polygenic risk

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24 papers

Heterogeneous endocrine cell composition defines human islet functional phenotypes

Carmella Evans‐Molina, Yasminye D. Pettway, Diane C. Saunders, Seth A. Sharp, Thomas S. R. Bate, Han Sun, Heather H. Durai, Shaojun Mei, Anastasia Coldren, Corey Davis, Conrad Reihsmann, Alexander L. Hopkirk, Jay Taylor, Amber M. Bradley, Radhika Aramandla, , Marcela Briššová

In 299 islet preparations from donors without diabetes, endocrine cell composition, not donor demographics, tracked insulin secretion, and δ cell percentage rose with type 2 diabetes genetic risk.

Nature Communications · May 12, 2026Peer-reviewedPhysiology✦ In-depth digest

Ancient regulatory evolution shapes individual language abilities in present-day humans

Lucas G. Casten, Tanner Koomar, Taylor Thomas, Jin‐Young Koh, Dabney Hofammann, Savantha Thenuwara, Allison M. Momany, Marlea O’Brien, Jeffrey Clark Murray, J. Bruce Tomblin, Jacob J. Michaelson

Polygenic score variants in HAQERs (Human Ancestor Quickly Evolved Regions, <0.1% of the genome) predict spoken language but not nonverbal IQ; language associations replicate in SPARK, ABCD and UK Biobank.

Science Advances · Apr 22, 2026Peer-reviewedEvolutionary Biology✦ In-depth digest

Decomposition of phenotypic heterogeneity in autism reveals distinct and coherent genetic programs

Aviya Litman, Natalie Sauerwald, LeeAnne Green Snyder, Jennifer H. Foss‐Feig, Christopher Y. Park, Yun Hao, Ilan Dinstein, Chandra L. Theesfeld, Olga G. Troyanskaya

Mixture modeling of 239 phenotype features in 5,392 SPARK autistic children defines four replicable classes carrying distinct common and rare variant signatures and developmental gene-timing patterns.

Nature Genetics · Jul 1, 2025Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

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

María Cerezo, Elliot Sollis, Yue Ji, Elizabeth Lewis, Ala Abid, Karatuğ Ozan Bircan, Peggy Hall, James D. Hayhurst, Sajo John, Abayomi Mosaku, Santhi Ramachandran, Amy Foreman, Arwa Ibrahim, James Alastair McLaughlin, Zoë May Pendlington, , Laura Wiseman Harris

The GWAS Catalog now holds 625,113 curated SNP-trait associations from 6,921 publications plus >85K summary statistics datasets, with a new GWAS-SSF submission standard and GRCh38 harmonisation.

Nucleic Acids Research · Oct 22, 2024Peer-reviewedGenetics✦ In-depth digest

Family-GWAS reveals effects of environment and mating on genetic associations

Tammy Tan, Hariharan Jayashankar, Junming Guan, Seyed Moeen Nehzati, Mahdi Mir, Michael Bennett, Esben Agerbo, Rafael Ahlskog, Ville Anapaz, Stefania Benónísdóttir, Dorret Irene Boomsma, Archie I Campbell, Christopher F. Chabris, Zhengming Chen, China Kadoorie Biobank Collaborative Group, , Alexander I. Young

Family-based GWAS meta-analysis of 34 phenotypes shows standard GWAS effects carry sizeable confounding uncorrelated with direct genetic effects, while assortative mating likely inflates SNP heritability and genetic correlations.

medRxiv · Oct 1, 2024 · PreprintGenetic & Genomic Medicine✦ In-depth digest

Integrative polygenic risk score improves the prediction accuracy of complex traits and diseases

Buu Minh Thanh Truong, Leland E. Hull, Yunfeng Ruan, Qin Huang, Whitney Hornsby, Hilary C. Martin, David A. van Heel, Ying Wang, Alicia R. Martin, Sang Lee, Pradeep Natarajan

Cross-trait Elastic Net mixing of PGS Catalog scores (PRSmix+) lifted mean PRS accuracy 1.72-fold in Europeans and 1.42-fold in South Asians over the best single score.

