Abstract
Several genome-wide association studies (GWAS) have identified genetic variants associated with birth weight. To date, however, most GWAS of birth weight have focused primarily on European ancestry samples even though prevalence of low birth weight is higher among African-Americans. We conducted admixture mapping using 2918 ancestral informative markers in 2596 participants of the Black Women’s Health Study, with the goal of identifying novel genomic regions where local African ancestry is associated with birth weight. In addition, we performed a replication analysis of 11 previously identified index single nucleotide polymorphisms (SNPs), and fine-mapped those genetic loci to identify better or new genetic variants associated with birth weight in African-Americans. We found that high African ancestry at 12q14 was associated with low birth weight, and we identified multiple independent birth weight-lowering variants in this genomic region. We replicated the association of a previous GWAS SNP in ADRB1 and our fine-mapping efforts suggested the presence of new birth weight-associated variants in ADRB1, HMGA2, and SLC2A4. Further studies are needed to determine whether birth weight-associated loci can in part explain race-associated birth weight disparities.
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Acknowledgements
We thank the BWHS participants for their continuing participation in this research effort. This work was supported by grants R01MD007015 from the National Institute on Minority Health and Health Disparities, R01CA058420 and UM1CA164974 from the National Cancer Institute, and 11SDG7390014 from the American Heart Association. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute on Minority Health and Health Disparities, the National Cancer Institute, the National Institutes of Health, or the American Heart Association.
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Ochs-Balcom, H.M., Shaw, H., Preus, L. et al. Admixture mapping and fine-mapping of birth weight loci in the Black Women’s Health Study. Hum Genet 137, 535–542 (2018). https://doi.org/10.1007/s00439-018-1908-x
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DOI: https://doi.org/10.1007/s00439-018-1908-x