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 accessAbstract
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.
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.
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?
In the citing paper
“It is now widely believed that many genetic and epigenetic factors are likely to contribute to common complex diseases, including multiple rare SNVs (defined by convention as those that have frequencies < 1%), copy number variations (CNVs), and other forms of structural variation. 3–12”
From Statistical analysis strategies for association studies involving rare variants (2010) · cites this paper as [6]
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
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-citationAnalysis 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
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
Flagged first, then by citations
Cited by
Sorted by citations
Items 101–200 of 552
GWAS in autoimmune thyroid disease: redefining our understanding of pathogenesis
Simmonds, M. J. (2013) · Nature Reviews Endocrinology · doi:10.1038/nrendo.2013.56 · Cited by 132
Recent advances in the molecular genetics of type 2 diabetes mellitus
Brunetti, A., CHIEFARI, E. D., & FOTI, D. P. (2014) · World Journal of Diabetes · doi:10.4239/wjd.v5.i2.128 · Cited by 137
Genetics and Genomics for the Prevention and Treatment of Cardiovascular Disease: Update
Ganesh, S. K., Arnett, D. K., Assimes, T. L., Basson, C. T., Chakravarti, A., Ellinor, P. T., Engler, M. B., Goldmuntz, E., Herrington, D. M., Hershberger, R. E., et al. (2013) · Circulation · doi:10.1161/01.cir.0000437913.98912.1d · Cited by 130
Insights into imprinting from parent-of-origin phased methylomes and transcriptomes
Zink, F., Magnúsdóttir, D. N., Magnússon, Ó. Þ., Walker, N. J., Morris, T. J., Sigurðsson, Á., Halldorsson, G. H., Gudjonsson, S. A., Melsted, P., Ingimundardóttir, H., et al. (2018) · Nature Genetics · doi:10.1038/s41588-018-0232-7 · Cited by 123
Self-citationStudying the epigenome using next generation sequencing
Ku, C., Naidoo, N., Wu, M., & Soong, R. (2011) · Journal of Medical Genetics · doi:10.1136/jmedgenet-2011-100242 · Cited by 127
“68 An SNP association in the imprinted region of chromosome 14q32.”
Transient neonatal diabetes mellitus type 1
Mackay, D., & Temple, I. K. (2010) · American Journal of Medical Genetics Part C Seminars in Medical Genetics · doi:10.1002/ajmg.c.30272 · Cited by 129
Child Development and Molecular Genetics: 14 Years Later
Plomin, R. J. (2012) · Child Development · doi:10.1111/j.1467-8624.2012.01757.x · Cited by 125
“Moreover, some SNP associations have been shown to be moderated by parent-of-origin effects resulting in stronger associations with one parent or the other (Kong et al., 2009).”
BackgroundRecent advances in understanding the genetic architecture of type 2 diabetes
Mohlke, K. L., & Boehnke, M. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv264 · Cited by 124
“An Icelandic study was first to report that variants located near KCNQ1, MOB2 and KLF14 showed stronger evidence of association when maternally inherited than when paternally inherited (59).”
BackgroundBrown, W. M. (2015) · British Journal of Sports Medicine · doi:10.1136/bjsports-2014-094073 · Cited by 100
Genome-wide association studies and type 2 diabetes
Wheeler, E., & Barroso, I. (2011) · Briefings in Functional Genomics · doi:10.1093/bfgp/elr008 · Cited by 119
Travers, M. E., Mackay, D. J. G., Dekker Nitert, M., Morris, A. P., Lindgren, C. M., Berry, A., Johnson, P. R., Hanley, N., Groop, L. C., McCarthy, M. I., et al. (2013) · Diabetes · doi:10.2337/db12-0819 · Cited by 118
Whole genome characterization of sequence diversity of 15,220 Icelanders
Jónsson, H., Sulem, P., Kehr, B., Kristmundsdóttir, S., Zink, F., Hjartarson, E., Hardarson, M. T., Hjörleifsson, K. E., Eggertsson, H. P., Gudjonsson, S. A., et al. (2017) · Scientific Data · doi:10.1038/sdata.2017.115 · Cited by 118
“Finally, we long range phased (LRP) the data set using the algorithm described by Kong et al.(9), resulting in a panel of 151,677 individuals with LRP chip genotypes.”
MethodSelf-citationGenetics of impulsive behaviour
Bevilacqua, L. M., & Goldman, D. A. (2013) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2012.0380 · Cited by 129
“It is also possible that parental-origin-specific associations may be important [128].”
