genetic predisposition to disease


Summary: A latent susceptibility to disease at the genetic level, which may be activated under certain conditions.

Top Publications

  1. Levine D, Ek W, Zhang R, Liu X, Onstad L, Sather C, et al. A genome-wide association study identifies new susceptibility loci for esophageal adenocarcinoma and Barrett's esophagus. Nat Genet. 2013;45:1487-93 pubmed publisher
    ..We also refine a previously reported association with Barrett's esophagus near the putative tumor suppressor gene FOXF1 at 16q24 and extend our findings to now include esophageal adenocarcinoma. ..
  2. Wei Y, Xiong J, Zuo S, Chen F, Chen D, Wu T, et al. Association of polymorphisms on chromosome 9p21.3 region with increased susceptibility of abdominal aortic aneurysm in a Chinese Han population. J Vasc Surg. 2014;59:879-85 pubmed publisher
    ..The aim of this study was to evaluate the role of rs10757278 and rs1333049 in determining genetic susceptibility to AAA...
  3. Lacroux C, Perrin Chauvineau C, Corbière F, Aron N, Aguilar Calvo P, Torres J, et al. Genetic resistance to scrapie infection in experimentally challenged goats. J Virol. 2014;88:2406-13 pubmed publisher
    ..These results support the contention that the K222 goat prion protein variant provides a strong but not absolutely protective effect against classical scrapie. ..
  4. Rahman N. Realizing the promise of cancer predisposition genes. Nature. 2014;505:302-8 pubmed publisher
    ..However, there is also considerable potential for incorrect inferences and inappropriate clinical applications. Realizing the promise of cancer predisposition genes for science and medicine will thus require careful navigation. ..
  5. Fairfax B, Humburg P, Makino S, Naranbhai V, Wong D, Lau E, et al. Innate immune activity conditions the effect of regulatory variants upon monocyte gene expression. Science. 2014;343:1246949 pubmed publisher
    ..Thus, applying pathophysiologically relevant immune stimuli assists resolution of functional genetic variants. ..
  6. Robles Espinoza C, Harland M, Ramsay A, Aoude L, Quesada V, Ding Z, et al. POT1 loss-of-function variants predispose to familial melanoma. Nat Genet. 2014;46:478-481 pubmed publisher
    ..These findings suggest that POT1 variants predispose to melanoma formation via a direct effect on telomeres. ..
  7. Nurnberger J, Koller D, Jung J, Edenberg H, Foroud T, Guella I, et al. Identification of pathways for bipolar disorder: a meta-analysis. JAMA Psychiatry. 2014;71:657-64 pubmed publisher
    ..Genome-wide investigations provide systematic information regarding the neurobiology of psychiatric disorders...
  8. Mo J, Na K, Yu J, Chae S. Identification of the polymorphisms in IFITM1 gene and their association in a Korean population with ulcerative colitis. Immunol Lett. 2013;156:118-22 pubmed publisher
    ..002 and 0.042, respectively). These results suggest that the g.-1920G>A polymorphism in IFITM1 may be associated with susceptibility to UC. ..
  9. Maiga B, Dolo A, Touré O, Dara V, Tapily A, Campino S, et al. Human candidate polymorphisms in sympatric ethnic groups differing in malaria susceptibility in Mali. PLoS ONE. 2013;8:e75675 pubmed publisher
    ..Moreover, polymorphisms in FCER1A, RAD50, TNF, SLC22A4, and IL13 genes were correlated with antibody production (p-value<0.003). Further work is required to understand the mechanisms underpinning these genetic factors. ..

More Information


  1. Steinthorsdottir V, Thorleifsson G, Sulem P, Helgason H, Grarup N, Sigurdsson A, et al. Identification of low-frequency and rare sequence variants associated with elevated or reduced risk of type 2 diabetes. Nat Genet. 2014;46:294-8 pubmed publisher
    ..23, P = 3.9 × 10(-10) and OR = 1.47, P = 1.7 × 10(-5), respectively), and a rare (0.20%) frameshift variant in PDX1, encoding p.Gly218Alafs*12, associates with high risk of T2D (OR = 2.27, P = 7.3 × 10(-7)). ..
