HGG Advances (Jul 2023)
A Polynesian-specific missense CETP variant alters the lipid profile
- Jaye Moors,
- Mohanraj Krishnan,
- Nick Sumpter,
- Riku Takei,
- Matt Bixley,
- Murray Cadzow,
- Tanya J. Major,
- Amanda Phipps-Green,
- Ruth Topless,
- Marilyn Merriman,
- Malcolm Rutledge,
- Ben Morgan,
- Jenna C. Carlson,
- Jerry Z. Zhang,
- Emily M. Russell,
- Guangyun Sun,
- Hong Cheng,
- Daniel E. Weeks,
- Take Naseri,
- Muagututi’a Sefuiva Reupena,
- Satupa’itea Viali,
- John Tuitele,
- Nicola L. Hawley,
- Ranjan Deka,
- Stephen T. McGarvey,
- Janak de Zoysa,
- Rinki Murphy,
- Nicola Dalbeth,
- Lisa Stamp,
- Mele Taumoepeau,
- Frances King,
- Phillip Wilcox,
- Nuku Rapana,
- Sally McCormick,
- Ryan L. Minster,
- Tony R. Merriman,
- Megan Leask
Affiliations
- Jaye Moors
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Mohanraj Krishnan
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Nick Sumpter
- Division of Clinical Rheumatology and Immunology, University of Alabama at Birmingham, Birmingham, AL, USA
- Riku Takei
- Division of Clinical Rheumatology and Immunology, University of Alabama at Birmingham, Birmingham, AL, USA
- Matt Bixley
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Murray Cadzow
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Tanya J. Major
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Amanda Phipps-Green
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Ruth Topless
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Marilyn Merriman
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Malcolm Rutledge
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Ben Morgan
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Jenna C. Carlson
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Jerry Z. Zhang
- Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Emily M. Russell
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Guangyun Sun
- Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
- Hong Cheng
- Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
- Daniel E. Weeks
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA; Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Take Naseri
- Ministry of Health, Apia, Samoa; International Health Institute, Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA
- Muagututi’a Sefuiva Reupena
- Lutia i Puava‘ae Mapu i Fagalele, Apia, Samoa
- Satupa’itea Viali
- School of Medicine, National University of Samoa, Apia, Samoa
- John Tuitele
- Department of Public Health, Lyndon B. Johnson Tropical Medical Center, Faga’alu, American Samoa, USA
- Nicola L. Hawley
- Department of Chronic Disease Epidemiology, Yale School of Public Health, New Haven, CT, USA
- Ranjan Deka
- Department of Environmental and Public Health Sciences, College of Medicine, University of Cincinnati, Cincinnati, OH, USA
- Stephen T. McGarvey
- International Health Institute, Department of Epidemiology, School of Public Health, Brown University, Providence, RI, USA
- Janak de Zoysa
- Department of Medicine, University of Auckland, Auckland, New Zealand
- Rinki Murphy
- Department of Medicine, University of Auckland, Auckland, New Zealand
- Nicola Dalbeth
- Department of Medicine, University of Auckland, Auckland, New Zealand
- Lisa Stamp
- Department of Medicine, University of Otago, Christchurch, New Zealand
- Mele Taumoepeau
- Department of Psychology, University of Otago, Dunedin, New Zealand
- Frances King
- Ngāti Porou Hauora, Te Puia Springs, New Zealand
- Phillip Wilcox
- Department of Mathematics and Statistics, University of Otago, Dunedin, New Zealand
- Nuku Rapana
- Pukapukan Community Centre, Māngere, Auckland, New Zealand
- Sally McCormick
- Department of Biochemistry, University of Otago, Dunedin, New Zealand
- Ryan L. Minster
- Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PA, USA
- Tony R. Merriman
- Department of Biochemistry, University of Otago, Dunedin, New Zealand; Division of Clinical Rheumatology and Immunology, University of Alabama at Birmingham, Birmingham, AL, USA; Corresponding author
- Megan Leask
- Department of Biochemistry, University of Otago, Dunedin, New Zealand; Division of Clinical Rheumatology and Immunology, University of Alabama at Birmingham, Birmingham, AL, USA; Corresponding author
- Journal volume & issue
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Vol. 4,
no. 3
p. 100204
Abstract
Summary: Identifying population-specific genetic variants associated with disease and disease-predisposing traits is important to provide insights into the genetic determinants of health and disease between populations, as well as furthering genomic justice. Various common pan-population polymorphisms at CETP associate with serum lipid profiles and cardiovascular disease. Here, sequencing of CETP identified a missense variant rs1597000001 (p.Pro177Leu) specific to Māori and Pacific people that associates with higher HDL-C and lower LDL-C levels. Each copy of the minor allele associated with higher HDL-C by 0.236 mmol/L and lower LDL-C by 0.133 mmol/L. The rs1597000001 effect on HDL-C is comparable with CETP Mendelian loss-of-function mutations that result in CETP deficiency, consistent with our data, which shows that rs1597000001 lowers CETP activity by 27.9%. This study highlights the potential of population-specific genetic analyses for improving equity in genomics and health outcomes for population groups underrepresented in genomic studies.
