{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T07:33:23Z","timestamp":1793086403332,"version":"4.5.0"},"reference-count":71,"publisher":"Springer Science and Business Media LLC","license":[{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"},{"start":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T00:00:00Z","timestamp":1789516800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"DOI":"10.1038\/s41591-026-04662-6","type":"journal-article","created":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T09:02:29Z","timestamp":1789549349000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Sex-specific biological aging clocks across organs and omics"],"prefix":"10.1038","author":[{"name":"The MULTI Consortium","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-4027-3041","authenticated-orcid":false,"given":"Zhiyuan","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek","family":"Fong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-4307-9659","authenticated-orcid":false,"given":"Naowal Azraf","family":"Rahman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael R.","family":"Duggan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2706-1439","authenticated-orcid":false,"given":"Qu","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jian","family":"Zeng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunrui","family":"Zou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2640-2094","authenticated-orcid":false,"given":"Michael S.","family":"Rafii","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5443-0503","authenticated-orcid":false,"given":"Li","family":"Shen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4720-8867","authenticated-orcid":false,"given":"Paul","family":"Thompson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleanor M.","family":"Simonsick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5989-9853","authenticated-orcid":false,"given":"Keenan A.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2298-9908","authenticated-orcid":false,"given":"Andrew","family":"Zalesky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1025-8561","authenticated-orcid":false,"given":"Christos","family":"Davatzikos","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2896-5838","authenticated-orcid":false,"given":"Paul","family":"Aisen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6273-1613","authenticated-orcid":false,"given":"Luigi","family":"Ferrucci","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan M.","family":"Resnick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2077-3070","authenticated-orcid":false,"given":"Junhao","family":"Wen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,9,16]]},"reference":[{"key":"4662_CR1","doi-asserted-by":"publisher","unstructured":"Tian, Y. E. et al. Heterogeneous aging across multiple organ systems and prediction of chronic disease and mortality. Nat. Med. 29, 1221\u22121231 https:\/\/doi.org\/10.1038\/s41591-023-02296-6 (2023).","DOI":"10.1038\/s41591-023-02296-6"},{"key":"4662_CR2","doi-asserted-by":"publisher","unstructured":"Wen, J. Multiorgan biological age shows that no organ system is an island. Nat. Aging 4, 1182\u22121183 https:\/\/doi.org\/10.1038\/s43587-024-00690-4 (2024).","DOI":"10.1038\/s43587-024-00690-4"},{"key":"4662_CR3","doi-asserted-by":"publisher","first-page":"164","DOI":"10.1038\/s41586-023-06802-1","volume":"624","author":"HS-H Oh","year":"2023","unstructured":"Oh, H. S.