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  • Han, Buhm (author)

A method to decipher pleiotropy by detecting underlying heterogeneity driven by hidden subgroups applied to autoimmune and neuropsychiatric diseases

  • Article/chapterEnglish2016

Publisher, publication year, extent ...

  • 2016-05-16
  • Springer Science and Business Media LLC,2016
  • printrdacarrier

Numbers

  • LIBRIS-ID:oai:DiVA.org:umu-124226
  • https://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-124226URI
  • https://doi.org/10.1038/ng.3572DOI
  • http://kipublications.ki.se/Default.aspx?queryparsed=id:133834123URI

Supplementary language notes

  • Language:English
  • Summary in:English

Part of subdatabase

Classification

  • Subject category:ref swepub-contenttype
  • Subject category:art swepub-publicationtype

Notes

  • There is growing evidence of shared risk alleles for complex traits (pleiotropy), including autoimmune and neuropsychiatric diseases. This might be due to sharing among all individuals (whole-group pleiotropy) or a subset of individuals in a genetically heterogeneous cohort (subgroup heterogeneity). Here we describe the use of a well-powered statistic, BUHMBOX, to distinguish between those two situations using genotype data. We observed a shared genetic basis for 11 autoimmune diseases and type 1 diabetes (T1D; P < 1 x 10(-4)) and for 11 autoimmune diseases and rheumatoid arthritis (RA; P < 1 x 10(-3)). This sharing was not explained by subgroup heterogeneity (corrected P-BUHMBOX > 0.2; 6,670 T1D cases and 7,279 RA cases). Genetic sharing between seronegative and seropostive RA (P < 1 x 10(-9)) had significant evidence of subgroup heterogeneity, suggesting a subgroup of seropositive-like cases within seronegative cases (P-BUHMBOX = 0.008; 2,406 seronegative RA cases). We also observed a shared genetic basis for major depressive disorder (MDD) and schizophrenia (P < 1 x 10(-4)) that was not explained by subgroup heterogeneity (P-BUHMBOX = 0.28; 9,238 MDD cases).

Subject headings and genre

Added entries (persons, corporate bodies, meetings, titles ...)

  • Pouget, Jennie G. (author)
  • Slowikowski, Kamil (author)
  • Stahl, Eli (author)
  • Lee, Cue Hyunkyu (author)
  • Diogo, Dorothee (author)
  • Hu, Xinli (author)
  • Park, Yu Rang (author)
  • Kim, Eunji (author)
  • Gregersen, Peter K. (author)
  • Dahlqvist, Solbritt RantapääUmeå universitet,Reumatologi(Swepub:umu)sora0001 (author)
  • Worthington, Jane (author)
  • Martin, Javier (author)
  • Eyre, Steve (author)
  • Klareskog, LarsKarolinska Institutet (author)
  • Huizinga, Tom (author)
  • Chen, Wei-Min (author)
  • Onengut-Gumuscu, Suna (author)
  • Rich, Stephen S. (author)
  • Wray, Naomi R. (author)
  • Raychaudhuri, Soumya (author)
  • Umeå universitetReumatologi (creator_code:org_t)

Related titles

  • In:Nature Genetics: Springer Science and Business Media LLC48:7, s. 803-+1061-40361546-1718

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