  2. MacArthur D, Manolio T, Dimmock D, Rehm H, Shendure J, Abecasis G, et al. Guidelines for investigating causality of sequence variants in human disease. Nature. 2014;508:469-76 pubmed publisher
    ..We propose guidelines for summarizing confidence in variant pathogenicity and highlight several areas that require further resource development. ..
  3. Raj T, Rothamel K, Mostafavi S, Ye C, Lee M, Replogle J, et al. Polarization of the effects of autoimmune and neurodegenerative risk alleles in leukocytes. Science. 2014;344:519-23 pubmed publisher
    ..This polarization implicates specific immune cell types in these diseases and points to the need to identify the cell-autonomous effects of disease susceptibility variants. ..
  4. Hazelett D, Rhie S, Gaddis M, Yan C, Lakeland D, Coetzee S, et al. Comprehensive functional annotation of 77 prostate cancer risk loci. PLoS Genet. 2014;10:e1004102 pubmed publisher
    ..Identification of such enhancer variants and their potential target genes represents a preliminary step in connecting risk to disease process...
  5. Orrú V, Steri M, Sole G, Sidore C, Virdis F, Dei M, et al. Genetic variants regulating immune cell levels in health and disease. Cell. 2013;155:242-56 pubmed publisher
    ..These results connect specific cellular phenotypes to specific genetic variants, helping to explicate their involvement in disease. ..
  6. Ghosh J, Pradhan S, Mittal B. Genome-wide-associated variants in migraine susceptibility: a replication study from North India. Headache. 2013;53:1583-94 pubmed publisher
    ..Furthermore, we checked the single nucleotide polymorphisms (SNPs) in strong linkage disequilibrium (LD) with the selected variants. We also undertook to predict the functional effect (in silico) of the variants...
  7. Qi Q, Chu A, Kang J, Huang J, Rose L, Jensen M, et al. Fried food consumption, genetic risk, and body mass index: gene-diet interaction analysis in three US cohort studies. BMJ. 2014;348:g1610 pubmed publisher
    ..To examine the interactions between genetic predisposition and consumption of fried food in relation to body mass index (BMI) and obesity...
  8. Ma L, Chung W. The genetic basis of pulmonary arterial hypertension. Hum Genet. 2014;133:471-9 pubmed publisher
    ..Clinical genetic testing is available for PAH and should be considered in families to allow for more definitive risk stratification and allow for reproductive planning. ..
  9. Noth I, Zhang Y, Ma S, Flores C, Barber M, Huang Y, et al. Genetic variants associated with idiopathic pulmonary fibrosis susceptibility and mortality: a genome-wide association study. Lancet Respir Med. 2013;1:309-317 pubmed publisher
    ..Our aim was to identify additional common variants associated with susceptibility and ultimately mortality in IPF...
  10. Finch A, Lubinski J, Møller P, Singer C, Karlan B, Senter L, et al. Impact of oophorectomy on cancer incidence and mortality in women with a BRCA1 or BRCA2 mutation. J Clin Oncol. 2014;32:1547-53 pubmed publisher
  11. Speedy H, Di Bernardo M, Sava G, Dyer M, Holroyd A, Wang Y, et al. A genome-wide association study identifies multiple susceptibility loci for chronic lymphocytic leukemia. Nat Genet. 2014;46:56-60 pubmed publisher
    ..33 (TERT, rs10069690, P = 1.12 × 10(-10)) and 8q22.3 (rs2511714, P = 2.90 × 10(-9)). These findings provide further insights into the genetic and biological basis of inherited genetic susceptibility to CLL. ..
  12. Liu C, Mou S, Cai Y. FTO gene variant and risk of overweight and obesity among children and adolescents: a systematic review and meta-analysis. PLoS ONE. 2013;8:e82133 pubmed publisher
    ..However, the results have been inconsistent. In this study, we performed a meta-analysis to clarify the association of FTO gene polymorphisms with overweight/obesity risk among children and adolescents...