-H. et al. Organ aging signatures in the plasma proteome track health and disease. Nature 624, 164\u2013172 (2023).","journal-title":"Nature"},{"key":"4662_CR4","doi-asserted-by":"publisher","first-page":"266","DOI":"10.1038\/s41380-018-0098-1","volume":"24","author":"JH Cole","year":"2019","unstructured":"Cole, J. H., Marioni, R. E., Harris, S. E. & Deary, I. J. Brain age and other bodily \u2018ages\u2019: implications for neuropsychiatry. Mol. Psychiatry 24, 266\u2013281 (2019).","journal-title":"Mol. Psychiatry"},{"key":"4662_CR5","doi-asserted-by":"publisher","unstructured":"Wang, K. et al. A full life cycle biological clock based on routine clinical data and its impact in health and diseases. Nat. Med. 31, 4225\u22124235 https:\/\/doi.org\/10.1038\/s41591-025-04006-w (2025).","DOI":"10.1038\/s41591-025-04006-w"},{"key":"4662_CR6","doi-asserted-by":"publisher","unstructured":"Argentieri, M. A. et al. Integrating the environmental and genetic architectures of aging and mortality. Nat. Med. 31, 1016\u22121025 https:\/\/doi.org\/10.1038\/s41591-024-03483-9 (2025).","DOI":"10.1038\/s41591-024-03483-9"},{"key":"4662_CR7","doi-asserted-by":"publisher","unstructured":"Wen, J. Refining the generation, interpretation and application of multi-organ, multi-omics biological aging clocks. Nat. Aging 5, 1897\u22121913 https:\/\/doi.org\/10.1038\/s43587-025-00928-9 (2025).","DOI":"10.1038\/s43587-025-00928-9"},{"key":"4662_CR8","doi-asserted-by":"publisher","unstructured":"MULTI Consortium et al. MRI-based multi-organ clocks for healthy aging and disease assessment. Nat. Med. 32, 82\u221292 https:\/\/doi.org\/10.1038\/s41591-025-03999-8 (2025).","DOI":"10.1038\/s41591-025-03999-8"},{"key":"4662_CR9","doi-asserted-by":"publisher","first-page":"eady8433","DOI":"10.1126\/sciadv.ady8433","volume":"11","author":"J Staerk","year":"2025","unstructured":"Staerk, J. et al. Sexual selection drives sex difference in adult life expectancy across mammals and birds. Sci. Adv. 11, eady8433 (2025).","journal-title":"Sci. Adv."},{"key":"4662_CR10","doi-asserted-by":"publisher","first-page":"844","DOI":"10.1038\/s44161-022-00131-8","volume":"1","author":"DV Zhernakova","year":"2022","unstructured":"Zhernakova, D. V. et al. Age-dependent sex differences in cardiometabolic risk factors. Nat. Cardiovasc. Res. 1, 844\u2013854 (2022).","journal-title":"Nat. Cardiovasc. Res."},{"key":"4662_CR11","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/s41582-018-0032-9","volume":"14","author":"MT Ferretti","year":"2018","unstructured":"Ferretti, M. T. et al. Sex differences in Alzheimer disease\u2014the gateway to precision medicine. Nat. Rev. Neurol. 14, 457\u2013469 (2018).","journal-title":"Nat. Rev. Neurol."},{"key":"4662_CR12","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1056\/NEJMoa2212948","volume":"388","author":"CHvan Dyck","year":"2023","unstructured":"Dyck, C. H. van et al. Lecanemab in early Alzheimer\u2019s disease. N. Engl. J. Med. 388, 9\u201321 (2023).","journal-title":"N. Engl. J. Med."},{"key":"4662_CR13","doi-asserted-by":"publisher","first-page":"1691","DOI":"10.1056\/NEJMoa2100708","volume":"384","author":"MA Mintun","year":"2021","unstructured":"Mintun, M. A. et al. Donanemab in early Alzheimer\u2019s disease. N. Engl. J. Med. 384, 1691\u20131704 (2021).","journal-title":"N. Engl. J. Med."},{"key":"4662_CR14","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-025-59964-z","volume":"16","author":"The MULTI consortium","year":"2025","unstructured":"The MULTI consortium Multi-organ metabolome biological age implicates cardiometabolic conditions and mortality risk. Nat. Commun. 16, 4871 (2025).","journal-title":"Nat. Commun."},{"key":"4662_CR15","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-46796-6","volume":"15","author":"J Wen","year":"2024","unstructured":"Wen, J. et al. The genetic architecture of multimodal human brain age. Nat. Commun. 15, 2604 (2024).","journal-title":"Nat. Commun."},{"key":"4662_CR16","doi-asserted-by":"publisher","unstructured":"The MULTI Consortium et al. Multi-organ AI endophenotypes chart the heterogeneity of pan-disease in the brain, eye, and heart. Nat. Ment. Health 4, 203\u2212230 https:\/\/doi.org\/10.1101\/2025.08.09.25333350 (2025).","DOI":"10.1101\/2025.08.09.25333350"},{"key":"4662_CR17","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1038\/s41596-022-00696-5","volume":"17","author":"S Rutherford","year":"2022","unstructured":"Rutherford, S. et al. The normative modeling framework for computational psychiatry. Nat. Protoc. 