Cell Genomics · Mar 19, 2024Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

Genome-wide Association Identifies Novel Etiological Insights Associated with Parkinsons Disease in African and African Admixed Populations

Mie Rizig, Sara Bandrés‐Ciga, Mary B. Makarious, Oluwadamilola Omolara Ojo, Peter Wild Crea, Oladunni Abiodun, Kristin S. Levine, Sani Abubakar, Charles Achoru, Dan Vitale, Olaleye Akinmola Adeniji, Osigwe Paul Agabi, Mathew J. Koretsky, Uchechi Agulanna, Deborah A Hall, , Francis Ojini

Intronic GBA1 variant rs3115534-G, common in African and African admixed ancestry but rare elsewhere, raises Parkinson's disease risk (OR 1.58) and lowers onset age.

The Lancet Neurology · Nov 1, 2023Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

Global Biobank Meta-analysis Initiative: powering genetic discovery across human diseases

Wei Zhou, Masahiro Kanai, Kuan-Han Wu, Humaira Rasheed, Kristin Tsuo, Jibril B Hirbo, Ying Wang, Arjun Bhattacharya, Huiling Zhao, Shinichi Namba, Ida L. Surakka, Brooke N. Wolford, Valeria Lo Faro, Esteban A. Lopera-Maya, Kristi Läll, , Jennifer E. Huffman

Meta-analysis of harmonized GWAS from up to 18 biobanks (six ancestry groups) across 14 endpoints replicated 320 known loci and identified 188 apparently novel loci.

Cell Genomics · Oct 1, 2022Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

Mapping genomic loci prioritises genes and implicates synaptic biology in schizophrenia

Vassily Trubetskoy, Antonio F. Pardiñas, Ting Qi, Georgia Panagiotaropoulou, Swapnil Awasthi, Tim B. Bigdeli, Julien Bryois, Chia‐Yen Chen, Charlotte A. Dennison, Lynsey S. Hall, Max Lam, Kyoko Watanabe, Oleksandr Frei, Tian Ge, Janet C Harwood, , Elliot S. Gershon

A genome-wide association study of 69,369 schizophrenia cases and 236,642 controls identifies 270 risk loci, prioritizes 130 genes, and links common and rare risk variants to neuronal synaptic biology.

Nature · Apr 8, 2022Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

Discovery and systematic characterization of risk variants and genes for coronary artery disease in over a million participants.

Krishna G. Aragam, Tao Jiang, Anuj Goel, Stavroula Kanoni, Brooke N. Wolford, Elle M. Weeks, Minxian Wang, George Hindy, Wei Zhou, Christopher Grace, Carolina Roselli, Nicholas Marston, Frederick Kamanu, Ida L. Surakka, Loreto Muñoz Venegas, , Adam S. Butterworth

A coronary artery disease GWAS of 181,522 cases among 1,165,690 participants yields 241 associations (54 new); an eight-predictor consensus nominates 185 candidate causal genes, 94 with ≥3 predictors.

medRxiv · May 24, 2021 · PreprintGenetic & Genomic Medicine✦ In-depth digest

Genome-wide association study of over 40,000 bipolar disorder cases provides new insights into the underlying biology

Niamh Mullins, Andreas J. Forstner, Kevin Sean O’Connell, Brandon J. Coombes, Jonathan R. I. Coleman, Zhen Qiao, Thomas D. Als, Tim B. Bigdeli, Sigrid Børte, Julien Bryois, Alexander W. Charney, Ole Kristian Drange, Michael J. Gandal, Saskia P. Hagenaars, Masashi Ikeda, , Janos L. Kalman

Meta-analysis of 41,917 European-ancestry bipolar disorder cases versus 371,549 controls yields 64 risk loci (33 novel), neuronal and synaptic gene enrichment, and 15 eQTL-prioritized genes.

Nature Genetics · May 17, 2021Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

The Polygenic Score Catalog: an open database for reproducibility and systematic evaluation

Samuel A. Lambert, Laurent Gil, Simon Jupp, Scott C. Ritchie, Yu Xu, Annalisa Buniello, Aoife McMahon, Gad Abraham, Michael Chapman, Helen Parkinson, John Danesh, Jacqueline A. L. MacArthur, Michael Inouye

PGS Catalog standardizes 192 curated polygenic scores and metadata (86 traits); reapplied in UK Biobank, eight of nine colorectal cancer scores predicted disease in European-ancestry participants.