BackgroundHaraldsdóttir, S., Rafnar, Þ., Frankel, W. L., Einarsdottir, S., Sigurðsson, Á., Hampel, H., Snæbjörnsson, P., Másson, G., Weng, D. Y., Arngrı́msson, R., et al. (2017) · Nature Communications · doi:10.1038/ncomms14755 · Cited by 117
Self-citationAn integrated epigenomic analysis for type 2 diabetes susceptibility loci in monozygotic twins
Yuan, W., Xia, Y., Bell, C. G., Yet, İ., Ferreira, T. C., Ward, K. J., Gao, F., Loomis, A. K., Hyde, C. L., Wu, H., et al. (2014) · Nature Communications · doi:10.1038/ncomms6719 · Cited by 117
Genome-Wide Association Study of Relative Telomere Length
Prescott, J., Kraft, P. L., Chasman, D. I., Savage, S. A., Mirabello, L. J., Berndt, S. I., Weissfeld, J. L., Han, J., Hayes, R. B., Chanock, S. J., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0019635 · Cited by 112
“associations reduced [69].”
Freathy, R. M., Hayes, M. G., Urbanek, M., Lowe, L. P., Lee, H., Ackerman, C. M., Frayling, T. M., Cox, N. J., Dunger, D. B., Dyer, A. R., et al. (2010) · Diabetes · doi:10.2337/db10-0177 · Cited by 105
Advanced research on risk factors of type 2 diabetes
Bi, Y., Wang, T., Xu, M., Xu, Y., Li, M., Lu, J., Zhu, X., & Ning, G. (2012) · Diabetes/Metabolism Research and Reviews · doi:10.1002/dmrr.2352 · Cited by 110
Molecular Basis of Obesity: Current Status and Future Prospects
Choquet, H., & Meyre, D. (2011) · Current Genomics · doi:10.2174/138920211795677921 · Cited by 106
“Beyond the study of BMI, four GWAS have investigated the genetic architecture of body fat distribution, estimated by waist circumference (WC) or waist to hip ratio (WHR) measurements [110-113].”
BackgroundType 2 diabetes, glucose, insulin, BMI, and ischemic stroke subtypes
Larsson, S. C., Scott, R. A., Traylor, M., Langenberg, C., Hindy, G., Melander, O., Orho‐Melander, M., Seshadri, S. S., Wareham, N. J., & Markus, H. S. (2017) · Neurology · doi:10.1212/wnl.0000000000004173 · Cited by 109
Height-reducing variants and selection for short stature in Sardinia
Żołędziewska, M., The Understanding Society Scientific Group, Sidore, C., Chiang, C. W. K., Sanna, S., Mulas, A., Steri, M., Busonero, F., Marcus, J. H., Marongiu, M., et al. (2015) · Nature Genetics · doi:10.1038/ng.3403 · Cited by 100
Genetic effects on the timing of parturition and links to fetal birth weight
Solé-Navais, P., Flatley, C. J., Steinthórsdóttir, V., Vaudel, M., Juodakis, J., Chen, J., Laisk, T., LaBella, A. L., Westergaard, D., Bačelis, J., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01343-9 · Cited by 105
Self-citationStyrkársdóttir, U., Helgason, H., Sigurðsson, Á., Norddahl, G. L., Agustsdottir, A. B., Reynard, L. N., Villalvilla, A., Halldorsson, G. H., Jónasdóttir, Á., Magnusdottir, A., et al. (2017) · Nature Genetics · doi:10.1038/ng.3816 · Cited by 103
Self-citationBoesgaard, T. W., Grarup, N., Jørgensen, T., Borch‐Johnsen, K., Hansen, T. F., & Pedersen, O. B. (2010) · Diabetologia · doi:10.1007/s00125-010-1753-5 · Cited by 99
“So far, genome-wide association studies (GWAS) and subsequent meta-analysis have identified 23 validated risk loci influencing risk of type 2 diabetes [1–3].”
BackgroundKu, C., Polychronakos, C., Tan, E., Naidoo, N., Yudi Pawitan, Y., Roukos, D. H., Mort, M. E., & Cooper, D. N. (2012) · Molecular Psychiatry · doi:10.1038/mp.2012.58 · Cited by 99
Perhexiline activates KLF14 and reduces atherosclerosis by modulating ApoA-I production
Guo, Y., Fan, Y., Zhang, J., Lomberk, G. A., Zhou, Z., Sun, L., Mathison, A., Garcia-Barrio, M. T., Zhang, J., Zeng, L., et al. (2015) · Journal of Clinical Investigation · doi:10.1172/jci79048 · Cited by 97
“Among those genes identified by GWAS, the T allele of rs4731702, located near the KLF14 gene, is significantly associated with HDL-C levels and a decreased risk of CHD and type 2 diabetes (17, 18, 50).”
