{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T00:53:57Z","timestamp":1792457637633,"version":"4.5.0"},"reference-count":89,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T00:00:00Z","timestamp":1716854400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Transl Psychiatry"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Previous observational investigations suggest that structural and diffusion imaging-derived phenotypes (IDPs) are associated with major neurodegenerative diseases; however, whether these associations are causal remains largely uncertain. Herein we conducted bidirectional two-sample Mendelian randomization analyses to infer the causal relationships between structural and diffusion IDPs and major neurodegenerative diseases using common genetic variants-single nucleotide polymorphism (SNPs) as instrumental variables. Summary statistics of genome-wide association study (GWAS) for structural and diffusion IDPs were obtained from 33,224 individuals in the UK Biobank cohort. Summary statistics of GWAS for seven major neurodegenerative diseases were obtained from the largest GWAS for each disease to date. The forward MR analyses identified significant or suggestively statistical causal effects of genetically predicted three structural IDPs on Alzheimer\u2019s disease (AD), frontotemporal dementia (FTD), and multiple sclerosis. For example, the reduction in the surface area of the left superior temporal gyrus was associated with a higher risk of AD. The reverse MR analyses identified significantly or suggestively statistical causal effects of genetically predicted AD, Lewy body dementia (LBD), and FTD on nine structural and diffusion IDPs. For example, LBD was associated with increased mean diffusivity in the right superior longitudinal fasciculus and AD was associated with decreased gray matter volume in the right ventral striatum. Our findings might contribute to shedding light on the prediction and therapeutic intervention for the major neurodegenerative diseases at the neuroimaging level.<\/jats:p>","DOI":"10.1038\/s41398-024-02939-3","type":"journal-article","created":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T04:02:25Z","timestamp":1716868945000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["Bidirectional two-sample Mendelian randomization analyses support causal relationships between structural and diffusion imaging-derived phenotypes and the risk of major neurodegenerative diseases"],"prefix":"10.1038","volume":"14","author":[{"given":"Zirui","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuan","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haonan","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixuan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yaoyi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingyu","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yayuan","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4744-5616","authenticated-orcid":false,"given":"Qiang","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9473-1047","authenticated-orcid":false,"given":"Jiayuan","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0569-3873","authenticated-orcid":false,"given":"Zengguang","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3715-165X","authenticated-orcid":false,"given":"Junping","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,5,28]]},"reference":[{"key":"2939_CR1","doi-asserted-by":"crossref","unstructured":"Nichols E, Szoeke CEI, Vollset SE, Abbasi N, Abd-Allah F, Abdela J, et al. Global, regional, and national burden of Alzheimer\u2019s disease and other dementias, 1990\u20132016: a systematic analysis for the Global Burden of Disease Study 2016. The Lancet Neurology. 2019;18:88\u2013106.","DOI":"10.1016\/S1474-4422(18)30403-4"},{"key":"2939_CR2","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1016\/S0140-6736(20)30925-9","volume":"396","author":"T Vos","year":"2020","unstructured":"Vos T, Lim SS, Abbafati C, Abbas KM, Abbasi M, Abbasifard M, et al. Global burden of 369 diseases and injuries in 204 countries and territories, 1990\u20132019: a systematic analysis for the Global Burden of Disease Study 2019. Lancet. 2020;396:1204\u201322.","journal-title":"Lancet"},{"key":"2939_CR3","doi-asserted-by":"publisher","first-page":"700","DOI":"10.1002\/alz.12638","volume":"18","author":"J Gaugler","year":"2022","unstructured":"Gaugler J, James B, Johnson T, Reimer J, Solis M, Weuve J, et al. 2022 Alzheimer\u2019s disease facts and figures. Alzheimers Dement. 2022;18:700\u201389.","journal-title":"Alzheimers Dement"},{"key":"2939_CR4","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1016\/S1474-4422(21)00030-2","volume":"20","author":"E Tolosa","year":"2021","unstructured":"Tolosa E, Garrido A, Scholz SW, Poewe W. Challenges in the diagnosis of Parkinson\u2019s disease. Lancet Neurol. 