Nature Genetics · Mar 10, 2021Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

Improving reporting standards for polygenic scores in risk prediction studies

Hannah Wand, Samuel A. Lambert, Cecelia P. Tamburro, Michael A. Iacocca, Jack William O’Sullivan, Catherine H. Sillari, Iftikhar J. Kullo, Robb K. Rowley, Jacqueline S. Dron, Deanna Brockman, Eric Venner, Mark I. McCarthy, Antonis C. Antoniou, Douglas F. Easton, Robert Alexander Hegele, , Genevieve L. Wojcik

ClinGen and the PGS Catalog expand the GRIPS guideline into a 22-item Polygenic Risk Score Reporting Statement covering study populations, model construction, evaluation, and clinical interpretation.

Nature · Mar 10, 2021Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

LDpred2: better, faster, stronger

Florian Privé, Julyan Arbel, Bjarni Jóhann Vilhjálmsson

LDpred2 reworks LDpred with a 3 cM LD window plus sparse and auto options, reaching mean AUC 65.1% over 8 real traits versus 63.8% for lassosum.

Bioinformatics · Dec 1, 2020Peer-reviewedGenetics✦ In-depth digest

A guide to performing Polygenic Risk Score analyses

Shing Wan Choi, Timothy Shin Heng Mak, Paul F. O’Reilly

Best-practice guidance for polygenic risk score (PRS) analysis: PRS-specific quality control, shrinkage and linkage disequilibrium handling, liability-scale R^2, overfitting control, and UK Biobank power examples.

Nature Protocols · Jul 24, 2020Peer-reviewedGenomics✦ In-depth digest

Discovery of 318 novel loci for type-2 diabetes and related micro- and macrovascular outcomes among 1.4 million participants in a multi-ethnic meta-analysis.

Marijana Vujković, Jacob M. Keaton, Julie Ann Lynch, Donald R. Miller, Jin J. Zhou, Catherine Tcheandjieu, Jennifer E. Huffman, Themistocles L. Assimes, Kimberly Lorenz, Xiang Zhu, Austin T. Hilliard, Renae Judy, Jie Huang, Kyung Min Lee, Derek M. Klarin, , Saib S. Gappy

Multi-ethnic type 2 diabetes (T2D) meta-analysis of 228,499 cases and 1,178,783 controls finds 318 previously unreported loci, 804 expression-colocalized genes, and 13 SNP-by-T2D vascular-outcome interactions.

Nature Genetics · Jun 15, 2020Peer-reviewedGenetic & Genomic Medicine✦ In-depth digest

Expanding Parkinson’s disease genetics: novel risk loci, genomic context, causal insights and heritable risk

Mike A. Nalls, Cornelis Blauwendraat, Costanza Ludovica Vallerga, Karl Heilbron, Sara Bandrés‐Ciga, Diana Chang, Manuela M. X. Tan, Demis A. Kia, Alastair John Noyce, Angli Xue, José Brás, Emily Young, Rainer von Coelln, Javier Simón-Sánchez, Claudia Schulte, , Ciara García

Across 37,688 Parkinson's cases, 18,618 proxy-cases and 1.4M controls, 90 risk signals map to 78 loci (37 new); an 1805-variant polygenic score explains 26-36% of heritability.

The Lancet Neurology · Nov 6, 2019Peer-reviewedGenetics✦ In-depth digest

Genetics of 38 blood and urine biomarkers in the UK Biobank

Nasa Sinnott-Armstrong, Yosuke Tanigawa, David Amar, Nina Mars, Matthew Aguirre, Guhan Ram Venkataraman, Michael Wainberg, Hanna Maria Ollila, James P. Pirruccello, Junyang Qian, Anna Shcherbina, FinnGen, Fátima Rodríguez, Themistocles L. Assimes, Vineeta Agarwala, , Manuel A. Rivas

UK Biobank genetics of 38 blood and urine lab tests yields 1,857 independent loci; combining biomarker and disease polygenic scores improves FinnGen prediction of incident renal failure and alcoholic cirrhosis.

bioRxiv · Jun 5, 2019 · PreprintGenetics✦ In-depth digest

Current clinical use of polygenic scores will risk exacerbating health disparities

Alicia R. Martin, Masahiro Kanai, Yoichiro Kamatani, Yukinori Okada, Benjamin M. Neale, Mark J. Daly

Eurocentric GWAS make polygenic scores less accurate in non-Europeans (mean 4.9-fold lower for UK Biobank Africans); equal-sized ancestry-matched GWAS predict better in Japanese and British individuals.

