The genetic architecture of type 2 diabetes
The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, t...
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| Format: | Article |
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Nature Publishing Group
2018
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| Online Access: | http://hdl.handle.net/1721.1/116695 https://orcid.org/0000-0002-7250-4107 |
| _version_ | 1826214623082184704 |
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| author | Altshuler, David |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Altshuler, David |
| author_sort | Altshuler, David |
| collection | MIT |
| description | The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes. |
| first_indexed | 2024-09-23T16:08:46Z |
| format | Article |
| id | mit-1721.1/116695 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T16:08:46Z |
| publishDate | 2018 |
| publisher | Nature Publishing Group |
| record_format | dspace |
| spelling | mit-1721.1/1166952022-10-02T06:39:11Z The genetic architecture of type 2 diabetes Altshuler, David Massachusetts Institute of Technology. Department of Biology Altshuler, David M The genetic architecture of common traits, including the number, frequency, and effect sizes of inherited variants that contribute to individual risk, has been long debated. Genome-wide association studies have identified scores of common variants associated with type 2 diabetes, but in aggregate, these explain only a fraction of the heritability of this disease. Here, to test the hypothesis that lower-frequency variants explain much of the remainder, the GoT2D and T2D-GENES consortia performed whole-genome sequencing in 2,657 European individuals with and without diabetes, and exome sequencing in 12,940 individuals from five ancestry groups. To increase statistical power, we expanded the sample size via genotyping and imputation in a further 111,548 subjects. Variants associated with type 2 diabetes after sequencing were overwhelmingly common and most fell within regions previously identified by genome-wide association studies. Comprehensive enumeration of sequence variation is necessary to identify functional alleles that provide important clues to disease pathophysiology, but large-scale sequencing does not support the idea that lower-frequency variants have a major role in predisposition to type 2 diabetes. 2018-06-29T15:07:01Z 2018-06-29T15:07:01Z 2016-08 2018-06-28T14:45:44Z Article http://purl.org/eprint/type/JournalArticle 0028-0836 1476-4687 http://hdl.handle.net/1721.1/116695 Fuchsberger, Christian et al. “The Genetic Architecture of Type 2 Diabetes.” Nature 536, 7614 (July 2016): 41–47 © 2016 Macmillan Publishers Limited, part of Springer Nature https://orcid.org/0000-0002-7250-4107 http://dx.doi.org/10.1038/NATURE18642 Nature Creative Commons Attribution-Noncommercial-Share Alike http://creativecommons.org/licenses/by-nc-sa/4.0/ application/pdf Nature Publishing Group PMC |
| spellingShingle | Altshuler, David The genetic architecture of type 2 diabetes |
| title | The genetic architecture of type 2 diabetes |
| title_full | The genetic architecture of type 2 diabetes |
| title_fullStr | The genetic architecture of type 2 diabetes |
| title_full_unstemmed | The genetic architecture of type 2 diabetes |
| title_short | The genetic architecture of type 2 diabetes |
| title_sort | genetic architecture of type 2 diabetes |
| url | http://hdl.handle.net/1721.1/116695 https://orcid.org/0000-0002-7250-4107 |
| work_keys_str_mv | AT altshulerdavid thegeneticarchitectureoftype2diabetes AT altshulerdavid geneticarchitectureoftype2diabetes |