2021;20:385\u201397.","journal-title":"Lancet Neurol"},{"key":"2939_CR5","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1016\/S0140-6736(22)01272-7","volume":"400","author":"EL Feldman","year":"2022","unstructured":"Feldman EL, Goutman SA, Petri S, Mazzini L, Savelieff MG, Shaw PJ, et al. Amyotrophic lateral sclerosis. Lancet. 2022;400:1363\u201380.","journal-title":"Lancet"},{"key":"2939_CR6","doi-asserted-by":"publisher","first-page":"157","DOI":"10.1016\/S1474-4422(19)30153-X","volume":"19","author":"JP Taylor","year":"2020","unstructured":"Taylor JP, McKeith IG, Burn DJ, Boeve BF, Weintraub D, Bamford C, et al. New evidence on the management of Lewy body dementia. Lancet Neurol. 2020;19:157\u201369.","journal-title":"Lancet Neurol"},{"key":"2939_CR7","doi-asserted-by":"publisher","first-page":"258","DOI":"10.1016\/S1474-4422(21)00341-0","volume":"21","author":"BF Boeve","year":"2022","unstructured":"Boeve BF, Boxer AL, Kumfor F, Pijnenburg Y, Rohrer JD. Advances and controversies in frontotemporal dementia: diagnosis, biomarkers, and therapeutic considerations. Lancet Neurol. 2022;21:258\u201372.","journal-title":"Lancet Neurol"},{"key":"2939_CR8","doi-asserted-by":"crossref","unstructured":"Walker FO. Huntington\u2019s disease. The Lancet. 2007;369:218\u201328.","DOI":"10.1016\/S0140-6736(07)60111-1"},{"key":"2939_CR9","doi-asserted-by":"publisher","first-page":"1293","DOI":"10.1007\/s00415-018-9016-3","volume":"266","author":"A Chandra","year":"2019","unstructured":"Chandra A, Dervenoulas G, Politis M. Magnetic resonance imaging in Alzheimer\u2019s disease and mild cognitive impairment. J. Neurol. 2019;266:1293\u2013302.","journal-title":"J. Neurol"},{"key":"2939_CR10","doi-asserted-by":"crossref","unstructured":"Yousaf T, Dervenoulas G, Valkimadi P-E, Politis M. Neuroimaging in Lewy body dementia. J Neurol. 2019;266:1\u201326.","DOI":"10.1007\/s00415-018-8892-x"},{"key":"2939_CR11","doi-asserted-by":"publisher","first-page":"3144","DOI":"10.1007\/s00415-020-09863-8","volume":"268","author":"E Sarasso","year":"2021","unstructured":"Sarasso E, Agosta F, Piramide N, Filippi M. Progression of grey and white matter brain damage in Parkinson\u2019s disease: a critical review of structural MRI literature. J. Neurol. 2021;268:3144\u201379.","journal-title":"J. Neurol"},{"key":"2939_CR12","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1111\/ene.14648","volume":"28","author":"B Tan","year":"2021","unstructured":"Tan B, Shishegar R, Poudel GR, Fornito A, Georgiou-Karistianis N. Cortical morphometry and neural dysfunction in Huntington\u2019s disease: a review. Eur. J. Neurol. 2021;28:1406\u201319.","journal-title":"Eur. J. Neurol"},{"key":"2939_CR13","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1016\/j.neubiorev.2013.03.006","volume":"37","author":"J Lansley","year":"2013","unstructured":"Lansley J, Mataix-Cols D, Grau M, Radua J, Sastre-Garriga J. Localized grey matter atrophy in multiple sclerosis: a meta-analysis of voxel-based morphometry studies and associations with functional disability. Neurosci. Biobehav. Rev. 2013;37:819\u201330.","journal-title":"Neurosci. Biobehav. Rev"},{"key":"2939_CR14","doi-asserted-by":"crossref","unstructured":"Pengo M, Premi E, Borroni B. Dissecting the Many Faces of Frontotemporal Dementia: An Imaging Perspective. Int. J. Mol. Sci. 2022;23:12867.","DOI":"10.3390\/ijms232112867"},{"key":"2939_CR15","doi-asserted-by":"publisher","first-page":"316","DOI":"10.1016\/j.nurt.2007.05.011","volume":"4","author":"AL Alexander","year":"2007","unstructured":"Alexander AL, Lee JE, Lazar M, Field AS. Diffusion tensor imaging of the brain. Neurotherapeutics. 2007;4:316\u201329.","journal-title":"Neurotherapeutics"},{"key":"2939_CR16","doi-asserted-by":"publisher","first-page":"906","DOI":"10.1212\/WNL.0b013e318266fc51","volume":"79","author":"R Watson","year":"2012","unstructured":"Watson R, Blamire AM, Colloby SJ, Wood JS, Barber R, He J, et al. Characterizing dementia with Lewy bodies by means of diffusion tensor imaging. Neurology. 2012;79:906\u201314.","journal-title":"Neurology"},{"key":"2939_CR17","doi-asserted-by":"publisher","first-page":"e943","DOI":"10.1212\/WNL.0000000000010235","volume":"95","author":"S Kalra","year":"2020","unstructured":"Kalra S, M\u00fcller H-P, Ishaque A, Zinman L, Korngut L, Genge A, et al. A prospective harmonized multicenter DTI study of cerebral white matter degeneration in ALS. Neurology. 