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A Novel Test for Re...
A Novel Test for Recessive Contributions to Complex Diseases Implicates Bardet-Biedl Syndrome Gene BBS10 in Idiopathic Type 2 Diabetes and Obesity
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Lim, Elaine T. (author)
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Liu, Yangfan P. (author)
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Chan, Yingleong (author)
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- Tuomi, Tiinamaija (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Karajamaki, AnnMari (author)
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Madsen, Erik (author)
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Altshuler, David M. (author)
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Raychaudhuri, Soumya (author)
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- Groop, Leif (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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Fannick, Jason (author)
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Hirschhorn, Joel N. (author)
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Katsanis, Nicholas (author)
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- Daly, Mark (author)
- Lund University,Lunds universitet,Genomik, diabetes och endokrinologi,Forskargrupper vid Lunds universitet,Genomics, Diabetes and Endocrinology,Lund University Research Groups
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(creator_code:org_t)
- Elsevier BV, 2014
- 2014
- English.
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In: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297. ; 95:5, s. 509-520
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http://www.ncbi.nlm....
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http://dx.doi.org/10...
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Abstract
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- Rare-variant association studies in common, complex diseases are customarily conducted under an additive risk model in both single-variant and burden testing. Here, we describe a method to improve detection of rare recessive variants in complex diseases termed RAFT (recessive-allele-frequency-based test). We found that RAFT outperforms existing approaches when the variant influences disease risk in a recessive manner on simulated data. We then applied our method to 1,791 Finnish individuals with type 2 diabetes (T2D) and 2,657 matched control subjects. In BBS10, we discovered a rare variant (c.1189A>G [p.Ile397Val]; rs202042386) that confers risk of T2D in a recessive state (p = 1.38 x 10(-6)) and would be missed by conventional methods. Testing of this variant in an established in vivo zebrafish model confirmed the variant to be pathogenic. Taken together, these data suggest that RAFT can effectively reveal rare recessive contributions to complex diseases overlooked by conventional association tests.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
Publication and Content Type
- art (subject category)
- ref (subject category)
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- By the author/editor
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Lim, Elaine T.
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Liu, Yangfan P.
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Chan, Yingleong
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Tuomi, Tiinamaij ...
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Karajamaki, AnnM ...
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Madsen, Erik
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show more...
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Altshuler, David ...
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Raychaudhuri, So ...
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Groop, Leif
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Fannick, Jason
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Hirschhorn, Joel ...
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Katsanis, Nichol ...
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Daly, Mark
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Medical Genetics
- Articles in the publication
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American Journal ...
- By the university
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Lund University