Nature Genetics · Mar 29, 2019Peer-reviewedGenetics✦ In-depth digest

Genome-wide meta-analysis of depression identifies 102 independent variants and highlights the importance of the prefrontal brain regions.

David M. Howard, Mark J. Adams, Toni‐Kim Clarke, Jonathan D. Hafferty, Jude Gibson, Masoud Shirali, Jonathan R. I. Coleman, Saskia P. Hagenaars, Joey Ward, Eleanor M. Wigmore, Clara Alloza, Xueyi Shen, Miruna C. Barbu, Eileen Y. Xu, Heather Clare Whalley, , Andrew Mark McIntosh

A meta-analysis of 807,553 people from 23andMe, UK Biobank and PGC finds 102 depression variants. 87 of them replicate in 1,306,354 individuals, and heritability is enriched in prefrontal brain regions.

Nature Neuroscience · Feb 4, 2019Peer-reviewedGenetics✦ In-depth digest

Discovery Of The First Genome-Wide Significant Risk Loci For ADHD

Ditte Demontis, Raymond Kenney Walters, Joanna Martin, Manuel Mattheisen, Thomas D. Als, Esben Agerbo, Gísli Baldursson, Rich Belliveau, Jonas Bybjerg‐Grauholm, Marie Bækvad‐Hansen, Felecia E. Cerrato, Kimberly Chambert, Claire Churchhouse, Ashley Dumont, Nicholas Eriksson, , Benjamin M. Neale

Genome-wide association meta-analysis of 20,183 ADHD cases and 35,191 controls finds 12 significant loci; signal concentrates in conserved regions, constrained genes, and CNS regulatory elements.

Nature Genetics · Nov 23, 2018Peer-reviewedGenetics✦ In-depth digest

Meta-analysis of genome-wide association studies for body fat distribution in 694,649 individuals of European ancestry

Sara L. Pulit, Charli E Harlow, Andrew P. Morris, Andrew R. Wood, Craig A. Glastonbury, Jessica Tyrrell, Loïc Yengo, Teresa Cruz Ferreira, Eirini Marouli, Yingjie Ji, Jian Yang, Samuel E. Jones, Robin N. Beaumont, Damien C. Croteau‐Chonka, Thomas W. Winkler, , Cecilia M. Lindgren

Meta-analysis of waist-to-hip ratio adjusted for BMI in 694,649 European-ancestry individuals identifies 463 signals in 346 loci, roughly one-third sexually dimorphic and mostly stronger in women.

Human Molecular Genetics · Sep 12, 2018Peer-reviewedGenetics✦ In-depth digest

Genome-wide association analyses identify 44 risk variants and refine the genetic architecture of major depression

eQTLGen, Naomi R. Wray, 23andMe, Stephan Ripke, Manuel Mattheisen, Maciej Trzaskowski, Enda M. Byrne, Abdel Abdellaoui, Mark J. Adams, Esben Agerbo, Tracy Air, Till F. M. Andlauer, Silviu‐Alin Bacanu, Marie Bækvad‐Hansen, Aartjan T.F. Beekman, , Niamh Mullins

Genome-wide association meta-analysis of 130,664 major depression cases and 330,470 controls identifies 44 independent risk loci enriched in cortical neurons, conserved mammalian regions, splicing networks, and antidepressant targets.

Nature Genetics · Apr 26, 2018Peer-reviewedGenetics✦ In-depth digest

Heterogeneity in polygenic scores for common human traits

Erin Bakshis Ware, Lauren Schmitz, Jessica D. Faul, Arianna M. Gard, Colter M. Mitchell, Jennifer A. Smith, Wei Zhao, David R. Weir, Sharon LR Kardia

Polygenic scores built 434 ways in Health and Retirement Study (HRS) participants varied widely in variance explained and inter-score correlation; European-derived weights underperformed in non-Hispanic Blacks.

bioRxiv · Feb 5, 2017 · PreprintGenetics✦ In-depth digest