17, 1711\u20131734 (2022).","journal-title":"Nat. Protoc."},{"key":"4662_CR18","doi-asserted-by":"publisher","first-page":"137","DOI":"10.1038\/s41586-019-1657-6","volume":"575","author":"C Tannenbaum","year":"2019","unstructured":"Tannenbaum, C., Ellis, R. P., Eyssel, F., Zou, J. & Schiebinger, L. Sex and gender analysis improves science and engineering. Nature 575, 137\u2013146 (2019).","journal-title":"Nature"},{"key":"4662_CR19","doi-asserted-by":"publisher","unstructured":"Wen, J. Towards a multi-organ, multi-omics medical digital twin. Nat. Biomed. Eng. 9, 1386\u22121389 https:\/\/doi.org\/10.1038\/s41551-025-01474-w (2025).","DOI":"10.1038\/s41551-025-01474-w"},{"key":"4662_CR20","doi-asserted-by":"publisher","unstructured":"Wen, J. et al. The genetic architecture of biological age in nine human organ systems. Nat. Aging 4, 1290\u22121307 https:\/\/doi.org\/10.1038\/s43587-024-00662-8 (2024).","DOI":"10.1038\/s43587-024-00662-8"},{"key":"4662_CR21","first-page":"bbaf125","volume":"26","author":"A Boquet-Pujadas","year":"2025","unstructured":"Boquet-Pujadas, A. et al. MUTATE: a human genetic atlas of multiorgan artificial intelligence endophenotypes using genome-wide association summary statistics. Brief. Bioinform. 26, bbaf125 (2025).","journal-title":"Brief. Bioinform."},{"key":"4662_CR22","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1038\/s43587-026-01113-2","volume":"6","author":"A Zalesky","year":"2026","unstructured":"Zalesky, A., Wen, J. & Tian, Y. E. From whole-body to organ-specific biological age clocks. Nat. Aging 6, 961\u2013969 (2026).","journal-title":"Nat. Aging"},{"key":"4662_CR23","doi-asserted-by":"publisher","first-page":"201","DOI":"10.1212\/WNL.0b013e3181cb3e25","volume":"74","author":"RC Petersen","year":"2010","unstructured":"Petersen, R. C. et al. Alzheimer\u2019s Disease Neuroimaging Initiative (ADNI): clinical characterization. Neurology 74, 201\u2013209 (2010).","journal-title":"Neurology"},{"key":"4662_CR24","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1056\/NEJMoa2305032","volume":"389","author":"RA Sperling","year":"2023","unstructured":"Sperling, R. A. et al. Trial of solanezumab in preclinical Alzheimer\u2019s disease. N. Engl. J. Med. 389, 1096\u20131107 (2023).","journal-title":"N. Engl. J. Med."},{"key":"4662_CR25","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1001\/jamaneurol.2020.0387","volume":"77","author":"RA Sperling","year":"2020","unstructured":"Sperling, R. A. et al. Association of factors with elevated amyloid burden in clinically normal older individuals. JAMA Neurol. 77, 735\u2013745 (2020).","journal-title":"JAMA Neurol."},{"key":"4662_CR26","doi-asserted-by":"publisher","first-page":"102229","DOI":"10.1016\/j.nicl.2020.102229","volume":"26","author":"A-MG de Lange","year":"2020","unstructured":"de Lange, A.-M. G. & Cole, J. H. Commentary: Correction procedures in brain-age prediction. Neuroimage Clin. 26, 102229 (2020).","journal-title":"Neuroimage Clin."},{"key":"4662_CR27","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1038\/ng.3211","volume":"47","author":"BK Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan, B. K. et al. LD Score regression distinguishes confounding from polygenicity in genome-wide association studies. Nat. Genet. 47, 291\u2013295 (2015).","journal-title":"Nat. Genet."