  13. Zhang S, Xiao J, Ren Q, Han X, Tang Y, Yang W, et al. Replication of association study between type 2 diabetes mellitus and IGF2BP2 in Han Chinese population. Chin Med J (Engl). 2013;126:4013-8 pubmed
    ..It is necessary to systematically evaluate the contribution of common variants in IGF2BP2 to T2DM in Chinese Han population...
  14. Qiu R, Zhang H, Zhao H, Li J, Guo C, Gong Y, et al. Genetic variants on 17q21 are associated with ankylosing spondylitis susceptibility and severity in a Chinese Han population. Scand J Rheumatol. 2013;42:469-72 pubmed publisher
    ..The aim of this study was to test whether orosomucoid like 3 (ORMDL3) and 17q21 variants are associated with susceptibility to ankylosing spondylitis (AS) in a Chinese population...
  15. Wu Y, Fu H, Zhang H, Huang H, Chen M, Zhang L, et al. Cyclin D1 (CCND1) G870A polymorphisms and cervical cancer susceptibility: a meta-analysis based on ten case-control studies. Tumour Biol. 2014;35:6913-8 pubmed publisher
    ..In summary, the present meta-analysis provides evidence that genotypes for the cyclin D1 (CCND1) G870A polymorphism may be not associated with genetic susceptibility of cervical cancer...
  16. Antoniou A, Casadei S, Heikkinen T, Barrowdale D, Pylkäs K, Roberts J, et al. Breast-cancer risk in families with mutations in PALB2. N Engl J Med. 2014;371:497-506 pubmed publisher
    ..Germline loss-of-function mutations in PALB2 are known to confer a predisposition to breast cancer. However, the lifetime risk of breast cancer that is conferred by such mutations remains unknown...
  17. Beaudoin M, Goyette P, Boucher G, Lo K, Rivas M, Stevens C, et al. Deep resequencing of GWAS loci identifies rare variants in CARD9, IL23R and RNF186 that are associated with ulcerative colitis. PLoS Genet. 2013;9:e1003723 pubmed publisher
    ..Rather, these are expected to help focus functional studies of the corresponding disease loci...
  18. Couch F, Nathanson K, Offit K. Two decades after BRCA: setting paradigms in personalized cancer care and prevention. Science. 2014;343:1466-70 pubmed publisher
  19. Shi J, Yang X, Ballew B, Rotunno M, Calista D, Fargnoli M, et al. Rare missense variants in POT1 predispose to familial cutaneous malignant melanoma. Nat Genet. 2014;46:482-6 pubmed publisher
    ..We also identified two rare recurrent POT1 variants in US and French familial melanoma cases. Our findings suggest that POT1 is a major susceptibility gene for familial melanoma in several populations. ..
  20. Blair D, Lyttle C, Mortensen J, Bearden C, Jensen A, Khiabanian H, et al. A nondegenerate code of deleterious variants in Mendelian loci contributes to complex disease risk. Cell. 2013;155:70-80 pubmed publisher
    ..Overall, this study illustrates a complementary approach for mapping complex disease loci and provides unique predictions concerning the etiologies of specific diseases. ..
  21. Paul D, Soranzo N, Beck S. Functional interpretation of non-coding sequence variation: concepts and challenges. Bioessays. 2014;36:191-9 pubmed publisher
    ..There is a pressing need to translate genetic signals into biological mechanisms, leading to prognostic, diagnostic and therapeutic advances. ..
  22. Beecham A, Patsopoulos N, Xifara D, Davis M, Kemppinen A, Cotsapas C, et al. Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis. Nat Genet. 2013;45:1353-60 pubmed publisher
    ..This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals...
  23. Speakman J. Functional analysis of seven genes linked to body mass index and adiposity by genome-wide association studies: a review. Hum Hered. 2013;75:57-79 pubmed publisher
    ..These functions may contribute to their effects on the obese phenotype...
  24. Vasquez J, Fardo D, Estus S. ABCA7 expression is associated with Alzheimer's disease polymorphism and disease status. Neurosci Lett. 2013;556:58-62 pubmed publisher
    ..We interpret our findings as suggesting a model wherein increased ABCA7 expression reduces AD risk and that the increased ABCA7 observed in AD reflects an inadequate compensatory change. ..
