Cited by 553Genetic Associations and EpidemiologyGenetic Syndromes and ImprintingGenetic and phenotypic traits in livestock

The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.

Parental origin of sequence variants associated with complex diseases

Open access

DIAGRAM Consortium, Kong, Augustine, Steinthorsdottir, Valgerdur, Masson, Gisli, Thorleifsson, Gudmar, Sulem, Patrick, Besenbacher, Soren, Jonasdottir, Aslaug, Sigurdsson, Asgeir, Kristinsson, Kari Th., Jonasdottir, Adalbjorg, Frigge, Michael L., Gylfason, Arnaldur, Olason, Pall I., Gudjonsson, Sigurjon A., Sverrisson, Sverrir, Stacey, Simon N., Sigurgeirsson, Bardur, Benediktsdottir, Kristrun R., Sigurdsson, Helgi, Jonsson, Thorvaldur, Benediktsson, Rafn, Olafsson, Jon H., Johannsson, Oskar Th., Hreidarsson, Astradur B., Sigurdsson, Gunnar, Ferguson-Smith, Anne C., Gudbjartsson, Daniel F., Thorsteinsdottir, Unnur, Stefansson, Kari·2009·Nature

DOI 10.1038/nature08625PMC PMC3746295

Open this paper in CoChat — free account

Abstract

Effects of susceptibility variants may depend on from which parent they are inherited. Although many associations between sequence variants and human traits have been discovered through genome-wide associations, the impact of parental origin has largely been ignored. Here we show that for 38,167 Icelanders genotyped using single nucleotide polymorphism (SNP) chips, the parental origin of most alleles can be determined. For this we used a combination of genealogy and long-range phasing. We then focused on SNPs that associate with diseases and are within 500 kilobases of known imprinted genes. Seven independent SNP associations were examined. Five-one with breast cancer, one with basal-cell carcinoma and three with type 2 diabetes-have parental-origin-specific associations. These variants are located in two genomic regions, 11p15 and 7q32, each harbouring a cluster of imprinted genes. Furthermore, we observed a novel association between the SNP rs2334499 at 11p15 and type 2 diabetes. Here the allele that confers risk when paternally inherited is protective when maternally transmitted. We identified a differentially methylated CTCF-binding site at 11p15 and demonstrated correlation of rs2334499 with decreased methylation of that site.

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

Crossref · 10.1038/nature08625

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

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.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Statistical significance for genomewide studies
Storey, J. D., & Tibshirani, R. (2003) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1530509100 · Cited by 9,692
Genomic Control for Association Studies
Devlin, B., & Roeder, K. (1999) · Biometrics · doi:10.1111/j.0006-341x.1999.00997.x · Cited by 3,162
A new multipoint method for genome-wide association studies by imputation of genotypes
Marchini, J., Howie, B., Myers, S., McVean, G., & Donnelly, P. (2007) · Nature Genetics · doi:10.1038/ng2088 · Cited by 2,609
Genome-wide association study identifies novel breast cancer susceptibility loci
Easton, D. F., Pooley, K. A., Dunning, A. M., Pharoah, P. D. P., Thompson, D., Ballinger, D. G., Struewing, J. P., Morrison, J., Field, H., Luben, R., et al. (2007) · Nature · doi:10.1038/nature05887 · Cited by 2,319
Methylation of a CTCF-dependent boundary controls imprinted expression of the Igf2 gene
Bell, A. C., & Felsenfeld, G. (2000) · Nature · doi:10.1038/35013100 · Cited by 1,746
Phenotypic plasticity and the epigenetics of human disease
Feinberg, A. P. (2007) · Nature · doi:10.1038/nature05919 · Cited by 1,613
Genetics of gene expression and its effect on disease
Emilsson, V., Thorleifsson, G., Zhang, B., Leonardson, A. S., Zink, F., Zhu, J., Carlson, S., Helgason, A., Walters, G. B., Gunnarsdottir, S., et al. (2008) · Nature · doi:10.1038/nature06758 · Cited by 1,296
Self-citation
Analysis of the Vertebrate Insulator Protein CTCF-Binding Sites in the Human Genome
Kim, T. H., Abdullaev, Z., Smith, A. D., Ching, K. A., Loukinov, D. I., Green, R. D., Zhang, M. Q., Lobanenkov, V. V., & Ren, B. (2007) · Cell · doi:10.1016/j.cell.2006.12.048 · Cited by 1,022
Variants in KCNQ1 are associated with susceptibility to type 2 diabetes mellitus
Yasuda, K., Miyake, K., Horikawa, Y., Hara, K., Osawa, H., Furuta, H., Hirota, Y., Mori, H., Jonsson, A., Sato, Y., et al. (2008) · Nature Genetics · doi:10.1038/ng.207 · Cited by 776
SNPs in KCNQ1 are associated with susceptibility to type 2 diabetes in East Asian and European populations
Unoki, H., Takahashi, A., Kawaguchi, T., Hara, K., Horikoshi, M., Andersen, G., Ng, D. P. K., Holmkvist, J., Borch-Johnsen, K., Jørgensen, T., et al. (2008) · Nature Genetics · doi:10.1038/ng.208 · Cited by 725