BackgroundCompletely phased genome sequencing through chromosome sorting
Yang, H., Chen, X., & Wong, W. H. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1016725108 · Cited by 95
HDL Cholesterol Metabolism and the Risk of CHD: New Insights from Human Genetics
Vitali, C., Khetarpal, S. A., & Rader, D. J. (2017) · Current Cardiology Reports · doi:10.1007/s11886-017-0940-0 · Cited by 96
Distinction between the effects of parental and fetal genomes on fetal growth
Juliusdottir, T., Steinthórsdóttir, V., Stefánsdóttir, L., Sveinbjörnsson, G., Ivarsdottir, E. V., Þórólfsdóttir, R. B., Sigurdsson, J. K., Tragante, V., Hjörleifsson, K. E., Helgadóttir, A., et al. (2021) · Nature Genetics · doi:10.1038/s41588-021-00896-x · Cited by 94
Self-citationThe Architecture of Parent-of-Origin Effects in Mice
Mott, R., Wei, Y., Kaisaki, P. J., Gan, X., Cleak, J., Edwards, A., Baud, A., & Flint, J. (2014) · Cell · doi:10.1016/j.cell.2013.11.043 · Cited by 97
“In one human population in which this has been 332 Cell 156, 332–342, January 16, 2014 ª2014 The Authors possible (Iceland), it has emerged as a potentially important contributor to human genetic disease (Kong et al., 2009).”
BackgroundChildhood Bone Mineral Content Is Associated With Methylation Status of the RXRA Promoter at Birth
Harvey, N. C., Sheppard, A. M., Godfrey, K. M., McLean, C., Garratt, E. S., Ntani, G., Davies, L. C., Murray, R. J. S., Inskip, H. M., Gluckman, P. D., et al. (2013) · Journal of Bone and Mineral Research · doi:10.1002/jbmr.2056 · Cited by 91
Sigurðsson, S., Alexandersson, K. F., Sulem, P., Feenstra, B., Guðmundsdóttir, S., Halldorsson, G. H., Ólafsson, S., Sigurðsson, Á., Rafnar, Þ., Thorgeirsson, T. E., et al. (2017) · Nature Communications · doi:10.1038/ncomms15789 · Cited by 91
“The sequence variants were imputed into 294,212 untyped relatives of the chip - typed individuals to further increase the sample size for association analysis and increase the power to detect associations 10,11,41 .”
Self-citationDNA Nanomaterial-Based Electrochemical Biosensors for Clinical Diagnosis
Chu, M., Zhang, Y., Ji, C., Zhang, Y., Yuan, Q., & Tan, J. (2024) · ACS Nano · doi:10.1021/acsnano.4c11857 · Cited by 90
A rare missense mutation in MYH6 associates with non-syndromic coarctation of the aorta
Björnsson, Þ., Þórólfsdóttir, R. B., Sveinbjörnsson, G., Sulem, P., Norddahl, G. L., Helgadóttir, A., Grétarsdóttir, S., Magnusdottir, A., Daníelsen, R., Sigurdsson, E. L., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy142 · Cited by 86
“The sequence variants identified in the 15 220 sequenced Icelanders were then imputed into 151 677 Icelanders who had been genotyped with various Illumina single nucleotide polymorphism chips and their genotypes phased using long-range phasing.(19,20) The imputation of the sequence variants, identified thorough wholeg…”
MethodSelf-citationTackling the epigenome: challenges and opportunities for collaboration
Satterlee, J. S., Schübeler, D., & Ng, H. (2010) · Nature Biotechnology · doi:10.1038/nbt1010-1039 · Cited by 84
Characterization of the genetic architecture of infant and early childhood body mass index
Helgeland, Ø., Vaudel, M., Solé-Navais, P., Flatley, C. J., Juodakis, J., Bačelis, J., Koløen, I. L., Knudsen, G. P., Johansson, B. B., Magnus, P. M., et al. (2022) · Nature Metabolism · doi:10.1038/s42255-022-00549-1 · Cited by 79
Hoggart, C. J., Venturini, G., Mangino, M., Gomez, F., Ascari, G., Zhao, J. H., Teumer, A., Winkler, T. W., Tšernikova, N., Luan, J., et al. (2014) · PLoS Genetics · doi:10.1371/journal.pgen.1004508 · Cited by 80
“A notable exception is the work of Kong et al [1] who inferred parental origin through genealogy information and long-range phasing to subsequently test for POEs.”
