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Genome-wide association studies in Samoans give insight into the genetic architecture of fasting serum lipid levels

Journal of Human Genetics volume 66, pages 111–121 (2021)Cite this article

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Abstract

The current understanding of the genetic architecture of lipids has largely come from genome-wide association studies (GWAS). To date, few GWAS have examined the genetic architecture of lipids in Polynesians, and none have in Samoans, whose unique population history, including many population bottlenecks, may provide insight into the biological foundations of variation in lipid levels. Here we performed a GWAS of four fasting serum lipid levels: total cholesterol (TC), high-density lipoprotein (HDL), low-density lipoprotein (LDL), and triglycerides (TG) in a sample of 2849 Samoans, with validation genotyping for associations in a replication cohort comprising 1798 Samoans and American Samoans. We identified multiple genome-wide significant associations (P < 5 × 10−8) previously seen in other populations—APOA1 with TG, CETP with HDL, and APOE with TC and LDL—and several suggestive associations (P < 1 × 10−5), including an association of variants downstream of MGAT1 and RAB21 with HDL. However, we observed different association signals for variants near APOE than what has been previously reported in non-Polynesian populations. The association with several known lipid loci combined with the newly identified associations with variants near MGAT1 and RAB21 suggest that while some of the genetic architecture of lipids is shared between Samoans and other populations, part of the genetic architecture may be Polynesian-specific.

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Data availability

The discovery cohort data are available from dbGaP (accession number: phs000914.v1.p1). The data from the replication cohort (recruited in 1990–1995 and 2002–2003) are not available as participants were not consented for data sharing.

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Acknowledgements

We would like to thank the Samoan participants of the study, local village authorities, and the many Samoan and other field workers over the years. We acknowledge the Samoan Ministry of Health, the Samoa Bureau of Statistics, and the American Samoan Department of Health for their support of this research. We give particular thanks to two research assistants, Melania Selu and Vaimoana Lupematasila, who contributed to the 2010 recruitment and continue to assist us in our work in Samoa. This work was funded by the National Institute of Health grants R01HL093093 (STM), R01HL133040 (RLM), R01AG09375 (STM), R01HL52611 (MI Kamboh), R01DK59642 (STM), and R01DK55406 (RD). Genotyping was performed in the Core Genotyping Laboratory at the University of Cincinnati, funded by National Institutes of Health grant P30ES006096 (SM Ho).

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Author notes

  1. These authors jointly supervised this work: Daniel E. Weeks, Ranjan Deka, Stephen T. McGarvey, Ryan L. Minster

Authors and Affiliations

  1. Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Jenna C. Carlson, Daniel E. Weeks & Ryan L. Minster

  2. Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA

    Jenna C. Carlson & Daniel E. Weeks

  3. Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA

    Nicola L. Hawley

  4. Department of Environmental Health, College of Medicine, University of Cincinnati, Cincinnati, OH, USA

    Guangyun Sun, Hong Cheng & Ranjan Deka

  5. Ministry of Health, Government of Samoa, Apia, Samoa

    Take Naseri

  6. Lutia i Puava ae Mapu i Fagalele, Apia, Samoa

    Muagututi‘a Sefuiva Reupena

  7. Department of Public Health, Government of American Samoa, Pago Pago, AS, USA

    John Tuitele

  8. International Health Institute and Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA

    Stephen T. McGarvey

  9. Department of Anthropology, Brown University, Providence, RI, USA

    Stephen T. McGarvey

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Correspondence to Ryan L. Minster.

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Joint Senior Authors: Daniel E. Weeks, Ranjan Deka, Stephen T. McGarvey and Ryan L. Minster

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Carlson, J.C., Weeks, D.E., Hawley, N.L. et al. Genome-wide association studies in Samoans give insight into the genetic architecture of fasting serum lipid levels. J Hum Genet 66, 111–121 (2021). https://doi.org/10.1038/s10038-020-0816-9

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