The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Genomic inflation factors under polygenic inheritance
Open accessAbstract
Population structure, including population stratification and cryptic relatedness, can cause spurious associations in genome-wide association studies (GWAS). Usually, the scaled median or mean test statistic for association calculated from multiple single-nucleotide-polymorphisms across the genome is used to assess such effects, and 'genomic control' can be applied subsequently to adjust test statistics at individual loci by a genomic inflation factor. Published GWAS have clearly shown that there are many loci underlying genetic variation for a wide range of complex diseases and traits, implying that a substantial proportion of the genome should show inflation of the test statistic. Here, we show by theory, simulation and analysis of data that in the absence of population structure and other technical artefacts, but in the presence of polygenic inheritance, substantial genomic inflation is expected. Its magnitude depends on sample size, heritability, linkage disequilibrium structure and the number of causal variants. Our predictions are consistent with empirical observations on height in independent samples of ~4000 and ~133,000 individuals.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
PLINK: a tool set for whole-genome association and population-based linkage analyses.
Purcell, S., Neale, B., Todd-Brown, K., Thomas, L., Ferreira, M. A. R., Bender, D., Maller, J., Sklar, P., de Bakker, P. I. W., Daly, M. J., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/519795 · Cited by 34,089
Self-citationGenome-wide association study of 14,000 cases of seven common diseases and 3,000 shared controls
The Wellcome Trust Case Control Consortium, Management Committee, Burton, P. R., Clayton, D. G., Cardon, L. R., Craddock, N., Deloukas, P., Duncanson, A., Kwiatkowski, D. P., McCarthy, M. I., et al. (2007) · Nature · doi:10.1038/nature05911 · Cited by 9,442
Self-citationFinding the missing heritability of complex diseases
Manolio, T. A., Collins, F. S., Cox, N. J., Goldstein, D. B., Hindorff, L. A., Hunter, D. J., McCarthy, M. I., Ramos, E. M., Cardon, L. R., Chakravarti, A., et al. (2009) · Nature · doi:10.1038/nature08494 · Cited by 8,336
Self-citationCommon polygenic variation contributes to risk of schizophrenia and bipolar disorder
The International Schizophrenia Consortium (2009) · Nature · doi:10.1038/nature08185 · Cited by 4,821
Hindorff, L. A., Sethupathy, P., Junkins, H. A., Ramos, E. M., Mehta, J. P., Collins, F. S., & Manolio, T. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0903103106 · Cited by 4,013
Biological, clinical and population relevance of 95 loci for blood lipids
Teslovich, T. M., Musunuru, K., Smith, A. V., Edmondson, A. C., Stylianou, I. M., Koseki, M., Pirruccello, J. P., Ripatti, S., Chasman, D. I., Willer, C. J., et al. (2010) · Nature · doi:10.1038/nature09270 · Cited by 3,487
Self-citationGenomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162 · cited 1×
“8 One standard quality-control measure for GWAS and meta-analysis is genomic control (GC)”
BackgroundHundreds of variants clustered in genomic loci and biological pathways affect human height
Lango Allen, H., Estrada, K., Lettre, G., Berndt, S. I., Weedon, M. N., Rivadeneira, F., Willer, C. J., Jackson, A. U., Vedantam, S., Raychaudhuri, S., et al. (2010) · Nature · doi:10.1038/nature09410 · Cited by 1,945
Self-citationPersonal genomes: The case of the missing heritability
Maher, B. (2008) · Nature · doi:10.1038/456018a · Cited by 1,737
The effects of human population structure on large genetic association studies
Marchini, J., Cardon, L. R., Phillips, M. S., & Donnelly, P. (2004) · Nature Genetics · doi:10.1038/ng1337 · Cited by 869
Research works printed but not linked: 12
- Speliotes EK, Willer CJ, Berndt SI et al: Association analyses of 249 796 individuals reveal 18 new loci associated with body mass index. Nat Genet 2010; 42: 937–948. · DOI · Paper page
- Heid IM, Jackson AU, Randall JC et al: Meta-analysis identifies 13 new loci associated with waist-hip ratio and reveals sexual dimorphism in the genetic basis of fat distribution. Nat Genet 2010; 42: 949–960. · DOI · Paper page
- Franke A, McGovern DPB, Barrett JC et al: Genome-wide meta-analysis increases to 71 the number of confirmed Crohn's disease susceptibility loci. Nat Genet 2010; 42: 1118–1125. · DOI · Paper page
- Reich DE, Goldstein DB : Detecting association in a case-control study while correcting for population stratification. Genet Epidemiol 2001; 20: 4–16. · doi:10.1002/1098-2272(200101)20:1<4::aid-gepi2>3.0.co;2-t