Show all 23 references

Sorted by citations

Items 401–500 of 552

Joint modeling of eQTLs and parent-of-origin effects using an orthogonal framework with RNA-seq data
Deng, S., Hardin, J. W., Amos, C. I., & Xiao, F. (2020) · Human Genetics · doi:10.1007/s00439-020-02162-2 · Cited by 8
Behavioral genetics and animal science
Grandin, T., & Deesing, M. J. (2022) · Elsevier eBooks · doi:10.1016/b978-0-323-85752-9.00005-6 · Cited by 5
An Exploratory Association Analysis of the Insulin Gene Region With Diabetes Mellitus in Two Dog Breeds
Hess, R. S., Henthorn, P. S., Devoto, M., Wang, F., & Feng, R. (2019) · Journal of Heredity · doi:10.1093/jhered/esz059 · Cited by 5
Genome-wide survey of parent-of-origin-specific associations across clinical traits derived from electronic health records
Kim, H. I., Ye, B., Staples, J. C., Marcketta, A., Gao, C., Shuldiner, A. R., & Hout, C. V. V. (2021) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2021.100039 · Cited by 3
“2,8,9 Recently, a study performed genome-wide PoO association analyses for 21 common quantitative traits in a Hutterite population isolate.”
BackgroundMethodInfluential
What is Next for the Genetics of Multiple Sclerosis?
Ramagopalan, S. V., & Dyment, D. A. (2011) · Autoimmune Diseases · doi:10.4061/2011/519450 · Cited by 5
Correction: A Powerful Test of Parent-of-Origin Effects for Quantitative Traits Using Haplotypes
Feng, R., Wu, Y., Jang, G. H., Ordovás, J. M., & Arnett, D. K. (2012) · PLoS ONE · doi:10.1371/annotation/3d15d176-7930-47b0-ba24-0a69d12fbeee · Cited by 5
Genetics Primer for the General Cardiologist
MacRae, C. A. (2011) · Circulation · doi:10.1161/circulationaha.111.018879 · Cited by 5
Imprinted loci may be more widespread in humans than previously appreciated and enable limited assignment of parental allelic transmissions in unrelated individualsPreprint
Cuéllar-Partida, G., Laurin, C., Ring, S. M., Gaunt, T. R., Relton, C. L., Smith, G. D., & Evans, D. M. (2017) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/161471 · Cited by 5
Phenome-wide analyses identify an association between the parent-of-origin effects dependent methylome and the rate of aging in humans
Gao, C., Amador, C., Walker, R. M., Campbell, A., Madden, R. A., Adams, M. J., Bai, X., Liu, Y., Li, M., Hayward, C., et al. (2023) · Genome biology · doi:10.1186/s13059-023-02953-6 · Cited by 3
SURFBAT: a surrogate family based association test building on large imputation reference panels
Herzig, A. F., Rubinacci, S., Marenne, G., Perdry, H., Génin, E., Campion, D., Dartigues, J., Deleuze, J., Lambert, J., Redon, R., et al. (2024) · G3 Genes Genomes Genetics · doi:10.1093/g3journal/jkae287 · Cited by 4
“2015), and parent-of-origin analyses (Kong et al .”
Diabetes Mellitus
Raffel, L. J., & Goodarzi, M. O. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-383834-6.00090-2 · Cited by 5
Differential relationships between parent-child DXA and pQCT bone measures: Results from the Southampton Women's Survey
Holroyd, C. R., Carter, S., Crozier, S., D’Angelo, S., Curtis, E. M., Moon, R. J., Davies, J. H., Ward, K. A., Dennison, E. M., Inskip, H. M., et al. (2021) · Bone · doi:10.1016/j.bone.2021.116134 · Cited by 4
Incorporating family disease history and controlling case–control imbalance for population-based genetic association studies
Zhuang, Y., Wolford, B. N., Nam, K., Bi, W., Zhou, W., Willer, C. J., Mukherjee, B., & Lee, S. (2022) · Bioinformatics · doi:10.1093/bioinformatics/btac459 · Cited by 4
“For family-based cohorts with partially-missing genotypes, association test power can be improved by using pedigree information (Gudbjartsson et al. , 2008; Kong et al. , 2009; Thornton and McPeek, 2007; Zhong et al. , 2016).”
Role of 19 SNPs in 10 genes with type 2 diabetes in the Pakistani population
Khan, N., Paterson, A. D., Roshandel, D., Maqbool, S., Fazal, N., Ali, L., Khurram, R., Maqsood, S. I., Ali, S. H. B., Khan, H., et al. (2022) · Gene · doi:10.1016/j.gene.2022.146899 · Cited by 4
Large parental differences in chromatin organization in pancreatic beta cell line explaining diabetes susceptibility effects
Jian, X., & Felsenfeld, G. (2021) · Nature Communications · doi:10.1038/s41467-021-24635-2 · Cited by 5