Raulerson, C. K., Ko, A., Kidd, J., Currin, K. W., Brotman, S. M., Cannon, M. E., Wu, Y., Spracklen, C. N., Jackson, A., Stringham, H. M., et al. (2019) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2019.09.001 · Cited by 75
Antó, J. M., Pinart, M., Akdiş, M., Auffray, C., Bachert, C., Basagaña, X., Carlsen, K., Guerra, S., von Hertzen, L., Illi, S., et al. (2012) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2012.01.047 · Cited by 82
Molecular mechanisms of genomic imprinting and clinical implications for cancer
Uribe‐Lewis, S., Woodfine, K., Stojic, L., & Murrell, A. (2011) · Expert Reviews in Molecular Medicine · doi:10.1017/s1462399410001717 · Cited by 79
Advanced paternal and grandpaternal age and schizophrenia: A three-generation perspective
Frans, E. M., McGrath, J. J., Sandin, S., Lichtenstein, P., Reichenberg, A., Långström, N., & Hultman, C. M. (2011) · Schizophrenia Research · doi:10.1016/j.schres.2011.09.027 · Cited by 77
“There is also evidence that candidate single nucleotide polymorphisms (SNPs) within known imprinted regions of the genome can be either protective or harmful for disease outcomes depending on the parent of origin of the variant (Kong et al., 2009) (Kong et al., 2009).”
BackgroundGenetic and epigenetic sex-specific adaptations to endurance exercise
Landen, S., Voisin, S., Craig, J. M., McGee, S. L., Lamon, S., & Eynon, N. (2019) · Epigenetics · doi:10.1080/15592294.2019.1603961 · Cited by 76
“[106] Kong A, Steinthorsdottir V, Masson G, et al.”
BackgroundConsanguineous Marriage and Human Evolution
Bittles, A. H., & Black, M. L. (2010) · Annual Review of Anthropology · doi:10.1146/annurev.anthro.012809.105051 · Cited by 84
New basal cell carcinoma susceptibility loci
Stacey, S., Helgason, H., Gudjonsson, S. A., Þorleifsson, G., Zink, F., Sigurðsson, Á., Kehr, B., Guðmundsson, J., Sulem, P., Sigurgeirsson, B., et al. (2015) · Nature Communications · doi:10.1038/ncomms7825 · Cited by 73
Self-citationHelgadóttir, A., Sulem, P., Þorgeirsson, G., Grétarsdóttir, S., Þorleifsson, G., Jensson, B. Ö., Arnadottir, G. A., Ólafsson, Í., Eyjolfsson, G. I., Sigurðardóttir, Ó., et al. (2018) · European Heart Journal · doi:10.1093/eurheartj/ehy169 · Cited by 74
Self-citationBeaumont, R. N., Flatley, C. J., Vaudel, M., Wu, X., Chen, J., Moen, G.-H., Skotte, L., Helgeland, Ø., Solé-Navais, P., Banasik, K., et al. (2023) · Nature Genetics · doi:10.1038/s41588-023-01520-w · Cited by 73
“This variant shows POE on type 2 diabetes risk 26 , where the maternally inherited risk allele (C) corresponds to the maternally inherited PW-decreasing allele identified here.”
BackgroundThe virtuous cycle of human genetics and mouse models in drug discovery
Nadeau, J. H., & Auwerx, J. H. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-018-0009-9 · Cited by 78
Ancestral paternal genotype controls body weight and food intake for multiple generations
Yazbek, S. N., Spiezio, S. H., Nadeau, J. H., & Buchner, D. A. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq332 · Cited by 73
“Although considerably less information is available for humans owing to experimental difficulties, two recent GWASs found regions of the genome that control susceptibility to cancer and type 1 and 2 diabetes in a parent-of-origin-dependent manner (29,30).”
BackgroundA Genome-Wide Association Study Confirms Previously Reported Loci for Type 2 Diabetes in Han Chinese
Cui, B., Zhu, X., Xu, M., Guo, T., Zhu, D., Chen, G., Li, X., Xu, L., Bi, Y., Chen, Y., et al. (2011) · PLoS ONE · doi:10.1371/journal.pone.0022353 · Cited by 72
“More recently, several genome-wide association studies (GWASs) have been completed in independent population samples derived from Caucasians and Japanese, and identified a host of novel susceptibility loci of T2D [8–19].”
