@article {9500,
	title = {Whole Genome Sequencing Based Analysis of Inflammation Biomarkers in the Trans-Omics for Precision Medicine (TOPMed) Consortium.},
	journal = {bioRxiv},
	year = {2023},
	month = {2023 Sep 12},
	abstract = {<p>Inflammation biomarkers can provide valuable insight into the role of inflammatory processes in many diseases and conditions. Sequencing based analyses of such biomarkers can also serve as an exemplar of the genetic architecture of quantitative traits. To evaluate the biological insight, which can be provided by a multi-ancestry, whole-genome based association study, we performed a comprehensive analysis of 21 inflammation biomarkers from up to 38,465 individuals with whole-genome sequencing from the Trans-Omics for Precision Medicine (TOPMed) program. We identified 22 distinct single-variant associations across 6 traits - E-selectin, intercellular adhesion molecule 1, interleukin-6, lipoprotein-associated phospholipase A2 activity and mass, and P-selectin - that remained significant after conditioning on previously identified associations for these inflammatory biomarkers. We further expanded upon known biomarker associations by pairing the single-variant analysis with a rare variant set-based analysis that further identified 19 significant rare variant set-based associations with 5 traits. These signals were distinct from both significant single variant association signals within TOPMed and genetic signals observed in prior studies, demonstrating the complementary value of performing both single and rare variant analyses when analyzing quantitative traits. We also confirm several previously reported signals from semi-quantitative proteomics platforms. Many of these signals demonstrate the extensive allelic heterogeneity and ancestry-differentiated variant-trait associations common for inflammation biomarkers, a characteristic we hypothesize will be increasingly observed with well-powered, large-scale analyses of complex traits.</p>},
	doi = {10.1101/2023.09.10.555215},
	author = {Jiang, Min-Zhi and Gaynor, Sheila M and Li, Xihao and Van Buren, Eric and Stilp, Adrienne and Buth, Erin and Wang, Fei Fei and Manansala, Regina and Gogarten, Stephanie M and Li, Zilin and Polfus, Linda M and Salimi, Shabnam and Bis, Joshua C and Pankratz, Nathan and Yanek, Lisa R and Durda, Peter and Tracy, Russell P and Rich, Stephen S and Rotter, Jerome I and Mitchell, Braxton D and Lewis, Joshua P and Psaty, Bruce M and Pratte, Katherine A and Silverman, Edwin K and Kaplan, Robert C and Avery, Christy and North, Kari and Mathias, Rasika A and Faraday, Nauder and Lin, Honghuang and Wang, Biqi and Carson, April P and Norwood, Arnita F and Gibbs, Richard A and Kooperberg, Charles and Lundin, Jessica and Peters, Ulrike and Dupuis, Jos{\'e}e and Hou, Lifang and Fornage, Myriam and Benjamin, Emelia J and Reiner, Alexander P and Bowler, Russell P and Lin, Xihong and Auer, Paul L and Raffield, Laura M}
}
@article {9866,
	title = {Genomic and phenotypic correlates of mosaic loss of chromosome Y in blood.},
	journal = {Am J Hum Genet},
	volume = {112},
	year = {2025},
	month = {2025 Feb 06},
	pages = {276-290},
	abstract = {<p>Mosaic loss of Y (mLOY) is the most common somatic chromosomal alteration detected in human blood. The presence of mLOY is associated with altered blood cell counts and increased risk of Alzheimer disease, solid tumors, and other age-related diseases. We sought to gain a better understanding of genetic drivers and associated phenotypes of mLOY through analyses of whole-genome sequencing (WGS) of a large set of genetically diverse males from the Trans-Omics for Precision Medicine (TOPMed) program. We show that haplotype-based calling methods can be used with WGS data to successfully identify mLOY events. This approach enabled us to identify differences in mLOY frequencies across populations defined by genetic similarity, revealing a higher frequency of mLOY in the European (EUR) ancestry group compared to other ancestries. We identify multiple loci associated with mLOY susceptibility and show that subsets of human hematopoietic stem cells are enriched for the activity of mLOY susceptibility variants. Finally, we found that certain alleles on chromosome Y are more likely to be lost than others in detectable mLOY clones.</p>},
	keywords = {Alleles, Chromosome Deletion, Chromosomes, Human, Y, Genomics, Haplotypes, Humans, Male, Mosaicism, Phenotype, Whole Genome Sequencing},
	issn = {1537-6605},
	doi = {10.1016/j.ajhg.2024.12.014},
	author = {Jakubek, Yasminka A and Ma, Xiaolong and Stilp, Adrienne M and Yu, Fulong and Bacon, Jason and Wong, Justin W and Aguet, Francois and Ardlie, Kristin and Arnett, Donna K and Barnes, Kathleen and Bis, Joshua C and Blackwell, Tom and Becker, Lewis C and Boerwinkle, Eric and Bowler, Russell P and Budoff, Matthew J and Carson, April P and Chen, Jiawen and Cho, Michael H and Coresh, Josef and Cox, Nancy J and de Vries, Paul S and DeMeo, Dawn L and Fardo, David W and Fornage, Myriam and Guo, Xiuqing and Hall, Michael E and Heard-Costa, Nancy and Hidalgo, Bertha and Irvin, Marguerite Ryan and Johnson, Andrew D and Jorgenson, Eric and Kenny, Eimear E and Kessler, Michael D and Levy, Daniel and Li, Yun and Lima, Jo{\~a}o A C and Liu, Yongmei and Locke, Adam E and Loos, Ruth J F and Machiela, Mitchell J and Mathias, Rasika A and Mitchell, Braxton D and Murabito, Joanne M and Mychaleckyj, Josyf C and North, Kari E and Orchard, Peter and Parker, Stephen C J and Pershad, Yash and Peyser, Patricia A and Pratte, Katherine A and Psaty, Bruce M and Raffield, Laura M and Redline, Susan and Rich, Stephen S and Rotter, Jerome I and Shah, Sanjiv J and Smith, Jennifer A and Smith, Aaron P and Smith, Albert and Taub, Margaret A and Tiwari, Hemant K and Tracy, Russell and Tuftin, Bjoernar and Bick, Alexander G and Sankaran, Vijay G and Reiner, Alexander P and Scheet, Paul and Auer, Paul L}
}
