PRS-on-Spark (PRSoS): a novel, efficient and flexible approach for generating polygenic risk scores View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Lawrence M. Chen, Nelson Yao, Elika Garg, Yuecai Zhu, Thao T. T. Nguyen, Irina Pokhvisneva, Shantala A. Hari Dass, Eva Unternaehrer, Hélène Gaudreau, Marie Forest, Lisa M. McEwen, Julia L. MacIsaac, Michael S. Kobor, Celia M. T. Greenwood, Patricia P. Silveira, Michael J. Meaney, Kieran J. O’Donnell

ABSTRACT

BACKGROUND: Polygenic risk scores (PRS) describe the genomic contribution to complex phenotypes and consistently account for a larger proportion of variance in outcome than single nucleotide polymorphisms (SNPs) alone. However, there is little consensus on the optimal data input for generating PRS, and existing approaches largely preclude the use of imputed posterior probabilities and strand-ambiguous SNPs i.e., A/T or C/G polymorphisms. Our ability to predict complex traits that arise from the additive effects of a large number of SNPs would likely benefit from a more inclusive approach. RESULTS: We developed PRS-on-Spark (PRSoS), a software implemented in Apache Spark and Python that accommodates different data inputs and strand-ambiguous SNPs to calculate PRS. We compared performance between PRSoS and an existing software (PRSice v1.25) for generating PRS for major depressive disorder using a community cohort (N = 264). We found PRSoS to perform faster than PRSice v1.25 when PRS were generated for a large number of SNPs (~ 17 million SNPs; t = 42.865, p = 5.43E-04). We also show that the use of imputed posterior probabilities and the inclusion of strand-ambiguous SNPs increase the proportion of variance explained by a PRS for major depressive disorder (from 4.3% to 4.8%). CONCLUSIONS: PRSoS provides the user with the ability to generate PRS using an inclusive and efficient approach that considers a larger number of SNPs than conventional approaches. We show that a PRS for major depressive disorder that includes strand-ambiguous SNPs, calculated using PRSoS, accounts for the largest proportion of variance in symptoms of depression in a community cohort, demonstrating the utility of this approach. The availability of this software will help users develop more informative PRS for a variety of complex phenotypes. More... »

PAGES

295

Identifiers

URI

http://scigraph.springernature.com/pub.10.1186/s12859-018-2289-9

DOI

http://dx.doi.org/10.1186/s12859-018-2289-9

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1106053203

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/30089455


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270 https://www.grid.ac/institutes/grid.17091.3e schema:alternateName University of British Columbia
271 schema:name Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada
272 rdf:type schema:Organization
273 https://www.grid.ac/institutes/grid.414980.0 schema:alternateName Jewish General Hospital
274 schema:name Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, Quebec, Canada
275 Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, QC, Canada
276 rdf:type schema:Organization
277 https://www.grid.ac/institutes/grid.440050.5 schema:alternateName Canadian Institute for Advanced Research
278 schema:name Child and Brain Development Program, Canadian Institute for Advanced Research (CIFAR), Toronto, ON, Canada
279 Department of Psychiatry, McGill University, Montreal, Quebec, Canada
280 Douglas Hospital Research Centre, McGill University, H4H1R3, Montreal, Quebec, Canada
281 Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, QC, Canada
282 Sackler Program for Epigenetics & Psychobiology, McGill University, Montreal, Quebec, Canada
283 rdf:type schema:Organization
284 https://www.grid.ac/institutes/grid.452264.3 schema:alternateName Singapore Institute for Clinical Sciences
285 schema:name Child and Brain Development Program, Canadian Institute for Advanced Research (CIFAR), Toronto, ON, Canada
286 Department of Psychiatry, McGill University, Montreal, Quebec, Canada
287 Douglas Hospital Research Centre, McGill University, H4H1R3, Montreal, Quebec, Canada
288 Ludmer Centre for Neuroinformatics and Mental Health, McGill University, Montreal, QC, Canada
289 Sackler Program for Epigenetics & Psychobiology, McGill University, Montreal, Quebec, Canada
290 Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore
291 rdf:type schema:Organization
 




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