You are here

Nat Biotechnol DOI:10.1038/nbt.2422

Interpreting noncoding genetic variation in complex traits and human disease.

Publication TypeJournal Article
Year of Publication2012
AuthorsWard, LD, Kellis, M
JournalNat Biotechnol
Date Published2012 Nov
KeywordsAnimals, Chromosome Mapping, Genetic Predisposition to Disease, Genetic Testing, Genetic Variation, Humans, Quantitative Trait Loci, RNA, Untranslated, Sequence Analysis, DNA

Association studies provide genome-wide information about the genetic basis of complex disease, but medical research has focused primarily on protein-coding variants, owing to the difficulty of interpreting noncoding mutations. This picture has changed with advances in the systematic annotation of functional noncoding elements. Evolutionary conservation, functional genomics, chromatin state, sequence motifs and molecular quantitative trait loci all provide complementary information about the function of noncoding sequences. These functional maps can help with prioritizing variants on risk haplotypes, filtering mutations encountered in the clinic and performing systems-level analyses to reveal processes underlying disease associations. Advances in predictive modeling can enable data-set integration to reveal pathways shared across loci and alleles, and richer regulatory models can guide the search for epistatic interactions. Lastly, new massively parallel reporter experiments can systematically validate regulatory predictions. Ultimately, advances in regulatory and systems genomics can help unleash the value of whole-genome sequencing for personalized genomic risk assessment, diagnosis and treatment.


Alternate JournalNat. Biotechnol.
PubMed ID23138309
PubMed Central IDPMC3703467
Grant ListR01 HG004037 / HG / NHGRI NIH HHS / United States
RC1 HG005334 / HG / NHGRI NIH HHS / United States
R01HG004037 / HG / NHGRI NIH HHS / United States
RC1HG005334 / HG / NHGRI NIH HHS / United States