- Zheng G, Freidlin B, Gastwirth JL : Robust genomic control for association studies. Am J Hum Genet 2006; 78: 350–356. · DOI
- Cardon LR, Palmer LJ : Population stratification and spurious allelic association. The Lancet 2003; 361: 598–604. · DOI · Paper page
- Hao K, Li C, Rosenow C, Wong WH : Detect and adjust for population stratification in population-based association study using genomic control markers: an application of Affymetrix Genechip Human Mapping 10 K array. Eur J Hum Genet 2004; 12: 1001–1006. · DOI
- Chapman JM, Cooper JD, Todd JA, Clayton DG : Detecting disease associations due to linkage disequilibrium using haplotype tags: a class of tests and the determinants of statistical power. Hum Hered 2003; 56: 18–31. · DOI · Paper page
- Spencer CC, Su Z, Donnelly P, Marchini J : Designing genome-wide association studies: sample size, power, imputation, and the choice of genotyping chip. PLoS Genet 2009; 5: e1000477. · DOI · Paper page
- Yang J, Wray NR, Visscher PM : Comparing apples and oranges: equating the power of case-control and quantitative trait association studies. Genet Epidemiol 2010; 34: 254–257. · DOI · Paper page
- Yang J, Benyamin B, McEvoy BP et al: Common SNPs explain a large proportion of the heritability for human height. Nat Genet 2010; 42: 565–569. · DOI · Paper page
- Yang J, Lee SH, Goddard ME, Visscher PM : GCTA: a tool for genome-wide complex trait analysis. Am J Hum Genet 2010; 88: 76–82. · DOI · Paper page
Cited by
Biological insights from 108 schizophrenia-associated genetic loci
Schizophrenia Working Group of the Psychiatric Genomics Consortium (2014) · Nature · doi:10.1038/nature13595 · Cited by 7,577
LD Score regression distinguishes confounding from polygenicity in genome-wide association studies
Schizophrenia Working Group of the Psychiatric Genomics Consortium, Bulik-Sullivan, B. K., Loh, P.-R., Finucane, H. K., Ripke, S., Yang, J., Patterson, N., Daly, M. J., Price, A. L., & Neale, B. M. (2015) · Nature Genetics · doi:10.1038/ng.3211 · Cited by 5,559
Self-citationAn atlas of genetic correlations across human diseases and traits
ReproGen Consortium, Bulik-Sullivan, B., Psychiatric Genomics Consortium, Genetic Consortium for Anorexia Nervosa of the Wellcome Trust Case Control Consortium 3, Finucane, H. K., Anttila, V., Gusev, A., Day, F. R., Loh, P.-R., Duncan, L., et al. (2015) · Nature Genetics · doi:10.1038/ng.3406 · Cited by 4,255
Mapping genomic loci implicates genes and synaptic biology in schizophrenia
Trubetskoy, V., Pardiñas, A. F., Qi, T., Panagiotaropoulou, G., Awasthi, S., Bigdeli, T. B., Bryois, J., Chen, C.-Y., Dennison, C. A., Hall, L. S., et al. (2022) · Nature · doi:10.1038/s41586-022-04434-5 · Cited by 2,964
Self-citationPartitioning heritability by functional annotation using genome-wide association summary statistics
ReproGen Consortium, Finucane, H. K., Schizophrenia Working Group of the Psychiatric Genomics Consortium, The RACI Consortium, Bulik-Sullivan, B., Gusev, A., Trynka, G., Reshef, Y., Loh, P.-R., Anttila, V., et al. (2015) · Nature Genetics · doi:10.1038/ng.3404 · Cited by 2,604
Self-citation
Metadata
- Authors
- the GIANT Consortium, Yang, J., Weedon, M. N., Purcell, S., Lettre, G., Estrada, K., Willer, C. J., Smith, A. V., Ingelsson, E., O'Connell, J. R., Mangino, M., Mägi, R., Madden, P. A., Heath, A. C., Nyholt, D. R., Martin, N. G., Montgomery, G. W., Frayling, T. M., Hirschhorn, J. N., McCarthy, M. I., Goddard, M. E., & Visscher, P. M.
- Venue
- European Journal of Human Genetics
- Published
- 2011-03-16
- Volume
- 19
- Issue
- 7
- Pages
- 807-812
- ISSN
- 1018-4813 (ISSN-L)
- 1476-5438
- OpenAlex
- W2120029762
- Cited by
- 579
- References
- 11
- FWCI
- 14.43
- Type
- journal article
- Language
- en
- Open access
- hybrid
- Licence
- www.springer.com/tdm (tdm)
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
How to cite
Cite CoChat for the checks on this page, and the paper for its own findings.
- This page
- CoChat. (2026). Citation check: Genomic inflation factors under polygenic inheritance. https://app.cochat.ai/papers/10.1038/ejhg.2011.39
- The paper
- the GIANT Consortium, Yang, J., Weedon, M. N., Purcell, S., Lettre, G., Estrada, K., Willer, C. J., Smith, A. V., Ingelsson, E., O'Connell, J. R., Mangino, M., Mägi, R., Madden, P. A., Heath, A. C., Nyholt, D. R., Martin, N. G., Montgomery, G. W., Frayling, T. M., Hirschhorn, J. N., . . . Visscher, P. M. (2011). Genomic inflation factors under polygenic inheritance. European Journal of Human Genetics. https://doi.org/10.1038/ejhg.2011.39
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
