Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes

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Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes. / Prasad, Rashmi B.; Lessmark, Anna; Almgren, Peter; Kovacs, Györgyi; Hansson, Ola; Oskolkov, Nikolay; Vitai, Marta; Ladenvall, Claes; Kovacs, Peter; Fadista, Joao; Lachmann, Michael; Zhou, Yuedan; Sonestedt, Emily; Poon, Wenny; Wollheim, Claes B.; Orho-Melander, Marju; Stumvoll, Michael; Tuomi, Tiinamaija; Pääbo, Svante; Koranyi, Laszlo; Groop, Leif.

I: Diabetologia, Vol. 59, Nr. 8, 08.2016, s. 1702-1713.

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Harvard

Prasad, RB, Lessmark, A, Almgren, P, Kovacs, G, Hansson, O, Oskolkov, N, Vitai, M, Ladenvall, C, Kovacs, P, Fadista, J, Lachmann, M, Zhou, Y, Sonestedt, E, Poon, W, Wollheim, CB, Orho-Melander, M, Stumvoll, M, Tuomi, T, Pääbo, S, Koranyi, L & Groop, L 2016, 'Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes', Diabetologia, vol. 59, nr. 8, s. 1702-1713. https://doi.org/10.1007/s00125-016-3973-9

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Prasad RB, Lessmark A, Almgren P, Kovacs G, Hansson O, Oskolkov N, Vitai M, Ladenvall C, Kovacs P, Fadista J, Lachmann M, Zhou Y, Sonestedt E, Poon W, Wollheim CB, Orho-Melander M, Stumvoll M, Tuomi T, Pääbo S, Koranyi L, Groop L. 2016. Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes. Diabetologia. 59(8):1702-1713. https://doi.org/10.1007/s00125-016-3973-9

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Prasad, Rashmi B. ; Lessmark, Anna ; Almgren, Peter ; Kovacs, Györgyi ; Hansson, Ola ; Oskolkov, Nikolay ; Vitai, Marta ; Ladenvall, Claes ; Kovacs, Peter ; Fadista, Joao ; Lachmann, Michael ; Zhou, Yuedan ; Sonestedt, Emily ; Poon, Wenny ; Wollheim, Claes B. ; Orho-Melander, Marju ; Stumvoll, Michael ; Tuomi, Tiinamaija ; Pääbo, Svante ; Koranyi, Laszlo ; Groop, Leif. / Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes. I: Diabetologia. 2016 ; Vol. 59, Nr. 8. s. 1702-1713.

RIS

TY - JOUR

T1 - Excess maternal transmission of variants in the THADA gene to offspring with type 2 diabetes

AU - Prasad, Rashmi B.

AU - Lessmark, Anna

AU - Almgren, Peter

AU - Kovacs, Györgyi

AU - Hansson, Ola

AU - Oskolkov, Nikolay

AU - Vitai, Marta

AU - Ladenvall, Claes

AU - Kovacs, Peter

AU - Fadista, Joao

AU - Lachmann, Michael

AU - Zhou, Yuedan

AU - Sonestedt, Emily

AU - Poon, Wenny

AU - Wollheim, Claes B.

AU - Orho-Melander, Marju

AU - Stumvoll, Michael

AU - Tuomi, Tiinamaija

AU - Pääbo, Svante

AU - Koranyi, Laszlo

AU - Groop, Leif

PY - 2016/8

Y1 - 2016/8

N2 - 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.

AB - 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.

KW - Families

KW - Genetic association studies

KW - KCNQ1

KW - Maternal effects

KW - Methylation

KW - Parent-of-origin

KW - Parental transmission

KW - THADA

KW - Type 2 diabetes

UR - http://www.scopus.com/inward/record.url?scp=84966354983&partnerID=8YFLogxK

U2 - 10.1007/s00125-016-3973-9

DO - 10.1007/s00125-016-3973-9

M3 - Article

VL - 59

SP - 1702

EP - 1713

JO - Diabetologia

T2 - Diabetologia

JF - Diabetologia

SN - 1432-0428

IS - 8

ER -