GRiD (Genomic Repeat inference from Depth) is a haplotype-length estimator for VNTR and CNV regions from short-read whole-genome sequencing data. GRiD integrates normalized read depth, nearest-neighbor coverage profiles, and haplotype sharing (IBD/IBS) to infer diploid repeat copy number and resolve chromosome-specific repeat lengths.
View the source code on GitHub or explore the full documentation on ReadTheDocs.
Acknowledgments Further
This work was conducted in the Stanislawski lab at the University of Colorado Anschutz. Computational resources were provided by the NIH BioData Catalyst and the University of North Carolina Chapel Hill Research Computing facilities. In addition to all co-authors, we thank Drs. Jonathan Shortt and Esteban Lucero for their help and guidance.
References
References correspond to numbered citations in the conference poster
-
Tsimikas S, Hall JL. Lipoprotein (a) as a potential causal genetic risk factor of cardiovascular disease: a rationale for increased efforts to understand its pathophysiology and develop targeted therapies. Journal of the American College of Cardiology. 2012;60(8):716–721.
-
Lamon-Fava S, Jimenez D, Christian JC, Fabsitz RR, Reed T, Carmelli D, Castelli WP, Ordovas JM, Wilson PWF, Schaefer EJ. The NHLBI Twin Study: heritability of apolipoprotein AI, B, and low density lipoprotein subclasses and concordance for lipoprotein (a). Atherosclerosis. 1991;91(1–2):97–106.
-
Reyes-Soffer G, Ginsberg HN, Berglund L, Duell PB, Heffron SP, Kamstrup PR, Lloyd-Jones DM, Marcovina SM, Yeang C, Koschinsky ML, et al. Lipoprotein (a): a genetically determined, causal, and prevalent risk factor for atherosclerotic cardiovascular disease. Arteriosclerosis, Thrombosis, and Vascular Biology. 2022;42(1):e48–e60.
-
Ramsis M, Naguib M, Dzotsi M, Wilkinson M, Mahmud E, Taub P, Bhatia HS. Lipoprotein (a) testing trends in the United States 2015–2024: an analysis of 300 million individuals. JACC: Advances. 2025;4(11 Pt 1):102205.
-
Kronenberg F, Mora S, Stroes ESG, Ference BA, Arsenault BJ, Berglund L, Dweck MR, Koschinsky M, Lambert G, Mach F, et al. Lipoprotein (a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement. European Heart Journal. 2022;43(39):3925–3946.
-
Marcovina SM, Albers JJ. Lipoprotein (a) measurements for clinical application. Journal of Lipid Research. 2016;57(4):526–537.
-
Tsimikas S, Karwatowska-Prokopczuk E, Gouni-Berthold I, Tardif JC, Baum SJ, Steinhagen-Thiessen E, Shapiro MD, Stroes ES, Moriarty PM, Nordestgaard BG, et al. Lipoprotein (a) reduction in persons with cardiovascular disease. New England Journal of Medicine. 2020;382(3):244–255.
-
Graham MJ, Viney N, Crooke RM, Tsimikas S. Antisense inhibition of apolipoprotein (a) to lower plasma lipoprotein (a) levels in humans. Journal of Lipid Research. 2016;57(3):340–351.
-
Swerdlow DI, Rider DA, Yavari A, Wikström Lindholm M, Campion GV, Nissen SE. Treatment and prevention of lipoprotein (a)-mediated cardiovascular disease: the emerging potential of RNA interference therapeutics. Cardiovascular Research. 2022;118(5):1218–1231.
-
Schmidt K, Noureen A, Kronenberg F, Utermann G. Structure, function, and genetics of lipoprotein (a). Journal of Lipid Research. 2016;57(8):1339–1359.
-
Utermann G, Menzel HJ, Kraft HG, Duba HC, Kemmler HG, Seitz C, et al. Lp(a) glycoprotein phenotypes: inheritance and relation to Lp(a)-lipoprotein concentrations in plasma. Journal of Clinical Investigation. 1987;80(2):458–465.
-
Clarke R, Peden JF, Hopewell JC, Kyriakou T, Goel A, Heath SC, Parish S, Barlera S, Franzosi MG, Rust S, et al. Genetic variants associated with Lp(a) lipoprotein level and coronary disease. New England Journal of Medicine. 2009;361(26):2518–2528.
-
Kamstrup PR. Lipoprotein (a) and ischemic heart disease—a causal association? Atherosclerosis. 2010;211(1):15–23.
-
Saeedi R, Frohlich J. Lipoprotein (a), an independent cardiovascular risk marker. Clinical Diabetes and Endocrinology. 2016;2:7.
-
Marcovina SM, Koschinsky ML, Albers JJ, Skarlatos S. Report of the NHLBI Workshop on Lipoprotein (a) and Cardiovascular Disease: recent advances and future directions. Clinical Chemistry. 2003;49(11):1785–1796.
-
White AL, Hixson JE, Rainwater DL, Lanford RE. Molecular basis for “null” lipoprotein (a) phenotypes and the influence of apolipoprotein (a) size on plasma lipoprotein (a) level in the baboon. Journal of Biological Chemistry. 1994;269(12):9060–9066.
-
Coassin S, Kronenberg F. Lipoprotein (a) beyond the kringle IV repeat polymorphism: the complexity of genetic variation in the LPA gene. Atherosclerosis. 2022;349:17–35.
-
Mukamel RE, Handsaker RE, Sherman MA, Barton AR, Zheng Y, McCarroll SA, Loh PR. Protein-coding repeat polymorphisms strongly shape diverse human phenotypes. Science. 2021;373(6562):1499–1505.
-
Sinnott-Armstrong N, Tanigawa Y, Amar D, Mars N, Benner C, Aguirre M, Venkataraman GR, Wainberg M, Ollila HM, Kiiskinen T, et al. Genetics of 35 blood and urine biomarkers in the UK Biobank. Nature Genetics. 2021;53(2):185–194.
-
Xie T, Wang B, Nolte IM, van der Most PJ, Oldehinkel AJ, Hartman CA, Snieder H. Genetic risk scores for complex disease traits in youth. Circulation: Genomic and Precision Medicine. 2020;13(4):e002775.
-
Trinder M, Uddin MM, Finneran P, Aragam KG, Natarajan P. Clinical utility of lipoprotein (a) and LPA genetic risk score in risk prediction of incident atherosclerotic cardiovascular disease. JAMA Cardiology. 2021;6(3):287–295.
-
Dron JS, Wang M, Patel AP, Kartoun U, Ng K, Hegele RA, Khera AV. Genetic predictor to identify individuals with high lipoprotein (a) concentrations. Circulation: Genomic and Precision Medicine. 2021;14(1):e003182.
-
Lee MP, Dimos SF, Raffield LM, Wang Z, Ballou AF, Downie CG, Arehart CH, Correa A, De Vries PS, Du Z, et al. Ancestral diversity in lipoprotein (a) studies helps address evidence gaps. Open Heart. 2023;10(2):e002382.
-
Hilmarsson H, Kumar AS, Rastogi R, Bustamante CD, Mas Montserrat D, Ioannidis AG. High resolution ancestry deconvolution for next generation genomic data. bioRxiv. 2021.
-
Shemirani R, Belbin GM, Avery CL, Kenny EE, Gignoux CR, Ambite JL. Rapid detection of identity-by-descent tracts for mega-scale datasets. Nature Communications. 2021;12:3546.