},{"key":"4662_CR28","doi-asserted-by":"publisher","unstructured":"The MULTI Consortium et al. Sleep chart of biological ageing clocks in middle and late life. Nature https:\/\/doi.org\/10.1038\/s41586-026-10524-5 (2026).","DOI":"10.1038\/s41586-026-10524-5"},{"key":"4662_CR29","doi-asserted-by":"publisher","unstructured":"Wen, J. Too little or too much sleep is linked to faster ageing throughout the body. Nature https:\/\/doi.org\/10.1038\/d41586-026-01564-y (2026).","DOI":"10.1038\/d41586-026-01564-y"},{"key":"4662_CR30","doi-asserted-by":"publisher","first-page":"535","DOI":"10.1038\/nn.2303","volume":"12","author":"N Kriegeskorte","year":"2009","unstructured":"Kriegeskorte, N., Simmons, W. K., Bellgowan, P. S. F. & Baker, C. I. Circular analysis in systems neuroscience: the dangers of double dipping. Nat. Neurosci. 12, 535\u2013540 (2009).","journal-title":"Nat. Neurosci."},{"key":"4662_CR31","doi-asserted-by":"publisher","first-page":"45","DOI":"10.1161\/ATVBAHA.119.313154","volume":"40","author":"HS Lumish","year":"2020","unstructured":"Lumish, H. S., O\u2019Reilly, M. & Reilly, M. P. Sex differences in genomic drivers of adipose distribution and related cardiometabolic disorders. Arter. Thromb. Vasc. Biol. 40, 45\u201360 (2020).","journal-title":"Arter. Thromb. Vasc. Biol."},{"key":"4662_CR32","doi-asserted-by":"publisher","unstructured":"Matz-Soja, M., Berg, T. & Kietzmann, T. Sex-related variations in liver homeostasis and disease: from zonation dynamics to clinical implications. J. Hepatol. 84, 181\u2013193 https:\/\/doi.org\/10.1016\/j.jhep.2025.08.007 (2025).","DOI":"10.1016\/j.jhep.2025.08.007"},{"key":"4662_CR33","doi-asserted-by":"publisher","first-page":"240","DOI":"10.1016\/j.cmet.2024.01.002","volume":"36","author":"AR Nichols","year":"2024","unstructured":"Nichols, A. R., Chavarro, J. E. & Oken, E. Reproductive risk factors across the female lifecourse and later metabolic health. Cell Metab. 36, 240\u2013262 (2024).","journal-title":"Cell Metab."},{"key":"4662_CR34","doi-asserted-by":"publisher","first-page":"191","DOI":"10.1016\/j.jhep.2022.01.016","volume":"77","author":"D Marti-Aguado","year":"2022","unstructured":"Marti-Aguado, D., Clemente-Sanchez, A. & Bataller, R. Cigarette smoking and liver diseases. J. Hepatol. 77, 191\u2013205 (2022).","journal-title":"J. Hepatol."},{"key":"4662_CR35","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-12348-6","volume":"10","author":"ST Gal-Oz","year":"2019","unstructured":"Gal-Oz, S. T. et al. ImmGen report: sexual dimorphism in the immune system transcriptome. Nat. Commun. 10, 4295 (2019).","journal-title":"Nat. Commun."},{"key":"4662_CR36","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1111\/eva.13167","volume":"14","author":"VL Kronzer","year":"2020","unstructured":"Kronzer, V. L., Bridges, S. L. & Davis, J. M. Why women have more autoimmune diseases than men: an evolutionary perspective. Evol. Appl. 14, 629\u2013633 (2020).","journal-title":"Evol. Appl."},{"key":"4662_CR37","doi-asserted-by":"publisher","first-page":"13","DOI":"10.1007\/s40142-019-0157-1","volume":"7","author":"L Dumitrescu","year":"2019","unstructured":"Dumitrescu, L., Mayeda, E. R., Sharman, K., Moore, A. M. & Hohman, T. J. Sex differences in the genetic architecture of Alzheimer\u2019s disease. Curr. Genet. Med. Rep. 7, 13\u201321 (2019).","journal-title":"Curr. Genet. Med. Rep."},{"key":"4662_CR38","doi-asserted-by":"publisher","first-page":"303","DOI":"10.1001\/jamapsychiatry.2019.4079","volume":"77","author":"KJS Lewis","year":"2020","unstructured":"Lewis, K. J. S. et al. Comparison of genetic liability for sleep traits among individuals with bipolar disorder I or II and control participants. JAMA Psychiatry 77, 303\u2013310 (2020).","journal-title":"JAMA Psychiatry"},{"key":"4662_CR39","doi-asserted-by":"publisher","first-page":"e12660","DOI":"10.1111\/gbb.12660","volume":"19","author":"AK Merikangas","year":"2020","unstructured":"Merikangas, A. K. & Almasy, L. Using the tools of genetic epidemiology to understand sex differences in neuropsychiatric disorders. Genes Brain Behav. 19, e12660 (2020).","journal-title":"Genes Brain Behav."