Shedding new light on genetic dark matter
Melhem, N., & Devlin, B. (2010) · Genome Medicine · doi:10.1186/gm200 · Cited by 4
“Genetic variants with parental origin effects, or whose effects depend on the parent from whom they were inherited, could be part of the dark matter; methods are now available to determine the parental origin of alleles and haplotypes even in the absence of genotyped parents [13].”
Background
Adding epigenetics to the mix
Flintoft, L. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2741 · Cited by 4
Understanding human genetic variation in the era of high‐throughput sequencing
Knight, J. C. (2010) · EMBO Reports · doi:10.1038/embor.2010.126 · Cited by 4
“…together with long-range phasing, allows parent-of-origin effects to be defined. the risk associated with t2D for a sequence variant at chromosome 11p15 for example is depen dent on whether the paternal or maternal allele was inherited, and this correlates with DNa methylation (Kong et al, 2009).”
Background
Animal Models of Metabolic Syndrome
Lawson, H. A. (2013) · Elsevier eBooks · doi:10.1016/b978-0-12-415894-8.00011-7 · Cited by 4
Genetic mechanisms of neurodevelopmental disorders
Au, P. Y. B., Eaton, A. J., & Dyment, D. A. (2020) · Handbook of clinical neurology · doi:10.1016/b978-0-444-64150-2.00024-1 · Cited by 5
Dual‐specificity phosphatase 8: A gatekeeper in hypothalamic control of glucose metabolism in males
Kaneko, K., & Katagiri, H. (2021) · Journal of Diabetes Investigation · doi:10.1111/jdi.13561 · Cited by 4
Mapping of Susceptibility Genes for Obesity, Type 2 Diabetes, and the Metabolic Syndrome in Human Populations
Arya, R., Puppala, S., Farook, V. S., Chittoor, G., Jenkinson, C. P., Blangero, J., Hale, D. E., Duggirala, R., & Almasy, L. A. (2015) · Springer eBooks · doi:10.1007/978-3-662-46306-2_12 · Cited by 4
Genetics of Diabetes and Diabetic Complications
Prasad, R. B., Ahlqvist, E., & Groop, L. (2018) · Endocrinology · doi:10.1007/978-3-319-45015-5_6 · Cited by 5
Epigenomics – Impact for Drug Safety Sciences
Lempiäinen, H., Luisier, R., Müller, A., Marc, P., Heard, D. J., Bolognani, F., Moulin, P., Couttet, P., Grenet, O., Marlowe, J. L., et al. (2012) · Wiley eBooks · doi:10.1002/9781118349045.ch19 · Cited by 4
Commentary: Thoughts on assessing evidence for gene by environment interaction
Weinberg, C. R. (2012) · International Journal of Epidemiology · doi:10.1093/ije/dys048 · Cited by 4
Genomic evaluation considering the mosaic genome of the crossbred pig
Sevillano, C. A. (2018) · doi:10.18174/464062 · Cited by 4
Statistical Inference for Propagation Processes on Complex Networks
Manitz, J. (2014) · doi:10.53846/goediss-4597 · Cited by 4
Genetische Studien zum Typ-2-Diabetes
Herder, C. (2010) · Der Diabetologe · doi:10.1007/s11428-009-0500-3 · Cited by 3
DUSP family phosphatases in cell signaling, inflammation, and chronic diseases
Wang, C., Chuang, H., & Tan, T. (2026) · Journal of Biomedical Science · doi:10.1186/s12929-026-01251-0 · Cited by 4
“Human DUSP8 is located near (downstream of) the T2D risk gene rs2334499 identified by GWAS [173, 174].”
Epigenomic Factors in Human Obesity
Bell, C. G. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-388415-2.00014-7 · Cited by 3
Lipid-Associated Variants near ANGPTL3 and LPL Show Parent-of-Origin Specific Effects on Blood Lipid Levels and Obesity
Lessmark, A., Hatem, G., Kovács, G., Vitai, M., Ahlqvist, E., Tuomilehto, J., Koranyi, L. I., Groop, L., & Prasad, R. B. (2021) · Genes · doi:10.3390/genes13010091 · Cited by 3
“An example of this is variants in KCNQ1, which showed an association to T2D in a large scale GWAS but also showed POE in families [28,29].”
Background
All thresholds of maternal hyperglycaemia from the WHO 2013 criteria for gestational diabetes identify women with a higher genetic risk for type 2 diabetes
Hughes, A. E., Hayes, M. G., Egan, A. M., Patel, K. A., Scholtens, D. M., Lowe, L. P., Lowe, W. L., Dunne, F., Hattersley, A. T., & Freathy, R. M. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.16097.1 · Cited by 3
“Median maternal age in years (IQR) 32 (29-36) n=521 35 (31-39)* n=35 34 (31-37)* n=69 32 (29-40) n=16 33 (30-36) n=72”
Association of KLF14 rs4731702 gene polymorphism with metabolic phenotype in young patients with type 1 diabetes