  25. Willer C, Schmidt E, Sengupta S, Peloso G, Gustafsson S, Kanoni S, et al. Discovery and refinement of loci associated with lipid levels. Nat Genet. 2013;45:1274-1283 pubmed publisher
    ..Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research...
  26. Zuk O, Schaffner S, Samocha K, Do R, Hechter E, Kathiresan S, et al. Searching for missing heritability: designing rare variant association studies. Proc Natl Acad Sci U S A. 2014;111:E455-64 pubmed publisher
    ..In particular, a well-powered RVAS should involve discovery sets with at least 25,000 cases, together with a substantial replication set. ..
  27. Xiong X, Cho M, Cai X, Cheng J, Jing X, Cen J, et al. A common variant in pre-miR-146 is associated with coronary artery disease risk and its mature miRNA expression. Mutat Res. 2014;761:15-20 pubmed publisher
    ..Our data provide the first evidence that the miR-146a rs2910164 polymorphism is associated with increased risk of CAD in Chinese Han population, which may be through influencing the expression levels of the miRNA. ..
  28. Flannick J, Beer N, Bick A, Agarwala V, Molnes J, Gupta N, et al. Assessing the phenotypic effects in the general population of rare variants in genes for a dominant Mendelian form of diabetes. Nat Genet. 2013;45:1380-5 pubmed publisher
    ..Accurate estimates of variant effect sizes from population-based sequencing are needed to avoid falsely predicting a substantial fraction of individuals as being at risk for MODY or other Mendelian diseases...
  29. Gylfe A, Katainen R, Kondelin J, Tanskanen T, Cajuso T, Hänninen U, et al. Eleven candidate susceptibility genes for common familial colorectal cancer. PLoS Genet. 2013;9:e1003876 pubmed publisher
    ..Additional genetic validation in other populations is required to provide firm evidence for causality, as well as to characterize the natural history of the respective phenotypes...
  30. Trynka G, Raychaudhuri S. Using chromatin marks to interpret and localize genetic associations to complex human traits and diseases. Curr Opin Genet Dev. 2013;23:635-41 pubmed publisher
    ..We discuss the efforts to integrate common trait-associated variants with genomic annotations. Finally, we highlight some caveats of these approaches and outline future directions for improvement. ..
  31. Winsvold B, Bettella F, Witoelar A, Anttila V, Gormley P, Kurth T, et al. Shared genetic risk between migraine and coronary artery disease: A genome-wide analysis of common variants. PLoS ONE. 2017;12:e0185663 pubmed publisher
    ..Understanding the biological mechanisms underpinning this shared risk is likely to improve our understanding of both disorders...
  32. Mandelker D, Zhang L, Kemel Y, Stadler Z, Joseph V, Zehir A, et al. Mutation Detection in Patients With Advanced Cancer by Universal Sequencing of Cancer-Related Genes in Tumor and Normal DNA vs Guideline-Based Germline Testing. JAMA. 2017;318:825-835 pubmed publisher
    ..Guidelines for cancer genetic testing based on family history may miss clinically actionable genetic changes with established implications for cancer screening or prevention...
  33. Matsubara D, Soda M, Yoshimoto T, Amano Y, Sakuma Y, Yamato A, et al. Inactivating mutations and hypermethylation of the NKX2-1/TTF-1 gene in non-terminal respiratory unit-type lung adenocarcinomas. Cancer Sci. 2017;108:1888-1896 pubmed publisher
    ..The genetic or epigenetic inactivation of NKX2-1/TTF-1 may play an essential role in the development and aberrant differentiation of non-TRU-type lung adenocarcinomas. ..
  34. Hu R, Zhong P, Xiong L, Duan L. Long Noncoding RNA Cancer Susceptibility Candidate 8 Suppresses the Proliferation of Bladder Cancer Cells via Regulating Glycolysis. DNA Cell Biol. 2017;36:767-774 pubmed publisher
    ..Collectively, our findings uncovered the pivotal role of CASC8 in bladder tumorigenesis and suggested that CASC8 may function as a candidate biomarker for the diagnosis of bladder cancer. ..