},{"key":"4662_CR40","doi-asserted-by":"publisher","first-page":"e85082","DOI":"10.7554\/eLife.85082","volume":"12","author":"S Rutherford","year":"2023","unstructured":"Rutherford, S. et al. Evidence for embracing normative modeling. Elife 12, e85082 (2023).","journal-title":"Elife"},{"key":"4662_CR41","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1007\/s11892-018-1031-3","volume":"18","author":"E Chang","year":"2018","unstructured":"Chang, E., Varghese, M. & Singer, K. Gender and sex differences in adipose tissue. Curr. Diab. Rep. 18, 69 (2018).","journal-title":"Curr. Diab. Rep."},{"key":"4662_CR42","doi-asserted-by":"publisher","unstructured":"Smith, S. M., Miller, K. L. & Nichols, T. E. Characterising ongoing brain aging and baseline effects from cross-sectional data. Imaging Neurosci. (Camb.) 3, IMAG.a.39 https:\/\/doi.org\/10.1162\/IMAG.a.39 (2025).","DOI":"10.1162\/IMAG.a.39"},{"key":"4662_CR43","doi-asserted-by":"publisher","unstructured":"Wu, Q., McIlvain, G., Yu, Z. & Wen, J. Pan-FM: a pan-organ foundation model with saliency-guided masking for missing robustness. Preprint at https:\/\/doi.org\/10.48550\/arXiv.2605.07055 (2026).","DOI":"10.48550\/arXiv.2605.07055"},{"key":"4662_CR44","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41586-018-0579-z","volume":"562","author":"C Bycroft","year":"2018","unstructured":"Bycroft, C. et al. The UK Biobank resource with deep phenotyping and genomic data. Nature 562, 203\u2013209 (2018).","journal-title":"Nature"},{"key":"4662_CR45","doi-asserted-by":"crossref","unstructured":"Shock, N. W. et al. Normal human aging: the Baltimore Longitudinal Study of Aging. J. Gerontol. 40, 767 (1985).","DOI":"10.1093\/geronj\/40.6.767"},{"key":"4662_CR46","doi-asserted-by":"publisher","unstructured":"Duggan, M. R. et al. Proteomic analyses reveal plasma EFEMP1 and CXCL12 as biomarkers and determinants of neurodegeneration. Alzheimers Dement. 20, 6486\u20136505 https:\/\/doi.org\/10.1002\/alz.14142 (2024).","DOI":"10.1002\/alz.14142"},{"key":"4662_CR47","doi-asserted-by":"publisher","first-page":"508","DOI":"10.1038\/s41586-022-05473-8","volume":"613","author":"MI Kurki","year":"2023","unstructured":"Kurki, M. I. et al. FinnGen provides genetic insights from a well-phenotyped isolated population. Nature 613, 508\u2013518 (2023).","journal-title":"Nature"},{"key":"4662_CR48","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1038\/s41588-021-00870-7","volume":"53","author":"J Mbatchou","year":"2021","unstructured":"Mbatchou, J. et al. Computationally efficient whole-genome regression for quantitative and binary traits. Nat. Genet. 53, 1097\u20131103 (2021).","journal-title":"Nat. Genet."},{"key":"4662_CR49","doi-asserted-by":"publisher","first-page":"291","DOI":"10.1002\/wps.20270","volume":"14","author":"MC O\u2019Donovan","year":"2015","unstructured":"O\u2019Donovan, M. C. What have we learned from the Psychiatric Genomics Consortium. World Psychiatry 14, 291\u2013293 (2015).","journal-title":"World Psychiatry"},{"key":"4662_CR50","doi-asserted-by":"publisher","first-page":"101694","DOI":"10.1016\/j.media.2020.101694","volume":"63","author":"J Wen","year":"2020","unstructured":"Wen, J. et al. Convolutional neural networks for classification of Alzheimer\u2019s disease: overview and reproducible evaluation. Med. Image Anal. 63, 101694 (2020).","journal-title":"Med. Image Anal."},{"key":"4662_CR51","doi-asserted-by":"publisher","first-page":"2867","DOI":"10.1093\/bioinformatics\/btq559","volume":"26","author":"A Manichaikul","year":"2010","unstructured":"Manichaikul, A. et al. Robust relationship inference in genome-wide association studies. Bioinformatics 26, 2867\u20132873 (2010).","journal-title":"Bioinformatics"},{"key":"4662_CR52","doi-asserted-by":"publisher","first-page":"459","DOI":"10.1038\/nrg2813","volume":"11","author":"AL Price","year":"2010","unstructured":"Price, A. L., Zaitlen, N. A., Reich, D. & Patterson, N. New approaches to population stratification in genome-wide association studies. Nat. Rev. Genet. 