2020;95:e943\u2013e52.","journal-title":"Neurology"},{"key":"2939_CR18","doi-asserted-by":"publisher","first-page":"1133","DOI":"10.1002\/sim.3034","volume":"27","author":"DA Lawlor","year":"2008","unstructured":"Lawlor DA, Harbord RM, Sterne JAC, Timpson N, Davey Smith G. Mendelian randomization: using genes as instruments for making causal inferences in epidemiology. Stat. Med. 2008;27:1133\u201363.","journal-title":"Stat. Med"},{"key":"2939_CR19","doi-asserted-by":"publisher","first-page":"3253","DOI":"10.1681\/ASN.2016010098","volume":"27","author":"P Sekula","year":"2016","unstructured":"Sekula P, Del Greco MF, Pattaro C, Kottgen A. Mendelian randomization as an approach to assess causality using observational data. J. Am. Soc. Nephrol. 2016;27:3253\u201365.","journal-title":"J. Am. Soc. Nephrol"},{"key":"2939_CR20","doi-asserted-by":"publisher","first-page":"414","DOI":"10.1038\/s41588-019-0358-2","volume":"51","author":"BW Kunkle","year":"2019","unstructured":"Kunkle BW, Grenier-Boley B, Sims R, Bis JC, Damotte V, Naj AC, et al. Genetic meta-analysis of diagnosed Alzheimer\u2019s disease identifies new risk loci and implicates A\u03b2, tau, immunity and lipid processing. Nat. Genet. 2019;51:414\u201330.","journal-title":"Nat. Genet"},{"key":"2939_CR21","doi-asserted-by":"publisher","first-page":"1091","DOI":"10.1016\/S1474-4422(19)30320-5","volume":"18","author":"MA Nalls","year":"2019","unstructured":"Nalls MA, Blauwendraat C, Vallerga CL, Heilbron K, Bandres-Ciga S, Chang D, et al. Identification of novel risk loci, causal insights, and heritable risk for Parkinson\u2019s disease: a meta-analysis of genome-wide association studies. Lancet Neurol. 2019;18:1091\u2013102.","journal-title":"Lancet Neurol"},{"key":"2939_CR22","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1016\/S1474-4422(14)70065-1","volume":"13","author":"R Ferrari","year":"2014","unstructured":"Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JBJ, et al. Frontotemporal dementia and its subtypes: a genome-wide association study. Lancet Neurol. 2014;13:686\u201399.","journal-title":"Lancet Neurol"},{"key":"2939_CR23","doi-asserted-by":"publisher","first-page":"210","DOI":"10.1038\/s41586-018-0571-7","volume":"562","author":"LT Elliott","year":"2018","unstructured":"Elliott LT, Sharp K, Alfaro-Almagro F, Shi S, Miller KL, Douaud G, et al. Genome-wide association studies of brain imaging phenotypes in UK Biobank. Nature. 2018;562:210\u201316.","journal-title":"Nature"},{"key":"2939_CR24","doi-asserted-by":"publisher","first-page":"737","DOI":"10.1038\/s41593-021-00826-4","volume":"24","author":"SM Smith","year":"2021","unstructured":"Smith SM, Douaud G, Chen W, Hanayik T, Alfaro-Almagro F, Sharp K, et al. An expanded set of genome-wide association studies of brain imaging phenotypes in UK Biobank. Nat. Neurosci. 2021;24:737\u201345.","journal-title":"Nat. Neurosci"},{"key":"2939_CR25","doi-asserted-by":"publisher","DOI":"10.1186\/s12864-021-07661-8","volume":"22","author":"W Song","year":"2021","unstructured":"Song W, Qian W, Wang W, Yu S, Lin GN. Mendelian randomization studies of brain MRI yield insights into the pathogenesis of neuropsychiatric disorders. BMC Genomics. 2021;22:342.","journal-title":"BMC Genomics"},{"key":"2939_CR26","doi-asserted-by":"publisher","DOI":"10.1038\/s41398-021-01599-x","volume":"11","author":"B-S Wu","year":"2021","unstructured":"Wu B-S, Zhang Y-R, Li H-Q, Kuo K, Chen S-D, Dong Q, et al. Cortical structure and the risk for Alzheimer\u2019s disease: a bidirectional Mendelian randomization study. Transl. Psychiatry. 2021;11:476.","journal-title":"Transl. Psychiatry"},{"key":"2939_CR27","doi-asserted-by":"publisher","first-page":"881","DOI":"10.1007\/s40120-022-00353-9","volume":"11","author":"Y Li","year":"2022","unstructured":"Li Y, Zheng J, Li T, Zhang J. White matter and Alzheimer\u2019s disease: A bidirectional Mendelian randomization study. Neurol. Ther. 2022;11:881\u201392.","journal-title":"Neurol. Ther"},{"key":"2939_CR28","doi-asserted-by":"publisher","first-page":"2059","DOI":"10.1093\/brain\/awac392","volume":"146","author":"A Seyedsalehi","year":"2023","unstructured":"Seyedsalehi A, Warrier V, Bethlehem RAI, Perry BI, Burgess S, Murray GK. Educational attainment, structural brain reserve and Alzheimer\u2019s disease: a Mendelian randomization analysis. Brain. 2023;146:2059\u201374.","journal-title":"Brain"},{"key":"2939_CR29","doi-asserted-by":"publisher","first-page":"1523","DOI":"10.1038\/nn.4393","volume":"19","author":"KL Miller","year":"2016","unstructured":"Miller KL, Alfaro-Almagro F, Bangerter NK, Thomas DL, Yacoub E, Xu J, et al. Multimodal population brain imaging in the UK Biobank prospective epidemiological study. Nat. Neurosci. 2016;19:1523\u201336.","journal-title":"Nat. Neurosci"},{"key":"2939_CR30","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1038\/s41588-021-00973-1","volume":"53","author":"W van Rheenen","year":"2021","unstructured":"van Rheenen W, van der Spek RAA, Bakker MK, van Vugt JJFA, Hop PJ, Zwamborn RAJ, et al. Common and rare variant association analyses in amyotrophic lateral sclerosis identify 15 risk loci with distinct genetic architectures and neuron-specific biology. Nat. Genet. 