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Comprehensive assoc...
Comprehensive association testing of common mitochondrial DNA variation in metabolic disease
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Saxena, R (author)
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de Bakker, PIW (author)
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Singer, K (author)
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Mootha, V (author)
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Burtt, N (author)
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Hirschhorn, JN (author)
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Gaudet, D (author)
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Isomaa, B (author)
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Daly, MJ (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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Ardlie, KG (author)
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Altshuler, D (author)
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(creator_code:org_t)
- 2006
- 2006
- English.
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In: American Journal of Human Genetics. - 0002-9297. ; 79:1, s. 54-61
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Abstract
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- Many lines of evidence implicate mitochondria in phenotypic variation: ( a) rare mutations in mitochondrial proteins cause metabolic, neurological, and muscular disorders; ( b) alterations in oxidative phosphorylation are characteristic of type 2 diabetes, Parkinson disease, Huntington disease, and other diseases; and ( c) common missense variants in the mitochondrial genome ( mtDNA) have been implicated as having been subject to natural selection for adaptation to cold climates and contributing to "energy deficiency" diseases today. To test the hypothesis that common mtDNA variation influences human physiology and disease, we identified all 144 variants with frequency > 1% in Europeans from > 900 publicly available European mtDNA sequences and selected 64 tagging single-nucleotide polymorphisms that efficiently capture all common variation ( except the hypervariable D-loop). Next, we evaluated the complete set of common mtDNA variants for association with type 2 diabetes in a sample of 3,304 diabetics and 3,304 matched nondiabetic individuals. Association of mtDNA variants with other metabolic traits ( body mass index, measures of insulin secretion and action, blood pressure, and cholesterol) was also tested in subsets of this sample. We did not find a significant association of common mtDNA variants with these metabolic phenotypes. Moreover, we failed to identify any physiological effect of alleles that were previously proposed to have been adaptive for energy metabolism in human evolution. More generally, this comprehensive association-testing framework can readily be applied to other diseases for which mitochondrial dysfunction has been implicated.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
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- art (subject category)
- ref (subject category)
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- By the author/editor
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Saxena, R
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de Bakker, PIW
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Singer, K
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Mootha, V
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Burtt, N
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Hirschhorn, JN
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show more...
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Gaudet, D
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Isomaa, B
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Daly, MJ
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Groop, Leif
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Ardlie, KG
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Altshuler, D
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show less...
- 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