11, 459\u2013463 (2010).","journal-title":"Nat. Rev. Genet."},{"key":"4662_CR53","doi-asserted-by":"publisher","first-page":"2776","DOI":"10.1093\/bioinformatics\/btx299","volume":"33","author":"G Abraham","year":"2017","unstructured":"Abraham, G., Qiu, Y. & Inouye, M. FlashPCA2: principal component analysis of Biobank-scale genotype datasets. Bioinformatics 33, 2776\u20132778 (2017).","journal-title":"Bioinformatics"},{"key":"4662_CR54","doi-asserted-by":"publisher","first-page":"e2300842120","DOI":"10.1073\/pnas.2300842120","volume":"120","author":"J Wen","year":"2023","unstructured":"Wen, J. et al. Genomic loci influence patterns of structural covariance in the human brain. Proc. Natl Acad. Sci. USA 120, e2300842120 (2023).","journal-title":"Proc. Natl Acad. Sci. USA"},{"key":"4662_CR55","doi-asserted-by":"publisher","unstructured":"Wen, J. et al. Characterizing heterogeneity in neuroimaging, cognition, clinical symptoms, and genetics among patients with late-life depression. JAMA Psychiatry 79, 464\u2013474 https:\/\/doi.org\/10.1001\/jamapsychiatry.2022.0020 (2022).","DOI":"10.1001\/jamapsychiatry.2022.0020"},{"key":"4662_CR56","doi-asserted-by":"publisher","first-page":"420","DOI":"10.1038\/s41398-024-03121-5","volume":"14","author":"J Wen","year":"2024","unstructured":"Wen, J. et al. Genetic and clinical correlates of two neuroanatomical AI dimensions in the Alzheimer\u2019s disease continuum. Transl. Psychiatry 14, 420 (2024).","journal-title":"Transl. Psychiatry"},{"key":"4662_CR57","doi-asserted-by":"publisher","first-page":"1749","DOI":"10.1038\/s41588-019-0530-8","volume":"51","author":"L Jiang","year":"2019","unstructured":"Jiang, L. et al. A resource-efficient tool for mixed model association analysis of large-scale data. Nat. Genet. 51, 1749\u20131755 (2019).","journal-title":"Nat. Genet."},{"key":"4662_CR58","doi-asserted-by":"publisher","first-page":"76","DOI":"10.1016\/j.ajhg.2010.11.011","volume":"88","author":"J Yang","year":"2011","unstructured":"Yang, J., Lee, S. H., Goddard, M. E. & Visscher, P. M. GCTA: a tool for genome-wide complex trait analysis. Am. J. Hum. Genet. 88, 76\u201382 (2011).","journal-title":"Am. J. Hum. Genet."},{"key":"4662_CR59","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-017-01261-5","volume":"8","author":"K Watanabe","year":"2017","unstructured":"Watanabe, K., Taskesen, E., van Bochoven, A. & Posthuma, D. Functional mapping and annotation of genetic associations with FUMA. Nat. Commun. 8, 1826 (2017).","journal-title":"Nat. Commun."},{"key":"4662_CR60","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-021-21446-3","volume":"12","author":"J Zeng","year":"2021","unstructured":"Zeng, J. et al. Widespread signatures of natural selection across human complex traits and functional genomic categories. Nat. Commun. 12, 1164 (2021).","journal-title":"Nat. Commun."},{"key":"4662_CR61","doi-asserted-by":"publisher","first-page":"746","DOI":"10.1038\/s41588-018-0101-4","volume":"50","author":"J Zeng","year":"2018","unstructured":"Zeng, J. et al. Signatures of negative selection in the genetic architecture of human complex traits. Nat. Genet. 50, 746\u2013753 (2018).","journal-title":"Nat. Genet."},{"key":"4662_CR62","doi-asserted-by":"publisher","first-page":"e34408","DOI":"10.7554\/eLife.34408","volume":"7","author":"G Hemani","year":"2018","unstructured":"Hemani, G. et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife 7, e34408 (2018).","journal-title":"Elife"},{"key":"4662_CR63","doi-asserted-by":"publisher","first-page":"1614","DOI":"10.1001\/jama.2021.18236","volume":"326","author":"VW Skrivankova","year":"2021","unstructured":"Skrivankova, V. W. et al. Strengthening the Reporting of Observational Studies in Epidemiology Using Mendelian Randomization: the STROBE-MR statement. JAMA 326, 1614\u20131621 (2021).","journal-title":"JAMA"},{"key":"4662_CR64","doi-asserted-by":"publisher","first-page":"6","DOI":"10.1038\/s43586-021-00092-5","volume":"2","author":"E Sanderson","year":"2022","unstructured":"Sanderson, E. et al. Mendelian randomization. Nat. Rev. Methods Primers 2, 6 (2022).","journal-title":"Nat. Rev. Methods Primers"},{"key":"4662_CR65","doi-asserted-by":"publisher","first-page":"1783","DOI":"10.1002\/sim.7221","volume":"36","author":"J Bowden","year":"2017","unstructured":"Bowden, J. et al. A framework for the investigation of pleiotropy in two-sample summary data Mendelian randomization. Stat. Med. 36, 1783\u20131802 (2017).","journal-title":"Stat. Med."},{"key":"4662_CR66","doi-asserted-by":"publisher","first-page":"1236","DOI":"10.1038\/ng.3406","volume":"47","author":"B Bulik-Sullivan","year":"2015","unstructured":"Bulik-Sullivan, B. et al. An atlas of genetic correlations across human diseases and traits. Nat. Genet. 47, 1236\u20131241 (2015).","journal-title":"Nat. Genet."},{"key":"4662_CR67","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1038\/s41588-023-01575-9","volume":"55","author":"WUK Li","year":"2023","unstructured":"Li, W. U. K. Biobank pharma proteomics resource. Nat. Genet. 55, 1781 (2023).","journal-title":"Nat. Genet."},{"key":"4662_CR68","doi-asserted-by":"publisher","first-page":"329","DOI":"10.1038\/s41586-023-06592-6","volume":"622","author":"BB Sun","year":"2023","unstructured":"Sun, B. B. et al. Plasma proteomic associations with genetics and health in the UK Biobank. Nature 622, 329\u2013338 (2023).","journal-title":"Nature"},{"key":"4662_CR69","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1093\/aje\/kwx016","volume":"186","author":"P W\u00fcrtz","year":"2017","unstructured":"W\u00fcrtz, P. et al. Quantitative serum nuclear magnetic resonance metabolomics in large-scale epidemiology: a primer on -omic technologies. Am. J. Epidemiol. 186, 1084\u20131096 (2017).","journal-title":"Am. J. Epidemiol."},{"key":"4662_CR70","doi-asserted-by":"publisher","DOI":"10.1038\/s41597-023-01949-y","volume":"10","author":"SC Ritchie","year":"2023","unstructured":"Ritchie, S. C. et al. Quality control and removal of technical variation of NMR metabolic biomarker data in ~120,000 UK Biobank participants. Sci. Data 10, 64 (2023).","journal-title":"Sci. Data"},{"key":"4662_CR71","unstructured":"Wen, J. MLNI (version 0.1.4). GitHub https:\/\/github.com\/anbai106\/mlni (2025)."}],"updated-by":[{"DOI":"10.1038\/s41591-026-04776-x","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T00:00:00Z","timestamp":1792972800000}}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04662-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04662-6","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04662-6.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T06:39:48Z","timestamp":1793083188000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-026-04662-6"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,16]]},"references-count":71,"alternative-id":["4662"],"URL":"https:\/\/doi.org\/10.1038\/s41591-026-04662-6","relation":{},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,16]]},"assertion":[{"value":"4 April 2026","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"18 August 2026","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 September 2026","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"26 October 2026","order":5,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":6,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"A Correction to this paper has been published:","order":7,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"https:\/\/doi.org\/10.1038\/s41591-026-04776-x","URL":"https:\/\/doi.org\/10.1038\/s41591-026-04776-x","order":8,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing interests.","order":1,"name":"Ethics","label":"Competing interests","group":{"name":"EthicsHeading","label":"Ethics"}}]}}