/or anti-La autoantibody-positive mothers. Genetics may affect NLE risk. We analyzed the genetics of infants and anti-Ro antibody-positive mothers, with NLE and NLE-specific manifestations.MethodsInfants and mothers from a tertiary care clinic underwent genotyping on the Global Screening Array. We created additive non-HLA and HLA polygenic risk scores (PRS) for systemic lupus erythematosus (SLE), from one of the largest genome-wide association studies. Outcomes were any NLE manifestations, cardiac NLE, and cutaneous NLE. We tested the association between SLE-PRS in the infant, mother, and the PRS difference between the mother and infant with NLE outcomes, in logistic regression and generalized linear mixed models (BonferroniP< 0.02). We also performed HLA-wide analyses for the outcomes (P< 5.00 × 10^–8).ResultsThe study included 332 infants, 270 anti-Ro antibody-positive mothers, and 253 mother-infant pairs. A large proportion of mothers (40.4%) and infants (41.3%) were European, and 50% of infants were female. More than half of the infants had NLE (53%), including 7.2% with cardiac NLE and 11.7% with cutaneous NLE. We did not identify significant associations between infant PRS, maternal PRS, or maternal-infant PRS difference and any NLE outcomes. HLA-wide analyses did not identify NLE risk alleles.ConclusionIn a multiethnic cohort of infants and anti-Ro antibody-positive mothers, we did not identify a significant association between SLE genetics and risk of NLE outcomes.