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Genomic study of maternal lipid traits in early pregnancy concurs with four known adult lipid loci

  • Marion Ouidir
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
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  • Suvo Chatterjee
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
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  • Jing Wu
    Affiliations
    Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
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  • Fasil Tekola-Ayele
    Correspondence
    Correspondence: Fasil Tekola-Ayele, PhD, Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, 6710B Rockledge Drive, Room 3204, Bethesda, MD 20892-7004
    Affiliations
    Epidemiology Branch, Division of Population Health Research, Division of Intramural Research, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, MD, USA
    Search for articles by this author
Published:November 16, 2022DOI:https://doi.org/10.1016/j.jacl.2022.10.013

      Highlights

      • This first trans-ancestry GWAS of lipids in pregnant women identified 4 known loci.
      • Loci in CELSR2 and APOE were associated with levels of total cholesterol and LDL.
      • Loci in CETP and ABCA1 approached the genome-wide signification with HDL levels.
      • Local replication analysis underlined the need for studies in diverse populations.
      • Colocalization analysis identified CELSR2 as a candidate causal gene.

      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.

      Keywords

      Abbreviations:

      BF (Bayes Factor), eQTL (expression quantitative trait loci), GWAS (Genome-wide association studies), HDL (high-density lipoprotein cholesterol), LD (linkage disequilibrium), LDL (low-density lipoprotein cholesterol), meQTL (methylation quantitative loci), PCs (Principal components), SNPs (single nucleotide polymorphisms), s.d. (standard deviation)
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