Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Dai, Juncheng; Huang, Mingtao; Amos, Christopher I.; Hung, Rayjean J.; Tardón, Adonina; Andrew, Angeline S.; Chen, Chu; Christiani, David C.; Albanês, Demetrius; Rennert, Gad; Fan, Jingyi; Goodman, Gary E.; Liu, Geoffrey; Field, John K.; Grankvist, Kjell; Kiemeney, Lambertus A.; Marchand, Loı̈c Le; Schabath, Matthew B.; Johansson, Mattias; Aldrich, Melinda C.; Johansson, Mikael; Caporaso, Neil E.; Lazarus, Philip; Lam, Stephan; Bojesen, Stig E.; Arnold, Susanne M.; Landi, Maria Teresa; Risch, Angela; Wichmann, H‐Erich; Bickeböller, Heike; Brennan, Paul; Shete, Sanjay; Melander, Olle; Brunnström, Hans; Zienolddiny, Shan; Woll, Penella J.; Stevens, Victoria L.; Hu, Zhibin; Shen, Hongbing

doi:10.1002/ijc.32698

Cited by 10 publications

(11 citation statements)

References 49 publications

(86 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Another known LC locus we rediscovered is MPZL2 (also called Epithelial v-like antigen 1, EVA), and the pathogenic frameshift p.I24M fs*22del. MPZL2 is located at 11q23.3, a known GWAS locus for LC 31 , 49 and hearing loss 50 , 51 . MPZL2 is one of the top candidate target genes at this locus based on the expression quantitative trait loci (eQTLs) mapping 31 .…”

Section: Discussionmentioning

confidence: 99%

Rare deleterious germline variants and risk of lung cancer

et al. 2021

Self Cite

View full text Add to dashboard Cite

Recent studies suggest that rare variants exhibit stronger effect sizes and might play a crucial role in the etiology of lung cancers (LC). Whole exome plus targeted sequencing of germline DNA was performed on 1045 LC cases and 885 controls in the discovery set. To unveil the inherited causal variants, we focused on rare and predicted deleterious variants and small indels enriched in cases or controls. Promising candidates were further validated in a series of 26,803 LCs and 555,107 controls. During discovery, we identified 25 rare deleterious variants associated with LC susceptibility, including 13 reported in ClinVar. Of the five validated candidates, we discovered two pathogenic variants in known LC susceptibility loci, ATM p.V2716A (Odds Ratio [OR] 19.55, 95%CI 5.04–75.6) and MPZL2 p.I24M frameshift deletion (OR 3.88, 95%CI 1.71–8.8); and three in novel LC susceptibility genes, POMC c.*28delT at 3′ UTR (OR 4.33, 95%CI 2.03–9.24), STAU2 p.N364M frameshift deletion (OR 4.48, 95%CI 1.73–11.55), and MLNR p.Q334V frameshift deletion (OR 2.69, 95%CI 1.33–5.43). The potential cancer-promoting role of selected candidate genes and variants was further supported by endogenous DNA damage assays. Our analyses led to the identification of new rare deleterious variants with LC susceptibility. However, in-depth mechanistic studies are still needed to evaluate the pathogenic effects of these specific alleles.

show abstract

Section: Discussionmentioning

confidence: 99%

Rare deleterious germline variants and risk of lung cancer

et al. 2021

Self Cite

View full text Add to dashboard Cite

show abstract

“…Apart from SNP markers, we identified a substantial number of insertions, deletions, and CNVs that contribute to our understanding of the complexity of the sorghum genome and the evolutionary processes that result in or develop from that complexity [82]. To date, there are only a few large-scale studies that have evaluated the utility of high-throughput indel data for GWAS and GP in human cohorts, while no such study was found in plants [83, 84]. Detection of SNPs is significantly easier than indel and CNV identification due to sequencing and reference biases, library preparation requirements, and algorithmic artifacts [85, 84].…”

Section: Discussionmentioning

confidence: 99%

“…To date, there are only a few large-scale studies that have evaluated the utility of high-throughput indel data for GWAS and GP in human cohorts, while no such study was found in plants [83, 84]. Detection of SNPs is significantly easier than indel and CNV identification due to sequencing and reference biases, library preparation requirements, and algorithmic artifacts [85, 84]. Indels represent the second-most-common type of genetic variant.…”