  35. Pérez Rubio G, López Flores L, Ramirez Venegas A, Noé Díaz V, García Gómez L, Ambrocio Ortiz E, et al. Genetic polymorphisms in CYP2A6 are associated with a risk of cigarette smoking and predispose to smoking at younger ages. Gene. 2017;628:205-210 pubmed publisher
    ..The present study shows that in Mexican mestizos, the analyzed SNPs confer greater risk in terms of consumption and age of onset. ..
  36. Dos Santos I, Genre J, Marques D, da Silva A, Dos Santos J, de Araújo J, et al. A new panel of SNPs to assess thyroid carcinoma risk: a pilot study in a Brazilian admixture population. BMC Med Genet. 2017;18:140 pubmed publisher
    ..However, complementary studies including a control group with samples obtained from healthy subjects in Rio Grande do Norte state, should be conducted to confirm these results. ..
  37. Tschope C, Muller I, Xia Y, Savvatis K, Pappritz K, Pinkert S, et al. NOD2 (Nucleotide-Binding Oligomerization Domain 2) Is a Major Pathogenic Mediator of Coxsackievirus B3-Induced Myocarditis. Circ Heart Fail. 2017;10: pubmed publisher
    ..NOD2 is an important mediator in the viral uptake and inflammatory response during the pathogenesis of CVB3 myocarditis. ..
  38. Grampp S, Schmid V, Salama R, Lauer V, Kranz F, Platt J, et al. Multiple renal cancer susceptibility polymorphisms modulate the HIF pathway. PLoS Genet. 2017;13:e1006872 pubmed publisher
    ..The alignment of multiple sites in the HIF cis-acting apparatus with RCC-susceptibility polymorphisms strongly supports a causal model in which minor variation in this pathway exerts significant effects on RCC development. ..
  39. Roy A, Ramalinga M, Kim O, Chijioke J, Lynch S, Byers S, et al. Multiple roles of RARRES1 in prostate cancer: Autophagy induction and angiogenesis inhibition. PLoS ONE. 2017;12:e0180344 pubmed publisher
    ..Future studies will help determine the in vivo mechanisms by which RARRES1 may serve as a target for therapeutic intervention both in cancer and in angiogenesis-related disorders. ..
  40. Lehman A, Thouta S, Mancini G, Naidu S, van Slegtenhorst M, McWalter K, et al. Loss-of-Function and Gain-of-Function Mutations in KCNQ5 Cause Intellectual Disability or Epileptic Encephalopathy. Am J Hum Genet. 2017;101:65-74 pubmed publisher
    ..Specifically, both loss-of-function and gain-of-function KCNQ5 mutations, associated with increased excitability and decreased repolarization reserve, lead to pathophysiology. ..
  41. Sakowicz A, Pietrucha T, Rybak Krzyszkowska M, Huras H, Gach A, Sakowicz B, et al. Double hit of NEMO gene in preeclampsia. PLoS ONE. 2017;12:e0180065 pubmed publisher
    ..Our observations may offer a new insight into the genetic etiology and pathogenesis of preeclampsia...
  42. Lu Q, Zhang J, Zhao N, Wang H, Tong Q, Wang S. Association of IL-6 Gene (-174 and -572 G/C) Polymorphisms with Proliferative Diabetic Retinopathy of Type 2 Diabetes in a Chinese Population. Ophthalmic Res. 2017;58:162-167 pubmed publisher
    ..IL-6 genotypes of rs1800795 GC and rs1800796 GG might point to a relatively high risk for T2D patients suffering from PDR in a Chinese population and they were associated with elevation of IL-6 expression in both mRNA and protein. ..
  43. Gu F, Zhang H, Hyland P, Berndt S, Gapstur S, Wheeler W, et al. Inherited variation in circadian rhythm genes and risks of prostate cancer and three other cancer sites in combined cancer consortia. Int J Cancer. 2017;141:1794-1802 pubmed publisher
    ..These findings support a potential role for circadian rhythm and melatonin pathways in prostate carcinogenesis. Further functional studies are needed to better understand the underlying biologic mechanisms. ..
