Tsao CW, Aday AW, Almarzooq ZI, Anderson CAM, Arora P, Avery CL, et al. Heart disease and stroke statistics—2023 update: a report from the American Heart Association. Circulation. 2023;147:e93-621.

Article  PubMed  Google Scholar 

Mensah GA, Roth GA, Fuster V. The global burden of cardiovascular diseases and risk factors. J Am Coll Cardiol. 2019;74:2529–32.

Article  PubMed  Google Scholar 

Zhou W, Kanai M, Wu K-HH, Rasheed H, Tsuo K, Hirbo JB, et al. Global Biobank Meta-analysis Initiative: powering genetic discovery across human disease. Cell Genomics. 2022;2:100192.

Article  CAS  PubMed  PubMed Central  Google Scholar 

The “All of Us” research program. N Engl J Med. 2019;381:668–76.

Bycroft C, Freeman C, Petkova D, Band G, Elliott LT, Sharp K, et al. The UK Biobank resource with deep phenotyping and genomic data. Nature. 2018;562:203–9.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Wouters OJ, McKee M, Luyten J. Estimated research and development investment Needed to Bring a New Medicine to Market, 2009–2018. JAMA. 2020;323:844–53.

Article  PubMed  PubMed Central  Google Scholar 

Schuhmacher A, Hinder M, Von Stegmann Und Stein A, Hartl D, Gassmann O. Analysis of pharma R&D productivity – a new perspective needed. Drug Discov Today. 2023;28:103726.

Article  PubMed  Google Scholar 

Moore TJ, Zhang H, Anderson G, Alexander GC. Estimated costs of pivotal trials for novel therapeutic agents approved by the US Food and Drug Administration, 2015–2016. JAMA Intern Med. 2018;178:1451–7.

Article  PubMed  PubMed Central  Google Scholar 

Harrison RK. Phase II and phase III failures: 2013–2015. Nat Rev Drug Discov. 2016;15:817–8.

Article  CAS  PubMed  Google Scholar 

Arrowsmith J, Miller P. Trial watch: phase II and phase III attrition rates 2011–2012. Nat Rev Drug Discov. 2013;12:569.

Article  CAS  PubMed  Google Scholar 

El Khoury P, Elbitar S, Ghaleb Y, Khalil YA, Varret M, Boileau C, et al. PCSK9 mutations in familial hypercholesterolemia: from a groundbreaking discovery to anti-PCSK9 therapies. Curr Atheroscler Rep. 2017;19:49.

Article  PubMed  Google Scholar 

• Trajanoska K, Bhérer C, Taliun D, Zhou S, Richards JB, Mooser V. From target discovery to clinical drug development with human genetics. Nature. 2023;620:737–45. This review paper details the process of translating genetic discoveries into clinical drug development.

Article  ADS  CAS  PubMed  Google Scholar 

Nelson MR, Tipney H, Painter JL, Shen J, Nicoletti P, Shen Y, et al. The support of human genetic evidence for approved drug indications. Nat Genet. 2015;47:856–60.

Article  CAS  PubMed  Google Scholar 

King EA, Davis JW, Degner JF. Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval. PLOS Genet. 2019;15:e1008489.

Article  PubMed  PubMed Central  Google Scholar 

Abifadel M, Varret M, Rabès J-P, Allard D, Ouguerram K, Devillers M, et al. Mutations in PCSK9 cause autosomal dominant hypercholesterolemia. Nat Genet. 2003;34:154–6.

Article  CAS  PubMed  Google Scholar 

Musunuru K, Pirruccello JP, Do R, Peloso GM, Guiducci C, Sougnez C, et al. Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med. 2010;363:2220–7.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Schmidt AF, Hingorani AD, Finan C. Human genomics and drug development. Cold Spring Harb Perspect Med [Internet]. 2022 [cited 2023 Dec 12];12. Available from: https://doi.org/10.1101/cshperspect.a039230

•• Carss KJ, Deaton AM, Del Rio-Espinola A, Diogo D, Fielden M, Kulkarni DA, et al. Using human genetics to improve safety assessment of therapeutics. Nat Rev Drug Discov. 2023;22:145–62. This review paper highlights the role of human genetics in enhancing the safety assessment of therapeutics, which is pivotal in advancing the development of drugs that are both effective and safe.

Article  CAS  PubMed  Google Scholar 

Emdin CA, Khera AV, Kathiresan S. Mendelian randomization. JAMA. 2017;318:1925–6.

Article  PubMed  Google Scholar 

• Nissen SE, Linnebjerg H, Shen X, Wolski K, Ma X, Lim S, et al. Lepodisiran, an extended-duration short interfering RNA targeting lipoprotein(a): a randomized dose-ascending clinical trial. JAMA [Internet]. 2023 [cited 2023 Nov 26]; Available from: https://doi.org/10.1001/jama.2023.21835. Findings from this study offer critical insights into the efficacy of extended-duration RNA interference therapies in targeting lipoprotein(a) paving the way for novel therapeutic approaches in the cardiometabolic field.

A single infusion of a gene-editing medicine may control inherited high LDL cholesterol. Am Heart Assoc [Internet]. 2023 [cited 2023 Nov 26]; Available from: https://newsroom.heart.org/news/a-single-infusion-of-a-gene-editing-medicine-may-control-inherited-high-ldl-cholesterol

•• Fahed AC, Philippakis AA, Khera AV. The potential of polygenic scores to improve cost and efficiency of clinical trials. Nat Commun. 2022;13:1–4. This article demonstrates the potential of polygenic scores in enhancing the cost-efficiency and effectiveness of clinical trials.

