Genome-wide association testing beyond SNPs

Harris, Laura; McDonagh, Ellen M.; Zhang, Xiaolei; Fawcett, Katherine; Foreman, Amy; Daneck, Petr; Sergouniotis, Panagiotis I.; Parkinson, Helen; Mazzarotto, Francesco; Inouye, Michael; Hollox, Edward J.; Birney, Ewan; Fitzgerald, Tomas

doi:10.1038/s41576-024-00778-y

Cited by 3 publications

References 168 publications

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The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

Cerezo,

Sollis,

et al. 2024

Nucleic Acids Research

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The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7 000 publications for >15 000 traits, from which more than 625 000 lead associations have been curated. Additionally, 85 000 full genome-wide summary statistics datasets—containing association data for all variants in the analysis—are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.

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The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

Cerezo,

Sollis,

et al. 2024

Nucleic Acids Research

View full text Add to dashboard Cite

show abstract

The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

Cerezo,

Sollis,

et al. 2024

Preprint

View full text Add to dashboard Cite

The NHGRI-EBI GWAS Catalog serves as a vital resource for the genetic research community, providing access to the most comprehensive database of human GWAS results. Currently, it contains close to 7,000 publications for more than 15,000 traits, from which more than 625,000 lead associations have been curated. Additionally, 85,000 full genome-wide summary statistics datasets - containing association data for all variants in the analysis - are available for downstream analyses such as meta-analysis, fine-mapping, Mendelian randomisation or development of polygenic risk scores. As a centralised repository for GWAS results, the GWAS Catalog sets and implements standards for data submission and harmonisation, and encourages the use of consistent descriptors for traits, samples and methodologies. We share processes and vocabulary with the PGS Catalog, improving interoperability for a growing user group. Here, we describe the latest changes in data content, improvements in our user interface, and the implementation of the GWAS-SSF standard format for summary statistics. We address the challenges of handling the rapid increase in large-scale molecular quantitative trait GWAS and the need for sensitivity in the use of population and cohort descriptors while maintaining data interoperability and reusability.

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Integer programming framework for pangenome-based genome inference

Chandra,

Hossen,

Scholz

et al. 2024

Preprint

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Affordable genotyping methods are essential in genomics. Commonly used genotyping methods primarily support single nucleotide variants and short indels but neglect structural variants. Additionally, accuracy of read alignments to a reference genome is unreliable in highly polymorphic and repetitive regions, further impacting genotyping performance. Recent works highlight the advantage of haplotype-resolved pangenome graphs in addressing these challenges. Building on these developments, we propose a rigorous alignment-free genotyping framework. Our formulation seeks a path through the pangenome graph that maximizes the matches between the path and substrings of sequencing reads (e.g., k-mers) while minimizing recombination events (haplotype switches) along the path. We prove that this problem is NP-Hard and develop efficient integer-programming solutions. We benchmarked the algorithm using downsampled short-read datasets from homozygous human cell lines with coverage ranging from 0.1x to 10x. Our algorithm accurately estimates complete major histocompatibility complex (MHC) haplotype sequences with small edit distances from the ground-truth sequences, providing a significant advantage over existing methods on low-coverage inputs. Although our algorithm is designed for haploid samples, we discuss future extensions to diploid samples. Implementation: https://github.com/at-cg/PHI

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Genome-wide association testing beyond SNPs

Cited by 3 publications

References 168 publications

The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

The NHGRI-EBI GWAS Catalog: standards for reusability, sustainability and diversity

Integer programming framework for pangenome-based genome inference

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