The reference human genome demonstrates high risk of type 1 diabetes and other disorders

Rong Chen, Atul J. Butte

Research output: Chapter in Book/Report/Conference proceedingConference contributionpeer-review

16 Scopus citations

Abstract

Personal genome resequencing has provided promising lead to personalized medicine. However, due to the limited samples and the lack of case/control design, current interpretation of personal genome sequences has been mainly focused on the identification and functional annotation of the DNA variants that are different from the reference genome. The reference genome was deduced from a collection of DNAs from anonymous individuals, some of whom might be carriers of disease risk alleles. We queried the reference genome against a large high-quality disease-SNP association database and found 3,556 disease-susceptible variants, including 15 rare variants. We assessed the likelihood ratio for risk for the reference genome on 104 diseases and found high risk for type 1 diabetes (T1D) and hypertension. We further demonstrated that the risk of T1D was significantly higher in the reference genome than those in a healthy patient with a whole human genome sequence. We found that the high T1D risk was mainly driven by a R260W mutation in PTPN22 in the reference genome. Therefore, we recommend that the disease-susceptible variants in the reference genome should be taken into consideration and future genome sequences should be interpreted with curated and predicted disease-susceptible loci to assess personal disease risk.

Original languageEnglish
Title of host publicationPacific Symposium on Biocomputing 2011, PSB 2011
Pages231-242
Number of pages12
StatePublished - 2011
Externally publishedYes
Event16th Pacific Symposium on Biocomputing, PSB 2011 - Kohala Coast, HI, United States
Duration: 3 Jan 20117 Jan 2011

Publication series

NamePacific Symposium on Biocomputing 2011, PSB 2011

Conference

Conference16th Pacific Symposium on Biocomputing, PSB 2011
Country/TerritoryUnited States
CityKohala Coast, HI
Period3/01/117/01/11

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