During the current round of eMERGE the sites were tasked with validating and implementing polygenic risk scores (PRS) in populations with diverse genetic ancestry. The network selected 10 PRS for clinical implementation and return to a 25,000 person cohort, known as the ‘Clinical Implementation Pathway’. The network also is continuing its work on PRS modeling on those conditions not selected for inclusion in the prospective cohort, and refer to those as the ‘Discovery Pathway’. Below you will find links to publications on the PRS models developed over the course of the eMERGE network.
Clinical Implementation Pathway
Asthma
Multiancestral polygenic risk score for pediatric asthma
Namjou B, Lape M, Malolepsza E, DeVore SB, Weirauch MT, Dikilitas O, Jarvik GP, Kiryluk K, Kullo IJ, Liu C, Luo Y, Satterfield BA, Smoller JW, Walunas TL, Connolly J, Sleiman P, Mersha TB, Mentch FD, Hakonarson H, Prows CA, Biagini JM, Khurana Hershey GK, Martin LJ, Kottyan L; eMERGE Network. J Allergy Clin Immunol. 2022 May 18;S0091-6749(22)00660-1.
PMID: 35595084
Breast Cancer
Liu C, Zeinomar N, Chung WK, Kiryluk K, Gharavi AG, Hripcsak G, Crew KD, Shang N, Khan A, Fasel D, Manolio TA, Jarvik GP, Rowley R, Justice AE, Rahm AK, Fullerton SM, Smoller JW, Larson EB, Crane PK, Dikilitas O, Wiesner GL, Bick AG, Terry MB, Weng C. JAMA Netw Open. 2021 Aug 2;4(8):e2119084.
PMID: 34347061
CKD
Genome-wide polygenic score to predict chronic kidney disease across ancestries
Khan A, Turchin MC, Patki A, Srinivasasainagendra V, Shang N, Nadukuru R, Jones AC, Malolepsza E, Dikilitas O, Kullo IJ, Schaid DJ, Karlson E, Ge T, Meigs JB, Smoller JW, Lange C, Crosslin DR, Jarvik GP, Bhatraju PK, Hellwege JN, Chandler P, Torvik LR, Fedotov A, Liu C, Kachulis C, Lennon N, Abul-Husn NS, Cho JH, Ionita-Laza I, Gharavi AG, Chung WK, Hripcsak G, Weng C, Nadkarni G, Irvin MR, Tiwari HK, Kenny EE, Limdi NA, Kiryluk K. Nat Med. 2022 Jun 16. doi: 10.1038/s41591-022-01869-1.
PMID: 35710995
Hyperlipidemia
Accepted at Nature Medicine
Type 2 Diabetes
Validation of a Trans-Ancestry Polygenic Risk Score for Type 2 Diabetes in Diverse Populations
Tian Ge, Amit Patki, Vinodh Srinivasasainagendra, Yen-Feng Lin, Marguerite Ryan Irvin, Hemant K. Tiwari, Nicole Armstrong, Brittney H. Davis, Emma Perez, Vivian Gainer, Barbara Benoit, Mark J. O’Connor, Renuka Narayan, Bethany Etheridge, Maria Stamou, Aaron Leong, Miriam S. Udler, Karmel W. Choi, Ayme D. Miles, Krzysztof Kiryluk, Atlas Khan, Chia-Yen Chen, Yen-Chen Anne Feng, Hailiang Huang, James J. Cimino, Shawn Murphy, Scott T. Weiss, Christoph Lange, Maggie C. Y. Ng, Jordan W. Smoller, Matthew S. Lebo, James B. Meigs, Nita A. Limdi, Elizabeth W. Karlson. Genome Medicine.. 2022 Jun 29;14(1):70. doi: 10.1186/s13073-022-01074-2.
PMID: 35765100
Coronary Heart Disease
Dikilitas O, Schaid DJ, Kosel ML, Carroll RJ, Chute CG, Denny JA, Fedotov A, Feng Q, Hakonarson H, Jarvik GP, Lee MTM, Pacheco JA, Rowley R, Sleiman PM, Stein CM, Sturm AC, Wei WQ, Wiesner GL, Williams MS, Zhang Y, Manolio TA, Kullo IJ. Am J Hum Genet. 2020 May 7;106(5):707-716. doi: 10.1016/j.ajhg.2020.04.002.