Ryba-Stanisławowska, M. E., Słomiński, B., & Myśliwiec, M. (2024) · Diabetes Obesity and Metabolism · doi:10.1111/dom.15707 · Cited by 3
“25,26 This reasoning is further supported by data showing that both the level of KLF14 and the number of Tregs are reduced in patients with diabetes.”
Influential
Parent-of-origin Effect in Alopecia Areata: A Large-scale Pedigree Study
Redler, S., Basmanav, F. B., Blaumeiser, B., Bartels, N. G., Lutz, G., Tafazzoli, A., Kruse, R., Wolff, H., Böhm, M., Blume‐Peytavi, U., et al. (2017) · Acta Dermato Venereologica · doi:10.2340/00015555-2658 · Cited by 3
All thresholds of maternal hyperglycaemia from the WHO 2013 criteria for gestational diabetes identify women with a higher genetic risk for type 2 diabetes
Hughes, A. E., Hayes, M. G., Egan, A. M., Patel, K., Scholtens, D. M., Lowe, L. P., Lowe, W. L., Dunne, F., Hattersley, A. T., & Freathy, R. M. (2020) · Wellcome Open Research · doi:10.12688/wellcomeopenres.16097.3 · Cited by 4
Cis- and Trans-Effects Underlying Polar Overdominance at the Callipyge Locus
Georges, M., Takeda, H., Cheng, H., Xu, X., Shay, T. L., Cockett, N., & Charlier, C. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8078-5_4 · Cited by 3
Developmental Epigenetic Programming in Diabetes and Obesity
Relton, C. L., Smith, G. D., & Ozanne, S. E. (2013) · Epigenetics and human health · doi:10.1007/978-3-642-36827-1_11 · Cited by 3
TOXPO: TOXicogenomics knowledgebase for inferring toxicity based on POlymorphism
Jo, Y., Koh, I. S., Bae, H., Hong, M., Shin, M., & Kim, Y. S. (2010) · BioChip Journal · doi:10.1007/s13206-010-4202-0 · Cited by 3
Association of the BRCA1 promoter polymorphism rs11655505 with the risk of familial breast and/or ovarian cancer
Bielińska, B., Gaj, P., Kluska, A., Nowakowska, D., Bałabas, A., Dąbrowska, M., Niwińska, A., Gruchota, J., Zub, R., Skasko, E., et al. (2013) · Familial Cancer · doi:10.1007/s10689-013-9647-6 · Cited by 3
“This has been revealed in the study on variants closed in cis- to imprinted genes [24].”
Background
Comparison of Six Statistics of Genetic Association Regarding Their Ability to Discriminate between Causal Variants and Genetically Linked Markers
Bermejo, J. L., García‐Pérez, A., Brandt, A., Hemminki, K., & Matthews, A. G. (2011) · Human Heredity · doi:10.1159/000332006 · Cited by 3
Dissecting prenatal, postnatal, and inherited effects: ART and design
Zhou, J. J., Pelka, S., Lange, K. L., Palmer, C. G. S., & Sinsheimer, J. S. (2011) · Genetic Epidemiology · doi:10.1002/gepi.20591 · Cited by 3
Genetics of Type 2 Diabetes
Florez, J. C., Udler, M. S., & Hanson, R. L. (2021) · Europe PMC (PubMed Central) · Cited by 3
Incorporating information from markers in LD with test locus for detecting imprinting and maternal effects
Zhang, F., & Lin, S. (2020) · European Journal of Human Genetics · doi:10.1038/s41431-020-0590-3 · Cited by 3
Abundant Parent-of-origin Effect eQTL: The Framingham Heart StudyPreprint
Guan, Y., Huan, T., & Levy, D. A. (2024) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2024.06.05.597677 · Cited by 3
“In humans, however, loci with POE in relation to phenotypes are either near imprinted regions by design (Kong et al., 2009; Hanson et al., 2013), or near regions with characteristic of imprinting from a genome-wide scan (Mozaffari et al., 2019).”
Genetic variations and functions of KLF14 in gene expression and metabolic disease development
Riaz, Z., Saeed, S., & Riaz, S. (2025) · Journal of Applied Genetics · doi:10.1007/s13353-025-01015-w · Cited by 2
Genetic variation near GRB10 associated with bone growth and osteosarcoma risk in canine and human populations
Lucas, S. E., Yang, T., Wimberly, C. E., Parmar, K. V., Hansen, H. M., de Smith, A. J., Morimoto, L. M., Metayer, C., Ostrom, Q. T., Eward, W. C., et al. (2024) · Cancer Epidemiology · doi:10.1016/j.canep.2024.102599 · Cited by 3
Transitions in sex determination mechanisms through parental and sexual antagonism
Schenkel, M. A. (2024) · Heredity · doi:10.1038/s41437-024-00717-x · Cited by 2
“A second part lies in the dif ﬁ culty of identifying parentally-antagonistic genes, though examples have been identi ﬁ ed in the context of human disease (Kong et al. 2009) and through parent-of-origin effects on sel ﬁ sh genetic elements (Pliota et al. 2024).”
