BACKGROUND: Intracranial aneurysms (IAs), abdominal aortic aneurysms (AAAs), and thoracic aortic aneurysms (TAAs) all have a familial predisposition. Given that aneurysm types are known to co-occur, we hypothesized that there may be shared genetic risk factors for IAs, AAAs, and TAAs. METHODS AND RESULTS: We performed a mega-analysis of 1000 Genomes Project-imputed genome-wide association study (GWAS) data of 4 previously published aneurysm cohorts: 2 IA cohorts (in total 1516 cases, 4305 controls), 1 AAA cohort (818 cases, 3004 controls), and 1 TAA cohort (760 cases, 2212 controls), and observed associations of 4 known IA, AAA, and/or TAA risk loci (9p21, 18q11, 15q21, and 2q33) with consistent effect directions in all 4 cohorts. We calculated polygenic scores based on IA-, AAA-, and TAA-associated SNPs and tested these scores for association to case-control status in the other aneurysm cohorts; this revealed no shared polygenic effects. Similarly, linkage disequilibrium-score regression analyses did not show significant correlations between any pair of aneurysm subtypes. Last, we evaluated the evidence for 14 previously published aneurysm risk single-nucleotide polymorphisms through collaboration in extended aneurysm cohorts, with a total of 6548 cases and 16 843 controls (IA) and 4391 cases and 37 904 controls (AAA), and found nominally significant associations for IA risk locus 18q11 near RBBP8 to AAA (odds ratio [OR]=1.11; P=4.1×10(-5)) and for TAA risk locus 15q21 near FBN1 to AAA (OR=1.07; P=1.1×10(-3)). CONCLUSIONS: Although there was no evidence for polygenic overlap between IAs, AAAs, and TAAs, we found nominally significant effects of two established risk loci for IAs and TAAs in AAAs. These two loci will require further replication. ; van ’t Hof is supported by a grant of the Dutch Heart Foundation (NHS; Project No. 2008B004). Ruigrok is supported by a clinical fellowship grant of the Netherlands Organization for Scientific Research (NWO; Project No. 40‐00703‐98‐13533). Baas is supported by a grant from the Dr E. Dekker Program of the Netherlands Heart Foundation (2009T001). Bown is supported by a HEFCE Clinical Senior Lecturer Fellowship. Broderick is supported by a Familial Intracranial Aneurysm (FIA) grant (R01NS39512). Foroud is supported by an FIA grant (R03NS083468). Kubo is funded by the Instrumentarium Science Foundation, Finland, and by the Finnish Foundation for Cardiovascular Research, University of Eastern Finland. Saratzis is an NIHR Academic Clinical Lecturer. Milewicz is supported by grants from the National Institutes of Health (NIH; P50‐HL083794). The generation and management of GWAS genotype data for the Rotterdam Study (RS I, RS II, and RS III) was executed by the Human Genotyping Facility of the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, Rotterdam, The Netherlands. The GWAS data sets are supported by the Netherlands Organization of Scientific Research NWO Investments (No. 175.010.2005.011, 911‐03‐012), the Genetic Laboratory of the Department of Internal Medicine, Erasmus MC, the Research Institute for Diseases in the Elderly (014‐93‐015; RIDE2), the Netherlands Genomics Initiative (NGI)/Netherlands Organization for Scientific Research (NWO), Netherlands Consortium for Healthy Aging (NCHA; Project No. 050‐060‐810). The Rotterdam Study is funded by Erasmus Medical Center and Erasmus University, Rotterdam, Netherlands Organization for the Health Research and Development (ZonMw), the Research Institute for Diseases in the Elderly (RIDE), the Ministry of Education, Culture and Science, the Ministry for Health, Welfare and Sports, the European Commission (DG XII), and the Municipality of Rotterdam. The Japanese IA GWAS (named “Japan 2” in this study) was conducted as part of the Biobank Japan Project that was supported by the Ministry of Education, Culture, Sports, Sciences and Technology, Japan. For the “USA+” IA GWAS, infrastructure was partly supported by Grant No. UL1RR025005, a component of the NIH and NIH Roadmap for Medical Research. This study was also supported by the National Health and Medical Research Council (NHMRC), Australia, and the Health Research Council of New Zealand. Additional funding was provided by a grant from Jagiellonian University Medical College K/ZDS/001456. The study also contains data from Atherosclerosis Risk in Communities, which is performed as a collaborative study supported by National Heart, Lung, and Blood Institute contracts (HHSN268201100005C, HHSN268201100006C, HHSN268201100007C, HHSN268201100008C, HHSN268201100009C, HHSN268201100010C, HHSN268201100011C, and HHSN26820110012C), R01HL087641, R01HL59367, and R01HL086694; National Human Genome Research Institute contract U01HG004402; and NIH contract HHSN268200625226C. Neurocognitive data were collected by U01 HL096812, HL096814, HL096899, HL096902, and HL096917 with previous brain MRI examinations funded by R01‐HL70825. The @neurIST project is supported by the 6th framework program of the European Commission (www.aneurist.org) FP6‐IST‐2004–027703. AAA GWAS data provided by the Aneurysm Consortium were funded by the Wellcome Trust (Award No. 084695) and makes use of data generated by the WTCCC. A full list of the investigators who contributed to the generation of the data is available from www.wtccc.org.uk. Funding for the WTCCC project was provided by the Wellcome Trust under awards 076113 and 085475. Funding for the New Zealand project was provided by the Health Research Council of New Zealand (08‐75, 14‐155). The Geisinger project was funded, in part, by the Pennsylvania Commonwealth Universal Research Enhancement Program, the Geisinger Clinical Research Fund, the American Heart Association, and the Ben Franklin Technology Development Fund of Pennsylvania. The eMERGE Network is funded by the NHGRI, with additional funding from the NIGMS through the following grants: U01HG004438 to Johns Hopkins University; U01HG004424 to The Broad Institute; U01HG004438 to CIDR; U01HG004610 and U01HG006375 to Group Health Cooperative; U01HG004608 to Marshfield Clinic; U01HG006389 to Essentia Institute of Rural Health; U01HG04599 and U01HG006379 to Mayo Clinic; U01HG004609 and U01HG006388 to Northwestern University; U01HG04603 and U01HG006378 to Vanderbilt University; U01HG006385 to the Coordinating Center; U01HG006382 to Geisinger Health System; and U01HG006380 to Icahn School of Medicine Mount Sinai. Vanderbilt's data set(s) used for the analyses described were obtained from Vanderbilt University Medical Center's BioVU, which is supported by institutional funding and by the National Center for Research Resources (Grant UL1 RR024975‐01; which is now at the National Center for Advancing Translational Sciences: Grant 2 UL1 TR000445‐06). The project that created the data regarding the TAA cohort was supported by grants from the NIH (P50‐HL083794 and R01‐HL62594; UL1RR024148 and UL1RR025758 [CTSA]; K08‐HL080085), as well as the Doris Duke Charitable Trust, the Vivian L. Smith Foundation, the TexGen Foundation, and the Thoracic Surgery Foundation for Research and Education. ; Peer-reviewed ; Publisher Version