BackgroundStyrkársdóttir, U., Þorleifsson, G., Gudjonsson, S. A., Sigurðsson, Á., Lee, S. H., Nguyen, T. V., Kwok, T. C. Y., Lee, J. S. W., Ho, S. C., Woo, J., et al. (2016) · Nature Communications · doi:10.1038/ncomms10129 · Cited by 72
Self-citationGenetic Determinants for Gestational Diabetes Mellitus and Related Metabolic Traits in Mexican Women
Huerta-Chagoya, A., Vázquez-Cárdenas, P., Moreno-Macías, H., Tapia-Maruri, L., Rodríguez-Guillén, R., López-Vite, E., García-Escalante, G., Escobedo-Aguirre, F., Parra-Covarrubias, A., Cordero-Brieño, R., et al. (2015) · PLOS ONE · doi:10.1371/journal.pone.0126408 · Cited by 72
Hereditary breast cancer: ever more pieces to the polygenic puzzle
Bogdanova, N. V., Helbig, S., & Dörk, T. (2013) · Hereditary Cancer in Clinical Practice · doi:10.1186/1897-4287-11-12 · Cited by 72
“11p15 rs3817198, rs909116 LSP1-TNNT3 CTSD, DUSP8, IGF2 ER + ve ~ ER-ve [95,101,128]”
Predicting Stroke Through Genetic Risk Functions
Ibrahim‐Verbaas, C. A., Fornage, M., Bis, J. C., Choi, S. H., Psaty, B. M., Meigs, J. B., Rao, M., Nalls, M. A., Fontes, J. D., O’Donnell, C. J., et al. (2014) · Stroke · doi:10.1161/strokeaha.113.003044 · Cited by 71
Hanson, R. L., Guo, T., Muller, Y. L., Fleming, J., Knowler, W. C., Kobes, S., Bogardus, C., & Baier, L. J. (2013) · Diabetes · doi:10.2337/db12-1767 · Cited by 73
RNA as the substrate for epigenome‐environment interactions
Mattick, J. S. (2010) · BioEssays · doi:10.1002/bies.201000028 · Cited by 67
Neonatal Cytokine Profile in the Airway Mucosal Lining Fluid Is Skewed by Maternal Atopy
Følsgaard, N. V., Chawes, B., Rasmussen, M. A., Bischoff, A. L., Carson, C. G., Stokholm, J., Pedersen, L., Hansel, T. T., Bønnelykke, K., Brix, S., et al. (2011) · American Journal of Respiratory and Critical Care Medicine · doi:10.1164/rccm.201108-1471oc · Cited by 69
Genetics of coronary artery disease: Genome-wide association studies and beyond
Prins, B. P., Lagou, V., Asselbergs, F. W., Snieder, H., & Fu, J. (2012) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2012.05.015 · Cited by 69
“Several studies have argued that epigenetic variation is a driving force of development, evolutionary adaption, and complex diseases [62,63].”
BackgroundQuantitative Epigenetics Through Epigenomic Perturbation of Isogenic Lines
Johannes, F. M., & Colomé‐Tatché, M. (2011) · Genetics · doi:10.1534/genetics.111.127118 · Cited by 66
“A recent study by Kong et al. (2009), for example, illustrates that knowledge of the epigenetic status of sequence alleles (in this case, the parent-of-origin of the alleles) is often necessary to establish significant associations with phenotypes.”
BackgroundGuilmatre, A., & Sharp, A. (2011) · Clinical Genetics · doi:10.1111/j.1399-0004.2011.01790.x · Cited by 64
“(25) were able to assess the effect of parental origin on disease risk for three common conditions.”
BackgroundGenome-wide assessment of imprinted expression in human cells
Morcos, L., Ge, B., Koka, V., Lam, K. C. L., Pokholok, D., Gunderson, K. L., Montpetit, A., Verlaan, D. J., & Pastinen, T. (2011) · Genome biology · doi:10.1186/gb-2011-12-3-r25 · Cited by 66
“Recent evidence suggests that common disease, such as basal-cell carcinoma and type 2 diabetes, can also be impacted by parent-of-originspecific allelic variants [2].”
BackgroundSequence variants from whole genome sequencing a large group of Icelanders
Gudbjartsson, D. F., Sulem, P., Helgason, H., Gylfason, A., Gudjonsson, S. A., Zink, F., Oddsson, Á., Magnusson, G., Halldórsson, B. V., Hjartarson, E., et al. (2015) · Scientific Data · doi:10.1038/sdata.2015.11 · Cited by 67
Self-citationGenetic architecture of type 2 diabetes
Hara, K., Shojima, N., Hosoe, J., & Kadowaki, T. (2014) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2014.08.012 · Cited by 69
The epigenomic interface between genome and environment in common complex diseases
Bell, C. G., & Beck, S. (2010) · Briefings in Functional Genomics · doi:10.1093/bfgp/elq026 · Cited by 64
“In an Icelandic cohort, this analysis found breast cancer, basal-cell carcinoma and type 2 diabetes (T2D) SNP associations [61], with one of the latter showing a differentially methylated CTCF-binding site and decreased methylation.”