  44. Muñoz I, Morel B, Medina Carmona E, Pey A. A mechanism for cancer-associated inactivation of NQO1 due to P187S and its reactivation by the consensus mutation H80R. FEBS Lett. 2017;591:2826-2835 pubmed publisher
    ..Our analyses illustrate how single amino acid changes can profoundly affect structural and mechanistic features of protein functional traits, with implications for our understanding of protein evolution and human disease. ..
  45. Polak P, Kim J, Braunstein L, Karlic R, Haradhavala N, Tiao G, et al. A mutational signature reveals alterations underlying deficient homologous recombination repair in breast cancer. Nat Genet. 2017;49:1476-1486 pubmed publisher
  46. Kuo D, Sokol J, Minogue P, Berthoud V, Slavotinek A, Beyer E, et al. Characterization of a variant of gap junction protein ?8 identified in a family with hereditary cataract. PLoS ONE. 2017;12:e0183438 pubmed publisher
    ..Our study demonstrates that the mutant protein localized to the plasma membrane and formed functional intercellular channels. These data suggest that GJA8 c.658A>G is most likely a benign rare variant. ..
  47. Nebot Bral L, Brandao D, Verlingue L, Rouleau E, Caron O, Despras E, et al. Hypermutated tumours in the era of immunotherapy: The paradigm of personalised medicine. Eur J Cancer. 2017;84:290-303 pubmed publisher
    ..This breakthrough represents a turning point in the management of these hypermutated tumours and paves the way for broader strategies in immunoprecision medicine. ..
  48. Zeng C, Fang C, Weng H, Xu X, Wu T, Li W. B-cell lymphocyte kinase polymorphisms rs13277113, rs2736340, and rs4840568 and risk of autoimmune diseases: A meta-analysis. Medicine (Baltimore). 2017;96:e7855 pubmed publisher
    ..Hence, it is meaningful to conduct a comprehensive analysis...
  49. Nishimura R, Seggewiss H, Schaff H. Hypertrophic Obstructive Cardiomyopathy: Surgical Myectomy and Septal Ablation. Circ Res. 2017;121:771-783 pubmed publisher
    ..The final decision as to which approach should be selected in any given patient is dependent up patient preference and the availability and experience of the operator and institution at which the patient is being treated. ..
  50. Sobalska Kwapis M, Suchanecka A, Słomka M, Siewierska Górska A, Kepka E, Strapagiel D. Genetic association of FTO/IRX region with obesity and overweight in the Polish population. PLoS ONE. 2017;12:e0180295 pubmed publisher
    ..Our study demonstrated how tested SNPs make differential contributions to obesity and overweight risk. We revealed sex dependent differences in the distribution of tested loci which are associated with BMI in the population of Poles. ..
  51. Khella M, Hamdy N, Amin A, El Mesallamy H. The (FTO) gene polymorphism is associated with metabolic syndrome risk in Egyptian females: a case- control study. BMC Med Genet. 2017;18:101 pubmed publisher
    ..The association of this genetic polymorphism with ALT levels needs to be studied in other populations with larger sample size. ..
  52. de Castro Catala M, Mora Solano A, Kwapil T, Cristóbal Narváez P, Sheinbaum T, Racioppi A, et al. The genome-wide associated candidate gene ZNF804A and psychosis-proneness: Evidence of sex-modulated association. PLoS ONE. 2017;12:e0185072 pubmed publisher
    ..The findings of the present study support the inclusion of ZNF804 variability in studies of the vulnerability for the development of psychopathology in non-clinical samples and consideration of sex as a moderator of this association. ..
  53. Stiburkova B, Pavelcova K, Zavada J, Petru L, Šimek P, Cepek P, et al. Functional non-synonymous variants of ABCG2 and gout risk. Rheumatology (Oxford). 2017;56:1982-1992 pubmed publisher
    ..Non-synonymous allelic variants of ABCG2 had a significant effect on earlier onset of gout and the presence of a familial gout history. ABCG2 should thus be considered a common and significant risk factor for gout. ..