Article  Google Scholar 

Precision Cardiology Laboratory [Internet]. Broad Inst. 2018 [cited 2023 Dec 12]. Available from: https://www.broadinstitute.org/precision-cardiology-laboratory

Regeneron Genetics Center (RGC): genetics to therapeutics [Internet]. 2023 [cited 2023 Dec 12]. Available from: https://www.regeneron.com/science/genetics-center

Alcalai R, Seidman JG, Seidman CE. Genetic basis of hypertrophic cardiomyopathy: from bench to the clinics. J Cardiovasc Electrophysiol. 2008;19:104–10.

Article  PubMed  Google Scholar 

Lu W, Gauthier LD, Poterba T, Giacopuzzi E, Goodrich JK, Stevens CR, et al. CHARR efficiently estimates contamination from DNA sequencing data [Internet]. bioRxiv; 2023 [cited 2023 Dec 12]. p. 2023.06.28.545801. Available from: https://www.biorxiv.org/content/10.1101/2023.06.28.545801v1

Koenig Z, Yohannes MT, Nkambule LL, Goodrich JK, Kim HA, Zhao X, et al. A harmonized public resource of deeply sequenced diverse human genomes [Internet]. bioRxiv; 2023 [cited 2023 Dec 12]. p. 2023.01.23.525248. Available from: https://www.biorxiv.org/content/10.1101/2023.01.23.525248v3

Bergström A, McCarthy SA, Hui R, Almarri MA, Ayub Q, Danecek P, et al. Insights into human genetic variation and population history from 929 diverse genomes. Science. 2020;367:eaay5012.

Article  PubMed  PubMed Central  Google Scholar 

Raal FJ, Rosenson RS, Reeskamp LF, Hovingh GK, Kastelein JJP, Rubba P, et al. Evinacumab for Homozygous Familial Hypercholesterolemia. N Engl J Med. 2020;383:711–20.

Article  CAS  PubMed  Google Scholar 

Sabatine MS, Giugliano RP, Keech AC, Honarpour N, Wiviott SD, Murphy SA, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376:1713–22.

Article  CAS  PubMed  Google Scholar 

Schwartz GG, Steg PG, Szarek M, Bhatt DL, Bittner VA, Diaz R, et al. Alirocumab and cardiovascular outcomes after acute coronary syndrome. N Engl J Med. 2018;379:2097–107.

Article  CAS  PubMed  Google Scholar 

Geisterfer-Lowrance AA, Kass S, Tanigawa G, Vosberg HP, McKenna W, Seidman CE, et al. A molecular basis for familial hypertrophic cardiomyopathy: a beta cardiac myosin heavy chain gene missense mutation. Cell. 1990;62:999–1006.

Article  CAS  PubMed  Google Scholar 

Marian AJ. Molecular genetic basis of hypertrophic cardiomyopathy. Circ Res. 2021;128:1533–53.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Olivotto I, Oreziak A, Barriales-Villa R, Abraham TP, Masri A, Garcia-Pavia P, et al. Mavacamten for treatment of symptomatic obstructive hypertrophic cardiomyopathy (EXPLORER-HCM): a randomised, double-blind, placebo-controlled, phase 3 trial. Lancet. 2020;396:759–69.

Article  CAS  PubMed  Google Scholar 

Baxter SM, Posey JE, Lake NJ, Sobreira N, Chong JX, Buyske S, et al. Centers for Mendelian Genomics: a decade of facilitating gene discovery. Genet Med. 2022;24:784–97.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Posey JE, O’Donnell-Luria AH, Chong JX, Harel T, Jhangiani SN, Coban Akdemir ZH, et al. Insights into genetics, human biology and disease gleaned from family based genomic studies. Genet Med. 2019;21:798–812.

Article  PubMed  PubMed Central  Google Scholar 

Aragam KG, Jiang T, Goel A, Kanoni S, Wolford BN, Atri DS, et al. Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants. Nat Genet. 2022;54:1803–15.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Graham SE, Clarke SL, Wu K-HH, Kanoni S, Zajac GJM, Ramdas S, et al. The power of genetic diversity in genome-wide association studies of lipids. Nature. 2021;600:675–9.

Article  ADS  CAS  PubMed  PubMed Central  Google Scholar 

Evangelou E, Warren HR, Mosen-Ansorena D, Mifsud B, Pazoki R, Gao H, et al. Genetic analysis of over 1 million people identifies 535 new loci associated with blood pressure traits. Nat Genet. 2018;50:1412–25.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mahajan A, Spracklen CN, Zhang W, Ng MCY, Petty LE, Kitajima H, et al. Multi-ancestry genetic study of type 2 diabetes highlights the power of diverse populations for discovery and translation. Nat Genet. 2022;54:560–72.

Article  CAS  PubMed  PubMed Central  Google Scholar 

Mizoguchi T, MacDonald BT, Bhandary B, Popp NR, Laprise D, Arduini A, et al. Coronary disease association with ADAMTS7 is due to protease activity. Circ Res. 2021;129:458–70.

Article