Maternal Modifiers and Parent-of-Origin Bias of the Autism-Associated 16p11.2 CNV
Duyzend, M., Nuttle, X., Coe, B. P., Baker, C. A., Nickerson, D. A., Bernier, R., & Eichler, E. E. (2015) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2015.11.017 · Cited by 65
The correlation between CpG methylation and gene expression is driven by sequence variants
Stefánsson, Ó. A., Sigurpalsdottir, B. D., Rögnvaldsson, S., Halldorsson, G. H., Juliusson, K., Sveinbjörnsson, G., Gunnarsson, B., Beyter, D., Jónsson, H., Gudjonsson, S. A., et al. (2024) · Nature Genetics · doi:10.1038/s41588-024-01851-2 · Cited by 74
“The diploid haplotype reference was created for each individual and long-range phased haplotype 57 .”
Self-citationNakabayashi, K., Trujillo, A. M., Tayama, C., Camprubí, C., Yoshida, W., Lapunzina, P. D., Sánchez, A., Soejima, H., Aburatani, H., Nagae, G., et al. (2011) · Human Molecular Genetics · doi:10.1093/hmg/ddr224 · Cited by 63
Genes Contributing to Genetic Variation of Muscling in Sheep
Tellam, R. L., Cockett, N., Vuocolo, T., & Bidwell, C. A. (2012) · Frontiers in Genetics · doi:10.3389/fgene.2012.00164 · Cited by 68
Human imprinting disorders: Principles, practice, problems and progress
Mackay, D., & Temple, I. K. (2017) · European Journal of Medical Genetics · doi:10.1016/j.ejmg.2017.08.014 · Cited by 66
Synthetic associations in the context of genome-wide association scan signals
Orozco, G., Barrett, J. C., & Zeggini, E. (2010) · Human Molecular Genetics · doi:10.1093/hmg/ddq368 · Cited by 61
“Complex patterns of inheritance, such as parent of origin effects (32), as well as inherited epigenetic modifications of the genome, the presence of phenotype heterogeneity in the cohorts used in the first wave of GWAS, or even an initial over-estimation of the heritability of complex traits (33) can also contribute t…”
BackgroundAdaptive Evolution and the Birth of CTCF Binding Sites in the Drosophila Genome
Ni, X., Zhang, Y. E., Nègre, N., Chen, S., Long, M., & White, K. P. (2012) · PLoS Biology · doi:10.1371/journal.pbio.1001420 · Cited by 62
“In vertebrates, this 11 zinc-finger protein is shown to be crucial in processes of epigenetic imprinting [26,27], X chromosome inactivation [28], and associated with various complex human diseases including cancer and diabetes [29–31].”
BackgroundMolecular factors involved in the development of diabetic foot syndrome.
Bruhn‐Olszewska, B., Korzon-Burakowska, A., Gabig‐Cimińska, M., Olszewski, P., Węgrzyn, A., & Jakóbkiewicz‐Banecka, J. (2012) · Acta Biochimica Polonica · doi:10.18388/abp.2012_2085 · Cited by 63
Asahara, S.-I., Etoh, H., Inoue, H., Teruyama, K., Shibutani, Y., Ihara, Y., Kawada, Y., Bartolome, A., Hashimoto, N., Matsuda, T., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1422104112 · Cited by 63
“SNPs of KCNQ1 have been associated with diabetes mellitus in the Icelandic population in a manner dependent on parental origin (11).”
BackgroundPierce, B. L., Austin, M. A., & Ahsan, H. (2011) · Cancer Causes & Control · doi:10.1007/s10552-011-9760-5 · Cited by 60
“For example, there are known parent-of-origin effects for H19/IFG2 SNP rs2334499 and KCNQ1 SNPs rs2237892 and rs231362 (no adequate tagSNP) [41], however, we did not account for these effects in this analysis, as we have no available data on maternal/paternal transmission.”
ResultA protein-truncating R179X variant in RNF186 confers protection against ulcerative colitis
Rivas, M. A., Graham, D. B., Sulem, P., Stevens, C. R., Desch, A. N., Goyette, P., Gudbjartsson, D. F., Jónsdóttir, I., Þorsteinsdóttir, U., Degenhardt, F. C., et al. (2016) · Nature Communications · doi:10.1038/ncomms12342 · Cited by 59
Self-citationNext Steps in Cardiovascular Disease Genomic Research—Sequencing, Epigenetics, and Transcriptomics
Schnabel, R. B., Baccarelli, A., Lin, H., Ellinor, P. T., & Benjamin, E. J. (2011) · Clinical Chemistry · doi:10.1373/clinchem.2011.170423 · Cited by 58
“At a population level, a differentially methylated CTCF-binding site at 11p15 was discovered in relation to type 2 diabetes(50).”
