Key result
BTNL9 stop-gain variant linked to ~1.6 mg/dL lower HDL-C and higher TG in Polynesian populations.
Why the study?
Limited genetic studies have focused on Polynesian populations despite their unique history and high prevalence of dyslipidemia, which may reveal novel lipid level variation.
Is a stop-gain variant in BTNL9 associated with altered HDL-C and triglyceride levels in Polynesian populations?
Meta-Analysis (n=2,851)
Yes
Is a stop-gain variant in BTNL9 associated with altered HDL-C and triglyceride levels in Polynesian populations?
A Polynesian-specific stop-gain variant in BTNL9 is significantly associated with an atherogenic lipid profile, highlighting a novel genetic contributor to dyslipidemia.
May refine ancestry-specific lipid risk assessment in Polynesians; extends lipid genetic architecture beyond European-ancestry populations.
Current understanding of lipid genetics has come mainly from studies in European-ancestry populations; limited effort has focused on Polynesian populations, whose unique population history and high prevalence of dyslipidemia may provide insight into the biological foundations of variation in lipid levels. Here, we performed an association study to fine map a suggestive association on 5q35 with high-density lipoprotein cholesterol (HDL-C) seen in Micronesian and Polynesian populations. Fine-mapping analyses in a cohort of 2,851 Samoan adults highlighted an association between a stop-gain variant (rs200884524; c.652C>T, p.R218∗; posterior probability = 0.9987) in BTNL9 and both lower HDL-C and greater triglycerides (TGs). Meta-analysis across this and several other cohorts of Polynesian ancestry from Samoa, American Samoa, and Aotearoa New Zealand confirmed the presence of this association (βHDL-C = −1.60 mg/dL, pHDL-C = 7.63 × 10−10; βTG = 12.00 mg/dL, pTG = 3.82 × 10−7). While this variant appears to be Polynesian specific, there is also evidence of association from other multiancestry analyses in this region. This work provides evidence of a previously unexplored contributor to the genetic architecture of lipid levels and underscores the importance of genetic analyses in understudied populations.
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Carlson et al. (2022) conducted a meta-analysis in Dyslipidemia (n=2,851). BTNL9 stop-gain variant (rs200884524) vs. Absence of variant was evaluated on High-density lipoprotein cholesterol (HDL-C) levels (β -1.60 mg/dL, p=7.63 × 10−10). A stop-gain variant in BTNL9 (rs200884524) was associated with lower HDL-C (β = -1.60 mg/dL, p = 7.63 × 10−10) and higher triglycerides in populations of Polynesian ancestry.
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