The Association between the KLF14 rs4731702 SNP and the Lipid Profile in Type 2 Diabetes Mellitus Patients: A Study in San Luis City, San Luis, Argentina
Alvarez, M. F., Gómez, M. E. V., González, I., Fernández, G., & Siewert, S. (2016) · OALib · doi:10.4236/oalib.1103188 · Cited by 2
“All these evidences indicate that this KLF14 variant is an important regulator of lipoprotein metabolism [11].”
BackgroundInfluential
Assessing the Effects of Imprinting and Maternal Genotypes on Complex Genetic Traits
Lin, S. (2013) · Lecture notes in statistics · doi:10.1007/978-1-4614-8981-8_13 · Cited by 2
“Genomic imprinting and maternal genotype effects are two epigenetic factors that modulate the genetic variants’ effects and have been explored increasingly for their role in the etiology of complex traits [30].”
Background
Epigenetic Modifications: Genetic Basis of Environmental Stress Response
Kubota, T., Miyake, K., & Hirasaw, T. (2011) · InTech eBooks · doi:10.5772/20952 · Cited by 2
Conceptual Evolution in Cancer Biology
Zhang, S., Davidson, D. D., & Liang Cheng, C. (2008) · Humana Press eBooks · doi:10.1007/978-1-59745-405-6_7 · Cited by 2
Genes essential for cell viability that are linked to tumor suppressor genes play a role in cancer susceptibility
Wang, Y., Huang, B., Edelmann, L. J., Kolodner, R. D., & Edelmann, W. (2010) · Cell Cycle · doi:10.4161/cc.9.16.12956 · Cited by 2
Discovery and Characterization of Cancer Genetic Susceptibility Alleles
Chanock, S. J., & Ostrander, E. A. (2014) · Elsevier eBooks · doi:10.1016/b978-1-4557-2865-7.00022-9 · Cited by 2
Diabetes
Udler, M. S., & Florez, J. C. (2017) · Elsevier eBooks · doi:10.1016/b978-0-12-800685-6.00014-x · Cited by 2
Dissecting an adiposity locus with an arsenal of genomics
Lorenz, K., & Voight, B. F. (2018) · Genome biology · doi:10.1186/s13059-018-1460-y · Cited by 2
“The T2D- and high-density cholesterol-associated variants in the region are both cis- and trans-expression quantitative trait loci (eQTLs) for KLF14 in adipose [2, 3], making it the leading causal gene candidate.”
Epigenetics in exercise science and sports medicine
Schenk, A., Proschinger, S., & Zimmer, P. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-823928-5.00005-0 · Cited by 2
Potential relationship between single nucleotide polymorphisms used in forensic genetics and diseases or other traits in European population
Pombar‐Gomez, M., López-López, E., Martín‐Guerrero, I., García‐Orad, Á., & de Pancorbo, M. M. (2015) · International Journal of Legal Medicine · doi:10.1007/s00414-015-1165-7 · Cited by 2
“In addition, genetic imprinting is related to several diseases, including diabetes, breast cancer, and obesity, in addition to alcohol dependence [37, 38].”
Designing, Optimization and Validation of Tetra Primer ARMS-PCR Protocol for Genotyping Single Nucleotide Polymorphism rs4731702 (C/T) of KLF14 Gene Associated with Type 2 Diabetes Mellitus: A Study in San Luis, Argentina
Alvarez, M. F., Gómez, M. E. V., & Siewert, S. (2016) · OALib · doi:10.4236/oalib.1103270 · Cited by 3
“Functional studies demonstrate that the maternally transmitted T allele of rs4731702 SNP is associated with increased expression of KLF14 in adipose tissue, indicating the presence of a cis expression quantitative trait loci (eQTL) [10].”
Background
Combinatorial and statistical prediction of gene expression from haplotype sequence
Alpay, B. A., Demetçi, P., Istrail, S., & Aguiar, D. (2020) · Bioinformatics · doi:10.1093/bioinformatics/btaa318 · Cited by 4
Low HDL and High HDL Syndromes
Yamashita, S., & Matsuzawa, Y. (2015) · Elsevier eBooks · doi:10.1016/b978-0-12-801238-3.04000-9 · Cited by 2
Parent-of-Origin inference and its role in the genetic architecture of complex traits: evidence from ∼265,000 individualsPreprint
Hofmeister, R. J., Cavinato, T., Karimi, R., van der Graaf, A., Pajuste, F., Kronberg, J., Taba, N., Mägi, R., Vaudel, M., Rubinacci, S., et al. (2024) · medRxiv · doi:10.1101/2024.12.03.24318392 · Cited by 2
Diabetes Mellitus
Pyeritz, R. E. (2024) · Elsevier eBooks · doi:10.1016/b978-0-12-812531-1.00001-4 · Cited by 1
Genes, Environment and Inheritance
