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Excess maternal tra...
Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes
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- Prasad, Rashmi B. (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Lessmark, Anna (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Almgren, Peter (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Kovacs, Györgyi (författare)
- Heart Center Foundation
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- Hansson, Ola (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Oskolkov, Nikolay (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Vitai, Marta (författare)
- Heart Center Foundation
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- Ladenvall, Claes (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Kovacs, Peter (författare)
- Leipzig University
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- Fadista, Joao (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Lachmann, Michael (författare)
- Santa Fe Institute
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- Zhou, Yuedan (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Sonestedt, Emily (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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- Poon, Wenny (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Wollheim, Claes B. (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Skåne University Hospital
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- Orho-Melander, Marju (författare)
- Lund University,Lunds universitet,Diabetes - kardiovaskulär sjukdom,Forskargrupper vid Lunds universitet,Diabetes - Cardiovascular Disease,Lund University Research Groups,Skåne University Hospital
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- Stumvoll, Michael (författare)
- Leipzig University
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- Tuomi, Tiinamaija (författare)
- Folkhälsan Research Center,Helsinki University Central Hospital
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- Pääbo, Svante (författare)
- Max Planck Institute for Evolutionary Anthropology
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- Koranyi, Laszlo (författare)
- Heart Center Foundation
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- Groop, Leif (författare)
- Lund University,Lunds universitet,Translationell Muskel Forskning,Forskargrupper vid Lunds universitet,Translational Muscle Research,Lund University Research Groups,Institute for Molecular Medicine Finland (FIMM)
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(creator_code:org_t)
- 2016-05-07
- 2016
- Engelska 12 s.
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Ingår i: Diabetologia. - : Springer Science and Business Media LLC. - 0012-186X .- 1432-0428. ; 59:8, s. 1702-1713
- Relaterad länk:
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http://dx.doi.org/10...
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https://link.springe...
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https://lup.lub.lu.s...
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https://doi.org/10.1...
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Abstract
Ämnesord
Stäng
- Aims/hypothesis: Genome-wide association studies (GWAS) have identified more than 65 genetic loci associated with risk of type 2 diabetes. However, the contribution of distorted parental transmission of alleles to risk of type 2 diabetes has been mostly unexplored. Our goal was therefore to search for parent-of-origin effects (POE) among type 2 diabetes loci in families. Methods: Families from the Botnia study (n = 4,211, 1,083 families) were genotyped for 72 single-nucleotide polymorphisms (SNPs) associated with type 2 diabetes and assessed for POE on type 2 diabetes. The family-based Hungarian Transdanubian Biobank (HTB) (n = 1,463, >135 families) was used to replicate SNPs showing POE. Association of type 2 diabetes loci within families was also tested. Results: Three loci showed nominal POE, including the previously reported variants in KCNQ1, for type 2 diabetes in families from Botnia (rs2237895: pPOE = 0.037), which can be considered positive controls. The strongest POE was seen for rs7578597 SNP in the THADA gene, showing excess transmission of the maternal risk allele T to diabetic offspring (Botnia: pPOE = 0.01; HTB pPOE = 0.045). These data are consistent with previous evidence of allelic imbalance for expression in islets, suggesting that the THADA gene can be imprinted in a POE-specific fashion. Five CpG sites, including those flanking rs7578597, showed differential methylation between diabetic and non-diabetic donor islets. Conclusions/interpretation: Taken together, the data emphasise the need for genetic studies to consider from which parent an offspring has inherited a susceptibility allele.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Medicinsk genetik (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Medical Genetics (hsv//eng)
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Endokrinologi och diabetes (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Endocrinology and Diabetes (hsv//eng)
Nyckelord
- Families
- Genetic association studies
- KCNQ1
- Maternal effects
- Methylation
- Parent-of-origin
- Parental transmission
- THADA
- Type 2 diabetes
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- art (ämneskategori)
- ref (ämneskategori)
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Till lärosätets databas
- Av författaren/redakt...
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Prasad, Rashmi B ...
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Lessmark, Anna
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Almgren, Peter
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Kovacs, Györgyi
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Hansson, Ola
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Oskolkov, Nikola ...
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visa fler...
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Vitai, Marta
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Ladenvall, Claes
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Kovacs, Peter
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Fadista, Joao
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Lachmann, Michae ...
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Zhou, Yuedan
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Sonestedt, Emily
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Poon, Wenny
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Wollheim, Claes ...
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Orho-Melander, M ...
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Stumvoll, Michae ...
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Tuomi, Tiinamaij ...
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Pääbo, Svante
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Koranyi, Laszlo
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Groop, Leif
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Diabetologia
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