Abstract
BACKGROUND: Blood lipids during pregnancy are associated with cardiovascular diseases and adverse pregnancy outcomes. Genome-wide association studies (GWAS) in predominantly male European ancestry populations have identified genetic loci associated with blood lipid levels. However, the genetic architecture of blood lipids in pregnant women remains poorly understood. OBJECTIVE: Our goal was to identify genetic loci associated with blood lipid levels among pregnant women from diverse ancestry groups and to evaluate whether previously known lipid loci in predominantly European adults are transferable to pregnant women. METHODS: The trans-ancestry GWAS were conducted on serum levels of total cholesterol, high-density lipoprotein cholesterol (HDL), low-density lipoprotein cholesterol (LDL) and triglycerides during first trimester among pregnant women from four population groups (608 European-, 623 African-, 552 Hispanic- and 235 East Asian-Americans) recruited in the NICHD Fetal Growth Studies cohort. The four GWAS summary statistics were combined using trans-ancestry meta-analysis approaches that account for genetic heterogeneity among populations. RESULTS: Loci in CELSR2 and APOE were genome-wide significantly associated (p-value < 5×10(-8)) with total cholesterol and LDL levels. Loci near CETP and ABCA1 approached genome-wide significant association with HDL (p-value = 2.97×10(-7) and 9.71×10(-8), respectively). Less than 20% of previously known adult lipid loci were transferable to pregnant women. CONCLUSION: This trans-ancestry GWAS meta-analysis in pregnant women identified associations that concur with four known adult lipid loci. Limited replication of known lipid-loci from predominantly European study populations to pregnant women underlines the need for genomic studies of lipids in ancestrally diverse pregnant women. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT00912132.