Trent, R. J. (2012) · Elsevier eBooks · doi:10.1016/b978-0-12-381451-7.00002-5 · Cited by 2
Approaches for Dissection of the Genetic Basis of Complex Disease Development in Human
Nicole, J., Bozaoglu, K., Abdul, W., & Jowett, J. B. M. (2012) · InTech eBooks · doi:10.5772/35074 · Cited by 1
“The finding that variants from parental origin are likely to confer increased risk for complex diseases (Kong et al. 2009) supports this approach.”
Background
Genes and Human Obesity
Price, R. A. (2010) · Springer eBooks · doi:10.1007/978-1-4419-1607-5_7 · Cited by 1
Lack of interaction of beta-cell-function-associated variants with hypertension on change in fasting glucose and diabetes risk
de Miguel-Yanes, J. M., Porneala, B., Pencina, M. J., Fox, C. S., Florez, J. C., Siscovick, D. S., Dupuis, J., & Meigs, J. B. (2013) · Journal of Hypertension · doi:10.1097/hjh.0b013e32835f5a83 · Cited by 1
Brain regional thyroid hormone status and Dio3: where genetics, epigenetics and psychiatric vulnerability meet
Sittig, L. J., & Redei, E. E. (2011) · Expert Review of Endocrinology & Metabolism · doi:10.1586/eem.11.64 · Cited by 1
Epigenomic and Noncoding RNA Regulation in Addictive Processes
Satterlee, J. S. (2013) · Epigenetics and human health · doi:10.1007/978-3-642-36827-1_7 · Cited by 1
The Revolution in Genetic Sequencing and Analysis
Pollock, J. D., & Little, A. R. (2015) · Springer eBooks · doi:10.1007/978-1-4614-6434-1_145-1 · Cited by 1
An efficient study design to test parent‐of‐origin effects in family trios
Yu, X., Chen, G., & Feng, R. (2017) · Genetic Epidemiology · doi:10.1002/gepi.22060 · Cited by 1
“To analyze sequence data in families, Kong et al. (2009) used a combination of genealogy and long-range stitching approach to identify parent-of-origins of each genome sequence.”
Method
Genome-wide association study identifies loci influencing concentrations of liver enzymes in plasma
Nmr, S. (2011) · Cited by 1
Genotype Prediction of Adult Type 2 Diabetes From Adolescence in a Multiracial Population
(2012) · PEDIATRICS · doi:10.1542/peds.2012-1132d · Cited by 1
Studying Epigenetics of Cardiovascular Diseases on Chip Guide
Alghamdi, B. A., Al-Johani, I., Alotaibi, B., Ahmed, M. Z., Almazmomi, K., Aloufi, S., & Alshamrani, J. (2022) · Cardiogenetics · doi:10.3390/cardiogenetics12030021 · Cited by 1
Parent-of-origin effects in the life-course evolution of cardiometabolic traits
Wagh, R. S. H., Hatem, G., Andersson, J., Kunte, P. S., Bandyopadhyay, S. K., Yajnik, C. S., & Prasad, R. B. (2025) · Diabetologia · doi:10.1007/s00125-025-06396-5 · Cited by 2
“The rs2237892 SNP at the KCNQ1 locus, the rs4731702 SNP at the KLF14 locus and the rs2334499 SNP at the MOB2 locus have previously been shown to display parent-of-origin effects on type 2 diabetes risk [8, 14, 26].”
Influential
Genetic Predisposition for Type 2 Diabetes Mellitus in a Cameroonian Population: Contribution of rs4731702 (C/T) Polymorphism of Krüppel-Like Factor 14 Gene
Guewo‐Fokeng, M., Sobngwi, E., Atogho‐Tiedeu, B., Lontchi‐Yimagou, E., Chedjou, J.-P., Mbanya, J. C., & Mbacham, W. F. (2021) · Open Journal of Genetics · doi:10.4236/ojgen.2021.112002 · Cited by 2
An Understanding of Diabetes Mellitus Associated Complications, Treatment Modalities and Management Strategies
Paul, N., Pandey, A., & Pandey, K. M. (2019) · Biosciences Biotechnology Research Asia · doi:10.13005/bbra/2737 · Cited by 1
Revolution in Genetics
Pollock, J. D., Lossie, A. C., & Little, A. R. (2022) · Springer eBooks · doi:10.1007/978-3-030-88832-9_145 · Cited by 1
Efficient inference of parent-of-origin effect using case-control mother–child genotype data
Tian, Y., Zhang, H., Bureau, A., Hochner, H., & Chen, J. (2024) · Journal of Statistical Planning and Inference · doi:10.1016/j.jspi.2024.106190 · Cited by 1
The genetics of type 2 diabetes
Ahlqvist, E., & Groop, L. (2015) · Wiley eBooks · doi:10.1002/9781118387658.ch26 · Cited by 1
Restless legs syndrome mothers and attention–deficit/hyperactivity disorder children: What happened between them?
Xiong, L., & Rouleau, G. A. (2010) · Sleep Medicine · doi:10.1016/j.sleep.2010.07.002 · Cited by 1
“, the parent-of-origin genetic effect [15].”
The Role of Genomic Imprints in Placental Biology