2021;53:1636\u201348.","journal-title":"Nat. Genet"},{"key":"2939_CR31","unstructured":"International Multiple Sclerosis Genetics C, Patsopoulos NA, Baranzini SE, Santaniello A, Shoostari P, Cotsapas C, et al. Multiple sclerosis genomic map implicates peripheral immune cells and microglia in susceptibility. Science. 2019;365:eaav7188."},{"key":"2939_CR32","doi-asserted-by":"publisher","first-page":"294","DOI":"10.1038\/s41588-021-00785-3","volume":"53","author":"R Chia","year":"2021","unstructured":"Chia R, Sabir MS, Bandres-Ciga S, Saez-Atienzar S, Reynolds RH, Gustavsson E, et al. Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nat. Genet. 2021;53:294\u2013303.","journal-title":"Nat. Genet"},{"key":"2939_CR33","doi-asserted-by":"crossref","unstructured":"Lee J-M, Correia K, Loupe J, Kim K-H, Barker D, Hong EP, et al. CAG Repeat Not Polyglutamine Length Determines Timing of Huntington\u2019s Disease Onset. Cell. 2019;178:887\u2013900.e14.","DOI":"10.1016\/j.cell.2019.06.036"},{"key":"2939_CR34","doi-asserted-by":"publisher","first-page":"1276","DOI":"10.1038\/s41588-021-00921-z","volume":"53","author":"DP Wightman","year":"2021","unstructured":"Wightman DP, Jansen IE, Savage JE, Shadrin AA, Bahrami S, Holland D, et al. A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer\u2019s disease. Nat. Genet. 2021;53:1276\u201382.","journal-title":"Nat. Genet"},{"key":"2939_CR35","doi-asserted-by":"publisher","first-page":"412","DOI":"10.1038\/s41588-022-01024-z","volume":"54","author":"C Bellenguez","year":"2022","unstructured":"Bellenguez C, K\u00fc\u00e7\u00fckali F, Jansen IE, Kleineidam L, Moreno-Grau S, Amin N, et al. New insights into the genetic etiology of Alzheimer\u2019s disease and related dementias. Nat. Genet. 2022;54:412\u201336.","journal-title":"Nat. Genet"},{"key":"2939_CR36","doi-asserted-by":"publisher","first-page":"fcac125","DOI":"10.1093\/braincomms\/fcac125","volume":"4","author":"V Escott-Price","year":"2022","unstructured":"Escott-Price V, Hardy J. Genome-wide association studies for Alzheimer\u2019s disease: bigger is not always better. Brain Commun. 2022;4:fcac125.","journal-title":"Brain Commun"},{"key":"2939_CR37","doi-asserted-by":"crossref","unstructured":"Wu Y, Sun Z, Zheng Q, Miao J, Dorn S, Mukherjee S, et al. Pervasive biases in proxy GWAS based on parental history of Alzheimer\u2019s disease. bioRxiv. 2023:2023.10.13.562272.","DOI":"10.1101\/2023.10.13.562272"},{"key":"2939_CR38","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1002\/gepi.21998","volume":"40","author":"S Burgess","year":"2016","unstructured":"Burgess S, Davies NM, Thompson SG. Bias due to participant overlap in two-sample Mendelian randomization. Genet. Epidemiol. 2016;40:597\u2013608.","journal-title":"Genet. Epidemiol"},{"key":"2939_CR39","doi-asserted-by":"publisher","first-page":"481","DOI":"10.1038\/ng.3538","volume":"48","author":"ZH Zhu","year":"2016","unstructured":"Zhu ZH, Zhang FT, Hu H, Bakshi A, Robinson MR, Powell JE, et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets. Nat. Genet. 2016;48:481.","journal-title":"Nat. Genet"},{"key":"2939_CR40","doi-asserted-by":"publisher","first-page":"e34408","DOI":"10.7554\/eLife.34408","volume":"7","author":"G Hemani","year":"2018","unstructured":"Hemani G, Zheng J, Elsworth B, Wade KH, Haberland V, Baird D, et al. The MR-Base platform supports systematic causal inference across the human phenome. Elife. 2018;7:e34408.","journal-title":"Elife"},{"key":"2939_CR41","doi-asserted-by":"publisher","first-page":"e224071","DOI":"10.1001\/jamanetworkopen.2022.4071","volume":"5","author":"MP Pase","year":"2022","unstructured":"Pase MP, Rowsthorn E, Cavuoto MG, Lavale A, Yassi N, Maruff P, et al. Association of neighborhood-level socioeconomic measures with cognition and dementia risk in Australian adults. JAMA Netw. Open. 2022;5:e224071\u2013e71.","journal-title":"JAMA Netw. Open"},{"key":"2939_CR42","doi-asserted-by":"publisher","first-page":"eabm2923","DOI":"10.1126\/sciadv.abm2923","volume":"8","author":"H Kweon","year":"2022","unstructured":"Kweon H, Aydogan G, Dagher A, Bzdok D, Ruff CC, Nave G, et al. Human brain anatomy reflects separable genetic and environmental components of socioeconomic status. Sci. Adv. 2022;8:eabm2923.","journal-title":"Sci. Adv"},{"key":"2939_CR43","doi-asserted-by":"publisher","first-page":"2210","DOI":"10.1093\/brain\/awq185","volume":"133","author":"C Brayne","year":"2010","unstructured":"Brayne C, Ince PG, Keage HAD, McKeith IG, Matthews FE, Polvikoski T, et al. Education, the brain and dementia: neuroprotection or compensation?: EClipSE Collaborative Members. Brain. 