PMID: 32386537
PRS was further updated for eMERGE IV. Manuscript to be submitted in July.
Type I Diabetes
Improved genetic risk scoring algorithm for type 1 diabetes prediction
Qu HQ, Qu J, Glessner J, Liu Y, Mentch F, Chang X, March M, Li J, Roizen JD, Connolly JJ, Sleiman P, Hakonarson H. Pediatr Diabetes. 2022 May;23(3):320-323. doi: 10.1111/pedi.13310. Epub 2022 Jan 19.
PMID: 34997821
Obesity/BMI
Planned submission for Fall 2022
Prostate Cancer
Conti DV, Darst BF, Moss LC, Saunders EJ, Sheng X, Chou A, Schumacher FR, Olama AAA, Benlloch S, Dadaev T, Brook MN, Sahimi A, Hoffmann TJ, Takahashi A, Matsuda K, Momozawa Y, Fujita M, Muir K, Lophatananon A, Wan P, Le Marchand L, Wilkens LR, Stevens VL, Gapstur SM, Carter BD, Schleutker J, Tammela TLJ, Sipeky C, Auvinen A, Giles GG, Southey MC, MacInnis RJ, Cybulski C, Wokołorczyk D, Lubiński J, Neal DE, Donovan JL, Hamdy FC, Martin RM, Nordestgaard BG, Nielsen SF, Weischer M, Bojesen SE, Røder MA, Iversen P, Batra J, Chambers S, Moya L, Horvath L, Clements JA, Tilley W, Risbridger GP, Gronberg H, Aly M, Szulkin R, Eklund M, Nordström T, Pashayan N, Dunning AM, Ghoussaini M, Travis RC, Key TJ, Riboli E, Park JY, Sellers TA, Lin HY, Albanes D, Weinstein SJ, Mucci LA, Giovannucci E, Lindstrom S, Kraft P, Hunter DJ, Penney KL, Turman C, Tangen CM, Goodman PJ, Thompson IM Jr, Hamilton RJ, Fleshner NE, Finelli A, Parent MÉ, Stanford JL, Ostrander EA, Geybels MS, Koutros S, Freeman LEB, Stampfer M, Wolk A, Håkansson N, Andriole GL, Hoover RN, Machiela MJ, Sørensen KD, Borre M, Blot WJ, Zheng W, Yeboah ED, Mensah JE, Lu YJ, Zhang HW, Feng N, Mao X, Wu Y, Zhao SC, Sun Z, Thibodeau SN, McDonnell SK, Schaid DJ, West CML, Burnet N, Barnett G, Maier C, Schnoeller T, Luedeke M, Kibel AS, Drake BF, Cussenot O, Cancel-Tassin G, Menegaux F, Truong T, Koudou YA, John EM, Grindedal EM, Maehle L, Khaw KT, Ingles SA, Stern MC, Vega A, Gómez-Caamaño A, Fachal L, Rosenstein BS, Kerns SL, Ostrer H, Teixeira MR, Paulo P, Brandão A, Watya S, Lubwama A, Bensen JT, Fontham ETH, Mohler J, Taylor JA, Kogevinas M, Llorca J, Castaño-Vinyals G, Cannon-Albright L, Teerlink CC, Huff CD, Strom SS, Multigner L, Blanchet P, Brureau L, Kaneva R, Slavov C, Mitev V, Leach RJ, Weaver B, Brenner H, Cuk K, Holleczek B, Saum KU, Klein EA, Hsing AW, Kittles RA, Murphy AB, Logothetis CJ, Kim J, Neuhausen SL, Steele L, Ding YC, Isaacs WB, Nemesure B, Hennis AJM, Carpten J, Pandha H, Michael A, De Ruyck K, De Meerleer G, Ost P, Xu J, Razack A, Lim J, Teo SH, Newcomb LF, Lin DW, Fowke JH, Neslund-Dudas C, Rybicki BA, Gamulin M, Lessel D, Kulis T, Usmani N, Singhal S, Parliament M, Claessens F, Joniau S, Van den Broeck T, Gago-Dominguez M, Castelao JE, Martinez ME, Larkin S, Townsend PA, Aukim-Hastie C, Bush WS, Aldrich MC, Crawford DC, Srivastava S, Cullen JC, Petrovics G, Casey G, Roobol MJ, Jenster G, van Schaik RHN, Hu JJ, Sanderson M, Varma R, McKean-Cowdin R, Torres M, Mancuso N, Berndt SI, Van Den Eeden SK, Easton DF, Chanock SJ, Cook MB, Wiklund F, Nakagawa H, Witte JS, Eeles RA, Kote-Jarai Z, Haiman CA. Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction. Nat Genet. 2021 Jan;53(1):65-75. doi: 10.1038/s41588-020-00748-0. Epub 2021 Jan 4. Erratum in: Nat Genet. 2021 Jan 20; PMCID: PMC8148035
PMID: 33398198
Based on transancestral PRS published and developed outside of eMERGE: https://pubmed.ncbi.nlm.nih.gov/33398198/
Flagship PRS manuscript – overarching eMERGE paper on PRS selection and development
Selection, optimization, and validation of polygenic risk scores for clinical implementation in diverse populations. Under development with anticipated submission in Sept 2022. Evaluation of the utility of the All of Us Research Program participant data to construct an ancestry calibration model for the eMERGE IV PRS analytical pipeline under development.
Discovery Pathway
Uterine fibroids
Uterine fibroid polygenic risk score (PRS) associates and predicts risk for uterine fibroid
Piekos JA, Hellwege JN, Zhang Y, Torstenson ES, Jarvik GP, Dikilitas O, Kullo IJ, Schaid DJ, Crosslin DR, Pendergrass SA, Lee MTM, Roden D, Denny JC, Edwards TL, Velez Edwards DR. Hum Genet. 2022 Feb 28. doi: 10.1007/s00439-022-02442-z. PMID: 35226188
Colorectal Cancer
Genome-wide Modeling of Polygenic Risk Score in Colorectal Cancer Risk
Thomas M, Sakoda LC, Hoffmeister M, Rosenthal EA, Lee JK, van Duijnhoven FJB, Platz EA, Wu AH, Dampier CH, de la Chapelle A, Wolk A, Joshi AD, Burnett-Hartman A, Gsur A, Lindblom A, Castells A, Win AK, Namjou B, Van Guelpen B, Tangen CM, He Q, Li CI, Schafmayer C, Joshu CE, Ulrich CM, Bishop DT, Buchanan DD, Schaid D, Drew DA, Muller DC, Duggan D, Crosslin DR, Albanes D, Giovannucci EL, Larson E, Qu F, Mentch F, Giles GG, Hakonarson H, Hampel H, Stanaway IB, Figueiredo JC, Huyghe JR, Minnier J, Chang-Claude J, Hampe J, Harley JB, Visvanathan K, Curtis KR, Offit K, Li L, Le Marchand L, Vodickova L, Gunter MJ, Jenkins MA, Slattery ML, Lemire M, Woods MO, Song M, Murphy N, Lindor NM, Dikilitas O, Pharoah PDP, Campbell PT, Newcomb PA, Milne RL, MacInnis RJ, Castellví-Bel S, Ogino S, Berndt SI, Bézieau S, Thibodeau SN, Gallinger SJ, Zaidi SH, Harrison TA, Keku TO, Hudson TJ, Vymetalkova V, Moreno V, Martín V, Arndt V, Wei WQ, Chung W, Su YR, Hayes RB, White E, Vodicka P, Casey G, Gruber SB, Schoen RE, Chan AT, Potter JD, Brenner H, Jarvik GP, Corley DA, Peters U, Hsu L. Am J Hum Genet. 2020 Sep 3;107(3):432-444.
PMID: 32758450