Koppes, E. (2016) · D-Scholarship@Pitt (University of Pittsburgh) · Cited by 1
Lifetime Exposure Model of Type 2 DiabetesPreprint
Rončević, A. (2024) · Preprints.org · doi:10.20944/preprints202405.0139.v1
The role of common and rare genetic variation on adiposity across childhoodPreprint
Kentistou, K. A., Sundfjord, J., Karimi, R., Kaisinger, L. R., Hofmeister, R. J., Lupu, A. E., Fragoso-Bargas, N., Zhao, Y., Tadross, J. A., Steuernagel, L., et al. (2025) · medRxiv · doi:10.1101/2025.05.13.25327505 · Cited by 3
“This identified 134 enriched biological pathways ( Supplementary Data 17 ), of which 5 were specifically enriched for Transient BMI associations, 17 for Early-rise, 24 for Late-rise (a further 3 pathways were enriched for 2 trajectories) ( Supplementary Figure 5 ).”
Influential
Expanded map of genomic imprinting reveals insight into human diseasePreprint
Smail, C., Cheung, W., Koseva, B. S., Johnson, A. F., Bi, C., Schreck, C. F., Lydic, M. L., Holoch, K., Repnikova, E. A., Herriges, J. C., et al. (2025) · medRxiv · doi:10.1101/2025.09.15.25335770 · Cited by 1
Genomic Imprinting Effects on Brain and Behavior: Future Directions
Isles, A. R., & Wilkinson, L. S. (2011) · Springer eBooks · doi:10.1007/978-3-642-17426-1_9 · Cited by 1
Interaction Between Genetics and Epigenetics in Cancer
Toland, A. E. (2013) · Springer eBooks · doi:10.1007/978-1-4614-8078-5_9
THE NATURAL AND ORTHOGONAL INTERACTION (NOIA) MODELS FOR QUANTITATIVE TRAITS (QTs) AND COMPLEX DISEASES
Xiao, F. (2013) · Digital Commons-TMC (Texas Medical Center)
Genotype Phasing in Populations of Closely Related Individuals
Hickey, J. M. (2013) · Methods in molecular biology · doi:10.1007/978-1-62703-447-0_16
“Phase information allows the use of analysis frameworks that account for identity by descent (IBD) or parent of origin of allele [2] and it can lead to a large increase in data quantities via genotype or sequence imputation e.”
Background
Heritability of type 2 diabetes and related traits
Lehtovirta, M. (2014) · Työväentutkimus Vuosikirja
Investigation of DNA methylation in type 2 diabetes genetic risk loci
Aðalsteinsson, B. Þ. (2012)
Genomic Imprinting in the Mammalian Brain
Huang, W.-C., & Gregg, C. J. (2013) · Springer eBooks · doi:10.1007/978-4-431-54496-8_12
Recent Progress in Identifying Genes Contributing to Type 2 Diabetes and Metabolic Syndrome
Xie, W., Frayling, T. M., & Weedon, M. N. (2011) · Wiley eBooks · doi:10.1002/9781444347319.ch7
Genome-Wide Association Studies of Human Growth Traits
Weedon, M. N. (2013) · Nestlé Nutrition Institute Workshop series · doi:10.1159/000342541
Bioinformatic and biological analysis of DNA methylation in the human genome
Sigurdsson, M. I. (2011)
Gene and Gene-Set Analysis for Genome-Wide Association StudiesPreprint
Pedroso, I. (2013) · arXiv (Cornell University) · doi:10.48550/arxiv.1308.4102
“This strategy may also incorporate additional information like parent of origin effects, which can be detected in studies using a family design (Kong et al., 2009).”
Background
Investigations of Potential Modifier Genes in Hereditary Haemochromatosis
Brew, J. (2010) · ANU Open Research (Australian National University) · doi:10.25911/5d7a265387fd8
Erratum to: Potential relationship between single nucleotide polymorphisms used in forensic genetics and diseases or other traits in European population
Pombar‐Gomez, M., López-López, E., Martín‐Guerrero, I., García‐Orad, Á., & de Pancorbo, M. M. (2015) · International Journal of Legal Medicine · doi:10.1007/s00414-015-1227-x
“In addition, genetic imprinting is related to several diseases, including diabetes, breast cancer, and obesity, in addition to alcohol dependence [37, 38].”
Nonparametric method for detecting imprinting effect using all members of general pedigrees with missing data
Zhang, F., & Lin, S. (2014) · Journal of Human Genetics · doi:10.1038/jhg.2014.67
Recent Developments in the Genetic and Genomic Basis of Type 2 Diabetes
Richards, H. B., & McCarthy, M. I. (2012) · Current Cardiovascular Risk Reports · doi:10.1007/s12170-012-0281-x
Kernel Methods for Genes and Networks to Study Genome-Wide Associations of Lung Cancer and Rheumatoid Arthritis
Freytag, S. (2014) · doi:10.53846/goediss-4373

