A stop-gain variant in BTNL9 is associated with atherogenic lipid profiles

Carlson, Jenna C.; Krishnan, Mohanraj; Rosenthal, Samantha L.; Russell, Emily M.; Zhang, Jerry Z; Hawley, Nicola L.; Moors, Jaye; Cheng, Hong; Dalbeth, Nicola; Zoysa, Janak R de; Watson, Huti; Qasim, Muhammad; Murphy, Rinki; Naseri, Take; Reupena, Muagututi’a Sefuiva; Stamp, Lisa K.; Tuitele, John; Kershaw, Erin E.; Deka, Ranjan; McGarvey, Stephen T.; Merriman, Tony R.; Weeks, Daniel E.; Minster, Ryan L.

doi:10.1016/j.xhgg.2022.100155

Cited by 1 publication

(4 citation statements)

References 63 publications

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“…For rs200884524 the imputation quality is highest (r 2 = 0.89-0.95) for the reference panels that include Samoan haplotypes (Table 2). Additionally, the MAF among the imputed genotypes in the 1,834 non-reference-panel Samoans from protocols #3-9 (0.207-0.222) is much closer to what is expected -targeted genotyping in separate cohorts of similar ancestry yielded a MAF of 0.202-0.233 31 . The TOPMed imputation yielded a much more accurate imputed MAF than 1000G, which may suggest the presence of some Pacific haplotypes at this locus.…”

Section: Population-specific Variation and The Effect Of Phasingmentioning

confidence: 55%

“…We have performed GWAS to dissect the genetic architecture of cardiometabolic disease traits in these cohorts. Through this, we have identified variants of high frequency in Samoa not appearing (at least at high frequency) in other non-Pacific-Islander populations associated with body mass index 30 and lipid traits 31 , which may be at high frequency due to these founding events and bottlenecks. Interestingly, these variants were not present in initial GWAS using genotyping array data only.…”

Section: Introductionmentioning

confidence: 90%

“…For this paper, imputation was performed on chromosomes 5 and 21 for computational efficiency and to examine imputation of a variant on chromosome 5 associated with atherogenic lipid profiles that is enriched in Polynesians (rs200884524, [hg38] chr5:181050285 C>T in BTNL9 31 ). Various imputation protocols (nine in total, described in Table 1; Figure S1) were implemented to assess imputation accuracy compared to extant panels, measure the impact of additional population-specific samples added to the panel, and investigate how the phasing of the reference panel impacts the imputation of population-specific variation.…”

Section: Construction Of the Reference Panelsmentioning

confidence: 99%

mentioning

confidence: 98%

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Improving imputation quality in Samoans through the integration of population-specific sequences into existing reference panels

Carlson,

Krishnan,

Liu

et al. 2023

Preprint

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Genotype imputation is fundamental to association studies, and yet even gold standard panels like TOPMed are limited in the populations for which they yield good imputation. Specifically, Pacific Islanders are poorly represented in extant panels. To address this, we constructed an imputation reference panel using 1,285 Samoan individuals with whole-genome sequencing, combined with 1000 Genomes (1000G) samples, to create a reference panel that better represents Pacific Islander, specifically Samoan, genetic variation. We compared this panel to 1000G and TOPMed panels based on imputed variants using genotyping array data for 1,834 Samoan participants who were not part of the panels. The 1000G + 1285 Samoan panel yielded up to 2.25-2.76 times more well-imputed (r2≥ 0.80) variants than TOPMed and 1000G. There was improved imputation accuracy across the minor allele frequency (MAF) spectrum, although it was more pronounced for variants with 0.01 ≤ MAF ≤ 0.05. Imputation accuracy (r2) was greater for population-specific variants (high fixation index, FST) and those from larger haplotypes (high LD score). The gain in imputation accuracy over TOPMed was largest for small haplotypes (low LD score), reflecting the Samoan panel’s ability to capture population-specific variation not well tagged by other panels. We also augmented the 1000G reference panel with varying numbers of Samoan samples and found that panels with 48 or more Samoans included outperformed TOPMed for all variants with MAF ≥ 0.001. This study identifies variants with improved imputation using population-specific reference panels and provides a framework for constructing other population-specific reference panels.

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Section: Population-specific Variation and The Effect Of Phasingmentioning

confidence: 55%

Section: Introductionmentioning

confidence: 90%

Section: Construction Of the Reference Panelsmentioning

confidence: 99%

mentioning

confidence: 98%

See 2 more Smart Citations

Improving imputation quality in Samoans through the integration of population-specific sequences into existing reference panels

Carlson,

Krishnan,

Liu

et al. 2023

Preprint

Self Cite

View full text Add to dashboard Cite

show abstract

A stop-gain variant in BTNL9 is associated with atherogenic lipid profiles

Cited by 1 publication

References 63 publications

Improving imputation quality in Samoans through the integration of population-specific sequences into existing reference panels

Improving imputation quality in Samoans through the integration of population-specific sequences into existing reference panels

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