BackgroundTransgenerational Genetic Effects
Nelson, V. R., & Nadeau, J. H. (2010) · Epigenomics · doi:10.2217/epi.10.57 · Cited by 58
Epigenetic and genetic components of height regulation
Benónísdóttir, S., Oddsson, Á., Helgason, A., Kristjansson, R. P., Sveinbjörnsson, G., Óskarsdóttir, A., Þorleifsson, G., Davidsson, O. B., Arnadottir, G. A., Sulem, G., et al. (2016) · Nature Communications · doi:10.1038/ncomms13490 · Cited by 63
“…Long-range phasing of haplotypes using surrogate parents allows for accurate phasing of Icelandic samples and the Icelandic genealogy coupled with the large fraction of chip-typed individuals in the population enabled the determination of the parent-of-origin for the genotypes (refs 6,14).”
InfluentialSelf-citationKaraderi, T., Drong, A., & Lindgren, C. M. (2015) · Current Diabetes Reports · doi:10.1007/s11892-015-0648-8 · Cited by 57
Sex‐specific plasticity across generations I: Maternal and paternal effects on sons and daughters
Hellmann, J. K., Bukhari, S. A., Deno, J., & Bell, A. M. (2020) · Journal of Animal Ecology · doi:10.1111/1365-2656.13364 · Cited by 59
“Both distinct and interactive effects could also be mediated by epigenetic mechanisms such as parent-of-origin effects (Kong et al., 2009; Lawson et al., 2013) or interactions between maternal and paternal contributions (e.g. egg cytoplasm altering the effect of sperm small RNAs) during early…”
BackgroundHeterozygote carriers for CNVs inPARK2are at increased risk of Parkinson's disease
Huttenlocher, J., Stefánsson, H., Steinberg, S., Helgadottir, H. T., Sveinbjörnsdóttir, S., Rieß, O., Bauer, P. O., & Stefánsson, K. (2015) · Human Molecular Genetics · doi:10.1093/hmg/ddv277 · Cited by 57
Common and specific liability to addiction: Approaches to association studies of opioid addiction
Nielsen, D. A., & Kreek, M. J. (2012) · Drug and Alcohol Dependence · doi:10.1016/j.drugalcdep.2012.03.026 · Cited by 55
Age-related hearing loss pertaining to potassium ion channels in the cochlea and auditory pathway
Pinheiro, B. P., Vona, B., Löwenheim, H., Rüttiger, L., Knipper, M., & Adel, Y. (2020) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-020-02496-w · Cited by 56
Genetics of Type 2 Diabetes in East Asian Populations
Cho, Y. S., Lee, J., Park, K. S., & Nho, C. W. (2012) · Current Diabetes Reports · doi:10.1007/s11892-012-0326-z · Cited by 57
Halmøy, A., Johansson, S., Winge, I., McKinney, J. A., Knappskog, P. M., & Haavik, J. (2010) · Archives of General Psychiatry · doi:10.1001/archgenpsychiatry.2010.124 · Cited by 59
Insights into the genetic basis of type 2 diabetes
Kato, N. (2013) · Journal of Diabetes Investigation · doi:10.1111/jdi.12067 · Cited by 58
“As an approach to addressing this issue, Kong et al.51 examined the impact of parental origin on disease associations in previous GWA studies and identified parental-origin-specific associations with type 2 diabetes at variants located in the known imprinted region on chromosome 11p15.”
MethodGenome-wide association study yields variants at 20p12.2 that associate with urinary bladder cancer
Rafnar, Þ., Sulem, P., Þorleifsson, G., Vermeulen, S. H. H. M., Helgason, H., Saemundsdottir, J., Gudjonsson, S. A., Sigurðsson, Á., Stacey, S., Guðmundsson, J., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddu264 · Cited by 54
“Of the Icelandic subjects, 826 cases and 44 604 controls were directly genotyped, the remaining cases and controls are individuals that had not been chip typed, but for which genotype probabilities were imputed using methods of familial imputation (17).”
Self-citationEvidence for germline non-genetic inheritance of human phenotypes and diseases
Senaldi, L., & Smith-Raska, M. (2020) · Clinical Epigenetics · doi:10.1186/s13148-020-00929-y · Cited by 61
“In this study, a parent-of-origin association was discovered between specific SNPs and breast cancer, basal cell carcinoma, and type II diabetes [83].”