2010;133:2210\u201316.","journal-title":"Brain"},{"key":"2939_CR44","doi-asserted-by":"publisher","first-page":"4923","DOI":"10.18632\/aging.102088","volume":"11","author":"YJ Chen","year":"2019","unstructured":"Chen YJ, Lv CL, Li X, Zhang JY, Chen KW, Liu ZW, et al. The positive impacts of early-life education on cognition, leisure activity, and brain structure in healthy aging. Aging. 2019;11:4923\u201342.","journal-title":"Aging"},{"key":"2939_CR45","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-022-28735-5","volume":"13","author":"R Daviet","year":"2022","unstructured":"Daviet R, Aydogan G, Jagannathan K, Spilka N, Koellinger PD, Kranzler HR, et al. Associations between alcohol consumption and gray and white matter volumes in the UK Biobank. Nat. Commun. 2022;13:1175.","journal-title":"Nat. Commun"},{"key":"2939_CR46","doi-asserted-by":"publisher","unstructured":"Peng B, Yang Q, B Joshi R, Liu Y, Akbar M, Song B-J, et al. Role of alcohol drinking in Alzheimer\u2019s disease, Parkinson\u2019s disease, and amyotrophic lateral Sclerosis. Int J Mol Sci. https:\/\/doi.org\/10.3390\/ijms21072316.","DOI":"10.3390\/ijms21072316"},{"key":"2939_CR47","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.drugalcdep.2018.08.009","volume":"192","author":"TC Durazzo","year":"2018","unstructured":"Durazzo TC, Meyerhoff DJ, Yoder KK. Cigarette smoking is associated with cortical thinning in anterior frontal regions, insula and regions showing atrophy in early Alzheimer\u2019s Disease. Drug Alcohol Depend. 2018;192:277\u201384.","journal-title":"Drug Alcohol Depend"},{"key":"2939_CR48","first-page":"912","volume":"48","author":"V Gallo","year":"2019","unstructured":"Gallo V, Vineis P, Cancellieri M, Chiodini P, Barker RA, Brayne C, et al. Exploring causality of the association between smoking and Parkinson\u2019s disease. Int. J. Epidemiol. 2019;48:912\u201325.","journal-title":"Int. J. Epidemiol"},{"key":"2939_CR49","doi-asserted-by":"publisher","first-page":"3207","DOI":"10.1093\/bioinformatics\/btw373","volume":"32","author":"JR Staley","year":"2016","unstructured":"Staley JR, Blackshaw J, Kamat MA, Ellis S, Surendran P, Sun BB, et al. PhenoScanner: a database of human genotype-phenotype associations. Bioinformatics. 2016;32:3207\u201309.","journal-title":"Bioinformatics"},{"key":"2939_CR50","doi-asserted-by":"publisher","first-page":"4851","DOI":"10.1093\/bioinformatics\/btz469","volume":"35","author":"MA Kamat","year":"2019","unstructured":"Kamat MA, Blackshaw JA, Young R, Surendran P, Burgess S, Danesh J, et al. PhenoScanner V2: an expanded tool for searching human genotype-phenotype associations. Bioinformatics. 2019;35:4851\u201353.","journal-title":"Bioinformatics"},{"key":"2939_CR51","doi-asserted-by":"publisher","first-page":"D1005","DOI":"10.1093\/nar\/gky1120","volume":"47","author":"A Buniello","year":"2019","unstructured":"Buniello A, MacArthur JAL, Cerezo M, Harris LW, Hayhurst J, Malangone C, et al. The NHGRI-EBI GWAS Catalog of published genome-wide association studies, targeted arrays and summary statistics 2019. Nucleic Acids Res. 2019;47:D1005\u2013D12.","journal-title":"Nucleic Acids Res"},{"key":"2939_CR52","doi-asserted-by":"publisher","first-page":"755","DOI":"10.1093\/ije\/dyr036","volume":"40","author":"S Burgess","year":"2011","unstructured":"Burgess S, Thompson SG, Collaboration CCG. Avoiding bias from weak instruments in Mendelian randomization studies. Int. J. Epidemiol. 2011;40:755\u201364.","journal-title":"Int. J. Epidemiol"},{"key":"2939_CR53","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1002\/gepi.21758","volume":"37","author":"S Burgess","year":"2013","unstructured":"Burgess S, Butterworth A, Thompson SG. Mendelian randomization analysis with multiple genetic variants using summarized data. Genet Epidemiol. 2013;37:658\u201365.","journal-title":"Genet Epidemiol"},{"key":"2939_CR54","doi-asserted-by":"publisher","first-page":"186","DOI":"10.12688\/wellcomeopenres.15555.1","volume":"4","author":"S Burgess","year":"2019","unstructured":"Burgess S, Davey Smith G, Davies NM, Dudbridge F, Gill D, Glymour MM, et al. Guidelines for performing Mendelian randomization investigations. Wellcome Open Res. 2019;4:186.","journal-title":"Wellcome Open Res"},{"key":"2939_CR55","doi-asserted-by":"publisher","first-page":"377","DOI":"10.1007\/s10654-017-0255-x","volume":"32","author":"S Burgess","year":"2017","unstructured":"Burgess S, Thompson SG. Interpreting findings from Mendelian randomization using the MR-Egger method. Eur. J. Epidemiol. 2017;32:377\u201389.","journal-title":"Eur. J. Epidemiol"},{"key":"2939_CR56","doi-asserted-by":"publisher","first-page":"304","DOI":"10.1002\/gepi.21965","volume":"40","author":"J Bowden","year":"2016","unstructured":"Bowden J, Davey Smith G, Haycock PC, Burgess S. Consistent estimation in Mendelian randomization with some invalid instruments using a weighted median estimator. Genet Epidemiol. 