Authors: DIAGRAM Consortium, Kong, A., Steinthorsdottir, V., Masson, G., Thorleifsson, G., Sulem, P., Besenbacher, S., Jonasdottir, A., Sigurdsson, A., Kristinsson, K. T., Jonasdottir, A., Frigge, M. L., Gylfason, A., Olason, P. I., Gudjonsson, S. A., Sverrisson, S., Stacey, S. N., Sigurgeirsson, B., Benediktsdottir, K. R., Sigurdsson, H., Jonsson, T., Benediktsson, R., Olafsson, J. H., Johannsson, O. T., Hreidarsson, A. B., Sigurdsson, G., Ferguson-Smith, A. C., Gudbjartsson, D. F., Thorsteinsdottir, U., & Stefansson, K.
Affiliations: deCODE Genetics (Iceland) (IS)
National University Hospital of Iceland (IS)
Corresponding author: Kong, Augustine
ORCID: Kong, Augustine
Sulem, Patrick
Frigge, Michael L.
Gylfason, Arnaldur
Olason, Pall I.
Gudjonsson, Sigurjon A.
Stacey, Simon N.
Benediktsson, Rafn
Gudbjartsson, Daniel F.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2009-12
Volume: 462
Issue: 7275
Pages: 868-874
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature08625
PMC: PMC3746295
OpenAlex: W2156431476
Cited by: 553
References: 23
Citations by year: 2026: 3 · 2025: 12 · 2024: 16 · 2023: 8 · 2022: 18 · 2021: 24 · 2020: 24 · 2019: 22 · 2018: 28 · 2017: 32 · 2016: 32 · 2015: 55 · 2014: 43 · 2013: 57 · 2012: 49
FWCI: 34.22
Type: journal article
Language: en
Open access: green
europepmc.org
Licence: www.springer.com/tdm (tdm)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
Research Explorer (The University of Manchester) (publishedVersion)
Europe PMC (PubMed Central) (acceptedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Site cant be reached (submittedVersion)
Edinburgh Research Explorer (University of Edinburgh) (submittedVersion, other-oa)
Open Research (University of Surrey) (submittedVersion)
Hirsla (Landspítali University Hospital) (submittedVersion, other-oa)
Newcastle University ePrints (Newcastle Univesity)
Funders: Wellcome Trust (077016, 090532)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK029867)
National Institute of Arthritis and Musculoskeletal and Skin Diseases (K08AR055688)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and phenotypic traits in livestock
Keywords: parental origin, genomic imprinting, imprinted genes, genetic variants, type 2 diabetes, breast cancer, basal cell carcinoma, 11p15, CTCF binding sites, DNA methylation, genealogy, TCF7L2, complex diseases
MeSH terms: CCCTC-Binding Factor, Alleles, Binding Sites, Breast Neoplasms, Basal Cell Carcinoma, Chromosomes, Human, Pair 11, Chromosomes, Human, Pair 7, Diabetes Mellitus, Type 2, Fathers, Female, Haplotypes, Humans, Iceland, Male, Mothers, Pedigree, Repressor Proteins, Genome, Human, Genomic Imprinting, DNA Methylation, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide

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

Parental origin of sequence variants associated with complex diseases

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks