TY - JOUR
T1 - Meta-analysis of genome-wide association studies of hoarding symptoms in 27,537 individuals
AU - Strom, N.I.
AU - Smit, D.J.A.
AU - Silzer, T.
AU - Iyegbe, C.
AU - Burton, C.L.
AU - Pool, R.
AU - Lemire, M.
AU - Crowley, J.J.
AU - Hottenga, J.-J.
AU - Ivanov, V.Z.
AU - Larsson, H.
AU - Lichtenstein, P.
AU - Magnusson, P.
AU - Rück, C.
AU - Schachar, R.J.
AU - Wu, H.M.
AU - Meier, S.M.
AU - Crosbie, J.
AU - Arnold, P.D.
AU - Mattheisen, M.
AU - Boomsma, D.I.
AU - Mataix-Cols, D.
AU - Cath, D.
N1 - Funding Information: We acknowledge The Swedish Twin Registry (STR) for data access. The STR is managed by Karolinska Institutet and receives funding through the Swedish Research Council under the grant no 2017-00641. The computations/data handling were enabled by resources provided by the Swedish National Infrastructure for Computing (SNIC) at Uppmax partially funded by the Swedish Research Council through grant agreement no. 2018-05973. The Netherlands Twin Register (NTR) warmly thanks all twin families for their participation. NTR is supported by multiple grants from the Netherlands Organisations for Scientific Research (NWO) and Medical Research (ZonMW): Netherlands Twin Registry Repository (NWO 480-15-001/674); the Biobank-based integrative omics study (BIOS) funded by BBMRI-NL (NWO projects 184.021.007 and 184.033.111); the European Science Council (ERC) Genetics of Mental Illness (ERC Advanced, 230374, PI Boomsma); the Royal Netherlands Academy of Science Professor Award (PAH/6635) to DIB; Rutgers University Cell and DNA Repository (NIMH U24 MH068457-06), the Avera Institute, Sioux Falls, South Dakota (USA) and the National Institutes of Health (NIH R01 HD042157-01A1). Part of the genotyping was funded by the Genetic Association Information Network (GAIN) of the Foundation for the National Institutes of Health and Grand Opportunity grants (1RC2 MH089951). TwinsUK is funded by the Wellcome Trust, Medical Research Council, Versus Arthritis, European Union Horizon 2020, Chronic Disease Research Foundation (CDRF), Zoe Ltd, the National Institute for Health and Care Research (NIHR) Clinical Research Network (CRN) and Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust in partnership with King’s College London. Spit for Science was supported by the Canadian Institutes of Health Research (RJS, MOP‐93696 and PDA, MOP‐106573). Dr. Arnold is supported by the Alberta Innovates Translational Health Chair in Child and Youth Mental Health. We acknowledge support by the Open Access Publication Fund of Humboldt-Universität zu Berlin. Publisher Copyright: © 2022, The Author(s).
PY - 2022/12/1
Y1 - 2022/12/1
N2 - © 2022, The Author(s).Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26–48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a “gene discovery zone”. To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.
AB - © 2022, The Author(s).Hoarding Disorder (HD) is a mental disorder characterized by persistent difficulties discarding or parting with possessions, often resulting in cluttered living spaces, distress, and impairment. Its etiology is largely unknown, but twin studies suggest that it is moderately heritable. In this study, we pooled phenotypic and genomic data from seven international cohorts (N = 27,537 individuals) and conducted a genome wide association study (GWAS) meta-analysis of parent- or self-reported hoarding symptoms (HS). We followed up the results with gene-based and gene-set analyses, as well as leave-one-out HS polygenic risk score (PRS) analyses. To examine a possible genetic association between hoarding symptoms and other phenotypes we conducted cross-trait PRS analyses. Though we did not report any genome-wide significant SNPs, we report heritability estimates for the twin-cohorts between 26–48%, and a SNP-heritability of 11% for an unrelated sub-cohort. Cross-trait PRS analyses showed that the genetic risk for schizophrenia and autism spectrum disorder were significantly associated with hoarding symptoms. We also found suggestive evidence for an association with educational attainment. There were no significant associations with other phenotypes previously linked to HD, such as obsessive-compulsive disorder, depression, anxiety, or attention-deficit hyperactivity disorder. To conclude, we found that HS are heritable, confirming and extending previous twin studies but we had limited power to detect any genome-wide significant loci. Much larger samples will be needed to further extend these findings and reach a “gene discovery zone”. To move the field forward, future research should not only include genetic analyses of quantitative hoarding traits in larger samples, but also in samples of individuals meeting strict diagnostic criteria for HD, and more ethnically diverse samples.
UR - http://www.scopus.com/inward/record.url?scp=85141884281&partnerID=8YFLogxK
U2 - https://doi.org/10.1038/s41398-022-02248-7
DO - https://doi.org/10.1038/s41398-022-02248-7
M3 - Article
C2 - 36379924
SN - 2158-3188
VL - 12
JO - Translational Psychiatry
JF - Translational Psychiatry
IS - 1
M1 - 479
ER -