Section: Discussionmentioning

confidence: 99%

“…Few studies in sorghum have examined indels and CNVs at scale [86, 87, 61, 88, 89], and none of these demonstrated the comparative value of all three variant types for GWAS. In fact, comparisons across all three variant types are limited to human studies where funds and scalability are less limiting, but even human studies lack a comprehensive review of the topic [83, 84]. Identification of indels and CNVs requires unbiased high-throughput sequencing or long-read sequencing to confidently call variants [90], and as the SAP was sequenced at 38X, this dataset is uniquely suited to obtain high-quality variants of all three types.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Sorghum Association Panel Whole-Genome Sequencing Establishes Pivotal Resource for Dissecting Genomic Diversity

Boatwright

Sapkota

Jin

et al. 2021

Preprint

View full text Add to dashboard Cite

Association mapping panels represent foundational resources for understanding the genetic basis of phenotypic diversity and serve to advance plant breeding by exploring genetic variation across diverse accessions with distinct histories of evolutionary divergence and local adaptation. We report the whole-genome sequencing (WGS) of 400 sorghum [Sorghum bicolor (L.) Moench] accessions from the Sorghum Association Panel (SAP) at an average coverage of 38X (25X-72X), enabling the development of a high-density genomic-marker set of 43,983,694 variants including SNPs (~38 million), indels (~5 million), and CNVs (~170,000). We observe slightly more deletions among indels and a much higher prevalence of deletions among copy number variants compared to insertions. This new marker set enabled the identification of several putatively novel genomic associations for plant height and tannin content, which were not identified when using previous lower-density marker sets. WGS identified and scored variants in 5 kb bins where available genotyping-by-sequencing (GBS) data captured no variants, with half of all bins in the genome falling into this category. The predictive ability of genomic best unbiased linear predictor (GBLUP) models was increased by an average of 30% by using WGS markers rather than GBS markers. We identified 18 selection peaks across subpopulations that formed due to evolutionary divergence during domestication, and we found six Fst peaks resulting from comparisons between converted lines and breeding lines within the SAP that were distinct from the peaks associated with historic selection. This population has been and continues to serve as a significant public resource for sorghum research and demonstrates the value of improving upon existing genomic resources.

show abstract

“…Early detection and individualized treatment require a deeper understanding of the link between lung cancer and this form of inflammation [17]. One of the previous studies investigated the mRNA expression of the interleukins IL-1, IL-6, IL-17, miR-9, and miR-122 as potential useful indicators for non-small cell lung cancer (NSCLC).…”

Section: Fagerstrom Nicotine Dependence Test and Lipopolysaccharide Level Correlationmentioning

confidence: 99%

No Correlation between Fagerstrom Test for Nicotine Dependence Scores to Lipopolysaccharide Marker in Thai Smokers

Pratummas¹,

Sittiprapaporn²,

Chaiyasut³

et al. 2021

International Journal on Advanced Science, Engineering and Information Technology

View full text Add to dashboard Cite

Cigarette smoking is a combination of thousands of synthetic compounds that contribute straightforwardly or by implication to the addiction of cigarette smoking with inflammation, although a lot more may exist. Genome-wide association studies (GWAS) have unequivocally shown that variety in neuronal nicotinic acetylcholine receptor subunit α5 (CHRNA5) and in cytochrome P450 2A6 (CYP2A6) anticipated smoking substantialness, later period of smoking discontinuance. The relationship between the Fagerstrom Test for Nicotine Dependence and the Lipopolysaccharide marker in Thai smokers was proposed in this study. We investigated fourteen Thai smokers in Mahasarakham province who scored 4 or higher on the Fagerstrom Test for Nicotine Dependence. We provided them surveys about their personal information, administered the Fagerstrom Test for Nicotine Dependence, and continued the Lipopolysaccharide marker blood tests. The value of R in Pearson connection was 0.4438. Although it found a positive correlation, the relationship between Fagerstrom Test for Nicotine Dependence and Lipopolysaccharide level was weak due to no correlation. In addition, the value of R2, the coefficient of determination, was 0.197 (p=0.1119). Further studies are needed to investigate more the relationship between smoking and inflammation.

show abstract

Genome‐wide association study of INDELs identified four novel susceptibility loci associated with lung cancer risk

Cited by 10 publications

References 49 publications

Rare deleterious germline variants and risk of lung cancer

Rare deleterious germline variants and risk of lung cancer

Sorghum Association Panel Whole-Genome Sequencing Establishes Pivotal Resource for Dissecting Genomic Diversity

No Correlation between Fagerstrom Test for Nicotine Dependence Scores to Lipopolysaccharide Marker in Thai Smokers

Contact Info

Product

Resources

About