2016;40:304\u201314.","journal-title":"Genet Epidemiol"},{"key":"2939_CR57","doi-asserted-by":"publisher","first-page":"1153","DOI":"10.1093\/genetics\/163.3.1153","volume":"163","author":"BG Milligan","year":"2003","unstructured":"Milligan BG. Maximum-likelihood estimation of relatedness. Genetics. 2003;163:1153\u201367.","journal-title":"Genetics"},{"key":"2939_CR58","doi-asserted-by":"publisher","first-page":"1742","DOI":"10.1214\/19-AOS1866","volume":"48","author":"Q Zhao","year":"2020","unstructured":"Zhao Q, Wang J, Hemani G, Bowden J, Small DS. Statistical inference in two-sample summary-data Mendelian randomization using robust adjusted profile score. Ann. Stat. 2020;48:1742\u201369.","journal-title":"Ann. Stat"},{"key":"2939_CR59","doi-asserted-by":"publisher","first-page":"2333","DOI":"10.1177\/0962280215597579","volume":"26","author":"S Burgess","year":"2017","unstructured":"Burgess S, Small DS, Thompson SG. A review of instrumental variable estimators for Mendelian randomization. Stat. Methods Med Res. 2017;26:2333\u201355.","journal-title":"Stat. Methods Med Res"},{"key":"2939_CR60","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1086\/383251","volume":"74","author":"DR Nyholt","year":"2004","unstructured":"Nyholt DR. A simple correction for multiple testing for single-nucleotide polymorphisms in linkage disequilibrium with each other. Am. J. Hum. Genet. 2004;74:765\u201369.","journal-title":"Am. J. Hum. Genet"},{"key":"2939_CR61","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1038\/sj.hdy.6800717","volume":"95","author":"J Li","year":"2005","unstructured":"Li J, Ji L. Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity. 2005;95:221\u201327.","journal-title":"Heredity"},{"key":"2939_CR62","doi-asserted-by":"publisher","first-page":"2926","DOI":"10.1002\/sim.6522","volume":"34","author":"FD Greco M","year":"2015","unstructured":"Greco M FD, Minelli C, Sheehan NA, Thompson JR. Detecting pleiotropy in Mendelian randomisation studies with summary data and a continuous outcome. Stat. Med. 2015;34:2926\u201340.","journal-title":"Stat. Med"},{"key":"2939_CR63","doi-asserted-by":"publisher","first-page":"693","DOI":"10.1038\/s41588-018-0099-7","volume":"50","author":"M Verbanck","year":"2018","unstructured":"Verbanck M, Chen C-Y, Neale B, Do R. Detection of widespread horizontal pleiotropy in causal relationships inferred from Mendelian randomization between complex traits and diseases. Nat. Genet. 2018;50:693\u201398.","journal-title":"Nat. Genet"},{"key":"2939_CR64","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1093\/ije\/dyv080","volume":"44","author":"J Bowden","year":"2015","unstructured":"Bowden J, Davey Smith G, Burgess S. Mendelian randomization with invalid instruments: effect estimation and bias detection through Egger regression. Int J. Epidemiol. 2015;44:512\u201325.","journal-title":"Int J. Epidemiol"},{"key":"2939_CR65","doi-asserted-by":"publisher","first-page":"1466","DOI":"10.1038\/s41380-023-02025-y","volume":"28","author":"G Li","year":"2023","unstructured":"Li G, Hu Y, Zhang W, Wang J, Ji W, Manza P, et al. Brain functional and structural magnetic resonance imaging of obesity and weight loss interventions. Mol. Psychiatr. 2023;28:1466\u201379.","journal-title":"Mol. Psychiatr"},{"key":"2939_CR66","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1016\/j.lfs.2017.06.002","volume":"182","author":"JN Mazon","year":"2017","unstructured":"Mazon JN, de Mello AH, Ferreira GK, Rezin GT. The impact of obesity on neurodegenerative diseases. Life Sci. 2017;182:22\u20138.","journal-title":"Life Sci"},{"key":"2939_CR67","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1002\/alz.12871","volume":"19","author":"A Carey","year":"2023","unstructured":"Carey A, Fossati S. Hypertension and hyperhomocysteinemia as modifiable risk factors for Alzheimer\u2019s disease and dementia: New evidence, potential therapeutic strategies, and biomarkers. Alzheimer\u2019s. Dement. 2023;19:671\u201395.","journal-title":"Alzheimer\u2019s. Dement"},{"key":"2939_CR68","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1093\/eurheartj\/ehad187","volume":"44","author":"EL Schiffrin","year":"2023","unstructured":"Schiffrin EL, Engert JC. Hypertension, brain imaging phenotypes, and cognitive impairment: Lessons from Mendelian randomization. Eur. Heart J. 2023;44:2126\u201328.","journal-title":"Eur. Heart J"},{"key":"2939_CR69","doi-asserted-by":"publisher","first-page":"301","DOI":"10.1146\/annurev-genom-091212-153455","volume":"14","author":"J Trowsdale","year":"2013","unstructured":"Trowsdale J, Knight JC. Major histocompatibility complex genomics and human disease. Annu. Rev. Genomics Hum. Genet. 2013;14:301\u201323.","journal-title":"Annu. Rev. Genomics Hum. Genet"},{"key":"2939_CR70","doi-asserted-by":"publisher","first-page":"922","DOI":"10.1093\/ije\/dyu005","volume":"43","author":"S Burgess","year":"2014","unstructured":"Burgess S. Sample size and power calculations in Mendelian randomization with a single instrumental variable and a binary outcome. Int J. Epidemiol. 2014;43:922\u201329.","journal-title":"Int J. Epidemiol"},{"key":"2939_CR71","doi-asserted-by":"publisher","first-page":"1096","DOI":"10.1016\/j.neuron.2019.04.023","volume":"102","author":"HG Yi","year":"2019","unstructured":"Yi HG, Leonard MK, Chang EF. The encoding of speech sounds in the superior temporal gyrus. Neuron. 2019;102:1096\u2013110.","journal-title":"Neuron"},{"key":"2939_CR72","doi-asserted-by":"publisher","first-page":"1064667","DOI":"10.3389\/fnagi.2022.1064667","volume":"14","author":"Y Xiao","year":"2022","unstructured":"Xiao Y, Wang J, Huang K, Gao L, Yao S. Progressive structural and covariance connectivity abnormalities in patients with Alzheimer\u2019s disease. Front Aging Neurosci. 2022;14:1064667.","journal-title":"Front Aging Neurosci"},{"key":"2939_CR73","doi-asserted-by":"publisher","first-page":"3042","DOI":"10.1016\/j.cub.2017.08.061","volume":"27","author":"I Tsutsui-Kimura","year":"2017","unstructured":"Tsutsui-Kimura I, Natsubori A, Mori M, Kobayashi K, Drew MR, de Kerchove d\u2019Exaerde A, et al. Distinct roles of ventromedial versus ventrolateral striatal medium spiny neurons in reward-oriented behavior. Curr. Biol. 2017;27:3042\u20133048.e4.","journal-title":"Curr. Biol"},{"key":"2939_CR74","doi-asserted-by":"publisher","first-page":"532","DOI":"10.1016\/j.jalz.2011.05.2410","volume":"7","author":"CG Lyketsos","year":"2011","unstructured":"Lyketsos CG, Carrillo MC, Ryan JM, Khachaturian AS, Trzepacz P, Amatniek J, et al. Neuropsychiatric symptoms in Alzheimer\u2019s disease. Alzheimers Dement. 2011;7:532\u201339.","journal-title":"Alzheimers Dement"},{"key":"2939_CR75","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.3233\/JAD-190954","volume":"75","author":"L Iaccarino","year":"2020","unstructured":"Iaccarino L, Sala A, Caminiti SP, Presotto L, Perani D. In vivo MRI structural and PET metabolic connectivity study of dopamine pathways in Alzheimer\u2019s disease. J. Alzheimers Dis. 2020;75:1003\u201316.","journal-title":"J. Alzheimers Dis"},{"key":"2939_CR76","doi-asserted-by":"publisher","first-page":"1672","DOI":"10.1016\/S0140-6736(15)00461-4","volume":"386","author":"J Bang","year":"2015","unstructured":"Bang J, Spina S, Miller BL. Frontotemporal dementia. Lancet. 2015;386:1672\u201382.","journal-title":"Lancet"},{"key":"2939_CR77","doi-asserted-by":"publisher","first-page":"563","DOI":"10.1007\/s00234-019-02357-z","volume":"62","author":"J Blaauw","year":"2020","unstructured":"Blaauw J, Meiners LC. The splenium of the corpus callosum: embryology, anatomy, function and imaging with pathophysiological hypothesis. Neuroradiology. 2020;62:563\u201385.","journal-title":"Neuroradiology"},{"key":"2939_CR78","doi-asserted-by":"publisher","first-page":"4163","DOI":"10.1002\/hbm.22468","volume":"35","author":"CJ Mahoney","year":"2014","unstructured":"Mahoney CJ, Ridgway GR, Malone IB, Downey LE, Beck J, Kinnunen KM, et al. Profiles of white matter tract pathology in frontotemporal dementia. Hum. Brain Mapp. 2014;35:4163\u201379.","journal-title":"Hum. Brain Mapp"},{"key":"2939_CR79","doi-asserted-by":"publisher","first-page":"1025","DOI":"10.1002\/acn3.601","volume":"5","author":"LC Jiskoot","year":"2018","unstructured":"Jiskoot LC, Bocchetta M, Nicholas JM, Cash DM, Thomas D, Modat M, et al. Presymptomatic white matter integrity loss in familial frontotemporal dementia in the GENFI cohort: A cross-sectional diffusion tensor imaging study. Ann. Clin. Transl. Neurol. 2018;5:1025\u201336.","journal-title":"Ann. Clin. Transl. Neurol"},{"key":"2939_CR80","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.3171\/2020.7.JNS192846","volume":"135","author":"IL Maldonado","year":"2021","unstructured":"Maldonado IL, Destrieux C, Ribas EC, Guimaraes BSDB, Cruz PP, Duffau H. Composition and organization of the sagittal stratum in the human brain: a fiber dissection study. J. Neurosurg. 2021;135:1214\u201322.","journal-title":"J. Neurosurg"},{"key":"2939_CR81","doi-asserted-by":"publisher","first-page":"2705","DOI":"10.1093\/cercor\/bhr288","volume":"22","author":"F Agosta","year":"2012","unstructured":"Agosta F, Scola E, Canu E, Marcone A, Magnani G, Sarro L, et al. White matter damage in frontotemporal lobar degeneration spectrum. Cereb. Cortex. 