BackgroundGermline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma
Stacey, S., Sulem, P., Gudbjartsson, D. F., Jónasdóttir, Á., Þorleifsson, G., Gudjonsson, S. A., Másson, G., Guðmundsson, J., Sigurgeirsson, B., Benediktsdóttir, K. R., et al. (2014) · Human Molecular Genetics · doi:10.1093/hmg/ddt671 · Cited by 53
Self-citationType 2 Diabetes-Associated Genetic Polymorphisms as Potential Disease Predictors
Witka, B. Z., Oktaviani, D. J., Marcellino, M., Barliana, M. I., & Abdulah, R. (2019) · Diabetes Metabolic Syndrome and Obesity · doi:10.2147/dmso.s230061 · Cited by 54
“The maternal expression of KLF14 was associated with an increased risk of T2DM when carried on the maternal chromosome.(67)”
A Probabilistic Model to Predict Clinical Phenotypic Traits from Genome Sequencing
Chen, Y., Douville, C. B., Wang, C., Niknafs, N., Yeo, G. H. T., Guthrie, V. B., Carter, H. K., Stenson, P. D., Cooper, D. N., Li, B., et al. (2014) · PLoS Computational Biology · doi:10.1371/journal.pcbi.1003825 · Cited by 52
“While phasing is not currently considered in our models, knowledge of whether multiple variants are in the same haplotype or simply on the same chromosome could be informative with respect to their phenotypic impact [24–26].”
BackgroundSandovici, I., Hammerle, C. M., Ozanne, S. E., & Constância, M. (2013) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-013-1297-1 · Cited by 52
“The top-ranking association was for a CpG site located in the first intron of the FTO gene that showed a small (3.35”
InfluentialThe Genetics of Epigenetic Inheritance: Modes, Molecules, and Mechanisms
Schaefer, S., & Nadeau, J. H. (2015) · The Quarterly Review of Biology · doi:10.1086/683699 · Cited by 50
“For example, risk for breast cancer, basal cell carcinoma, and type 2 diabetes in humans depends in part on the parental origin of several single nucleotide polymorphisms (Kong et al. 2009).”
BackgroundThe Missing lnc(RNA) between the pancreatic β-cell and diabetes
Kameswaran, V., & Kaestner, K. H. (2014) · Frontiers in Genetics · doi:10.3389/fgene.2014.00200 · Cited by 54
Pidsley, R., Dempster, E. L., Troakes, C., Al‐Sarraj, S., & Mill, J. S. (2012) · Epigenetics · doi:10.4161/epi.7.2.18910 · Cited by 51
Searching for the human genetic factors standing in the way of universally effective vaccines
Mentzer, A. J., O’Connor, D., Pollard, A. J., & Hill, A. V. S. (2015) · Philosophical Transactions of the Royal Society B Biological Sciences · doi:10.1098/rstb.2014.0341 · Cited by 52
Common variants upstream of KDR encoding VEGFR2 and in TTC39B associate with endometriosis
Steinthorsdottir, V., Thorleifsson, G., Aradottir, K., Feenstra, B., Sigurdsson, A., Stefansdottir, L., Kristinsdottir, A. M., Zink, F., Halldorsson, G. H., Munk Nielsen, N., et al. (2016) · Nature Communications · doi:10.1038/ncomms12350 · Cited by 48
Self-citationLawson, H. A., Cady, J., Partridge, C., Wolf, J. B., Semenkovich, C. F., & Cheverud, J. M. (2011) · PLoS Genetics · doi:10.1371/journal.pgen.1002256 · Cited by 48
“Indeed a recent study identified parent-of-origin effects associated with T2D in the Icelandic genealogy database, finding the effects are different between males and females [61] and illustrating the complex connections among genomic sequence, genetic effects, environment, and disease risk.”
BackgroundZeng, Y., Amador, C., Xia, C., Marioni, R. E., Sproul, D., Walker, R. M., Morris, S. W., Bretherick, A. D., Canela‐Xandri, O., Boutin, T., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-09301-y · Cited by 46
Transcription Factor KLF14 and Metabolic Syndrome
Yang, Q., & Civelek, M. (2020) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2020.00091 · Cited by 49
“KLF14 is an imprinted gene and only the allele inherited from the mother is expressed (44); only the maternally inherited SNPs have significant associations with adipose tissue expression ofKLF14 (1).”
BackgroundComplete human recombination maps
Pálsson, G., Hardarson, M. T., Jónsson, H., Steinthórsdóttir, V., Stefánsson, Ó. A., Eggertsson, H. P., Gudjonsson, S. A., Olason, P. I., Gylfason, A., Másson, G., et al. (2025) · Nature · doi:10.1038/s41586-024-08450-5 · Cited by 46
Self-citation
Metadata
- 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
- Venue
- Nature
- Published
- 2009-12
- Volume
- 462
- Issue
- 7275
- Pages
- 868-874
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- 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