2012;22:2705\u201314.","journal-title":"Cereb. Cortex"},{"key":"2939_CR82","doi-asserted-by":"publisher","first-page":"e53470","DOI":"10.7554\/eLife.53470","volume":"9","author":"V Menon","year":"2020","unstructured":"Menon V, Gallardo G, Pinsk MA, Nguyen VD, Li JR, Cai W, et al. Microstructural organization of human insula is linked to its macrofunctional circuitry and predicts cognitive control. Elife. 2020;9:e53470.","journal-title":"Elife"},{"key":"2939_CR83","doi-asserted-by":"publisher","first-page":"41","DOI":"10.3390\/bioengineering10010041","volume":"10","author":"S Ziccardi","year":"2022","unstructured":"Ziccardi S, Pizzini FB, Guandalini M, Tamanti A, Cristofori C, Calabrese M. Making visible the invisible: automatically measured global and regional brain volume is associated with cognitive impairment and fatigue in multiple sclerosis. Bioengineering. 2022;10:41.","journal-title":"Bioengineering"},{"key":"2939_CR84","doi-asserted-by":"publisher","first-page":"1683","DOI":"10.1016\/S0140-6736(15)00462-6","volume":"386","author":"Z Walker","year":"2015","unstructured":"Walker Z, Possin KL, Boeve BF, Aarsland D. Lewy body dementias. Lancet. 2015;386:1683\u201397.","journal-title":"Lancet"},{"key":"2939_CR85","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1093\/brain\/awac094","volume":"145","author":"R Mehraram","year":"2022","unstructured":"Mehraram R, Peraza LR, Murphy NRE, Cromarty RA, Graziadio S, O\u2019Brien JT, et al. Functional and structural brain network correlates of visual hallucinations in Lewy body dementia. Brain. 2022;145:2190\u2013205.","journal-title":"Brain"},{"key":"2939_CR86","doi-asserted-by":"publisher","first-page":"102200","DOI":"10.1016\/j.nicl.2020.102200","volume":"25","author":"N Nicastro","year":"2020","unstructured":"Nicastro N, Mak E, Williams GB, Surendranathan A, Bevan-Jones WR, Passamonti L, et al. Correlation of microglial activation with white matter changes in dementia with Lewy bodies. Neuroimage Clin. 2020;25:102200.","journal-title":"Neuroimage Clin"},{"key":"2939_CR87","doi-asserted-by":"publisher","first-page":"208","DOI":"10.3389\/fnagi.2015.00208","volume":"7","author":"S Delli Pizzi","year":"2015","unstructured":"Delli Pizzi S, Franciotti R, Taylor J-P, Esposito R, Tartaro A, Thomas A, et al. Structural connectivity is differently altered in dementia with lewy body and Alzheimer\u2019s disease. Front Aging Neurosci. 2015;7:208.","journal-title":"Front Aging Neurosci"},{"key":"2939_CR88","doi-asserted-by":"publisher","first-page":"bhad496","DOI":"10.1093\/cercor\/bhad496","volume":"34","author":"Y Wang","year":"2024","unstructured":"Wang Y, Shen O, Xu Q, Sun L, Jia Y, Liu Y, et al. Genetic analyses identify brain imaging-derived phenotypes associated with the risk of amyotrophic lateral sclerosis. Cereb. Cortex. 2024;34:bhad496.","journal-title":"Cereb. Cortex"},{"key":"2939_CR89","doi-asserted-by":"publisher","first-page":"1026","DOI":"10.1093\/aje\/kwx246","volume":"186","author":"A Fry","year":"2017","unstructured":"Fry A, Littlejohns TJ, Sudlow C, Doherty N, Adamska L, Sprosen T, et al. Comparison of sociodemographic and health-related characteristics of UK Biobank participants with those of the general population. Am. J. Epidemiol. 2017;186:1026\u201334.","journal-title":"Am. J. Epidemiol"}],"container-title":["Translational Psychiatry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02939-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02939-3","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02939-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,28]],"date-time":"2024-05-28T05:02:14Z","timestamp":1716872534000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41398-024-02939-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,5,28]]},"references-count":89,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["2939"],"URL":"https:\/\/doi.org\/10.1038\/s41398-024-02939-3","relation":{},"ISSN":["2158-3188"],"issn-type":[{"value":"2158-3188","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,5,28]]},"assertion":[{"value":"14 September 2023","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"10 May 2024","order":2,"name":"revised","label":"Revised","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"16 May 2024","order":3,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"28 May 2024","order":4,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors report no competing interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}},{"value":"All the datasets in our study are publicly available GWAS summary statistics, and hence no additional ethical approval and participants\u2019 consent was required. Detailed ethical approval and participants\u2019 consent can be found in the original GWAS publications.","order":2,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethics approval and consent to participate"}}],"article-number":"215"}}