A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation.

Publication: Research - peer-reviewJournal article – Annual report year: 2012

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A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation.. / Dalgaard, Marlene D; Weinhold, Nils; Edsgard, Stefan Daniel; Silver, Jeremy D; Pers, Tune Hannes; Nielsen, John E.; Jørgensen, Niels; Juul, Anders; Gerds, Thomas A.; Giwercman, Aleksander; Giwercman, Yvonne L.; Cohn-Cedermark, Gabriella; Virtanen, Helena E.; Toppari, Jorma; Daugaard, Gedske; Jensen, Thomas Skøt; Brunak, Søren; Rajpert-De Meyts, Ewa; Skakkebæk, Niels E; Leffers, Henrik; Gupta, Ramneek.

In: Journal of Medical Genetics, Vol. 49, No. 1, 2012, p. 58-65.

Publication: Research - peer-reviewJournal article – Annual report year: 2012

Harvard

Dalgaard, MD, Weinhold, N, Edsgard, SD, Silver, JD, Pers, TH, Nielsen, JE, Jørgensen, N, Juul, A, Gerds, TA, Giwercman, A, Giwercman, YL, Cohn-Cedermark, G, Virtanen, HE, Toppari, J, Daugaard, G, Jensen, TS, Brunak, S, Rajpert-De Meyts, E, Skakkebæk, NE, Leffers, H & Gupta, R 2012, 'A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation.' Journal of Medical Genetics, vol 49, no. 1, pp. 58-65., 10.1136/jmedgenet-2011-100174

APA

CBE

Dalgaard MD, Weinhold N, Edsgard SD, Silver JD, Pers TH, Nielsen JE, Jørgensen N, Juul A, Gerds TA, Giwercman A, Giwercman YL, Cohn-Cedermark G, Virtanen HE, Toppari J, Daugaard G, Jensen TS, Brunak S, Rajpert-De Meyts E, Skakkebæk NE, Leffers H, Gupta R. 2012. A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation. Journal of Medical Genetics. 49(1):58-65. Available from: 10.1136/jmedgenet-2011-100174

MLA

Vancouver

Author

Dalgaard, Marlene D; Weinhold, Nils; Edsgard, Stefan Daniel; Silver, Jeremy D; Pers, Tune Hannes; Nielsen, John E.; Jørgensen, Niels; Juul, Anders; Gerds, Thomas A.; Giwercman, Aleksander; Giwercman, Yvonne L.; Cohn-Cedermark, Gabriella; Virtanen, Helena E.; Toppari, Jorma; Daugaard, Gedske; Jensen, Thomas Skøt; Brunak, Søren; Rajpert-De Meyts, Ewa; Skakkebæk, Niels E; Leffers, Henrik; Gupta, Ramneek / A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation..

In: Journal of Medical Genetics, Vol. 49, No. 1, 2012, p. 58-65.

Publication: Research - peer-reviewJournal article – Annual report year: 2012

Bibtex

@article{2ed0cf65db9c4316afa78742a013ff30,
title = "A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation.",
publisher = "B M J Group",
author = "Dalgaard, {Marlene D} and Nils Weinhold and Edsgard, {Stefan Daniel} and Silver, {Jeremy D} and Pers, {Tune Hannes} and Nielsen, {John E.} and Niels Jørgensen and Anders Juul and Gerds, {Thomas A.} and Aleksander Giwercman and Giwercman, {Yvonne L.} and Gabriella Cohn-Cedermark and Virtanen, {Helena E.} and Jorma Toppari and Gedske Daugaard and Jensen, {Thomas Skøt} and Søren Brunak and {Rajpert-De Meyts}, Ewa and Skakkebæk, {Niels E} and Henrik Leffers and Ramneek Gupta",
year = "2012",
doi = "10.1136/jmedgenet-2011-100174",
volume = "49",
number = "1",
pages = "58--65",
journal = "Journal of Medical Genetics",
issn = "0022-2593",

}

RIS

TY - JOUR

T1 - A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation.

A1 - Dalgaard,Marlene D

A1 - Weinhold,Nils

A1 - Edsgard,Stefan Daniel

A1 - Silver,Jeremy D

A1 - Pers,Tune Hannes

A1 - Nielsen,John E.

A1 - Jørgensen,Niels

A1 - Juul,Anders

A1 - Gerds,Thomas A.

A1 - Giwercman,Aleksander

A1 - Giwercman,Yvonne L.

A1 - Cohn-Cedermark,Gabriella

A1 - Virtanen,Helena E.

A1 - Toppari,Jorma

A1 - Daugaard,Gedske

A1 - Jensen,Thomas Skøt

A1 - Brunak,Søren

A1 - Rajpert-De Meyts,Ewa

A1 - Skakkebæk,Niels E

A1 - Leffers,Henrik

A1 - Gupta,Ramneek

AU - Dalgaard,Marlene D

AU - Weinhold,Nils

AU - Edsgard,Stefan Daniel

AU - Silver,Jeremy D

AU - Pers,Tune Hannes

AU - Nielsen,John E.

AU - Jørgensen,Niels

AU - Juul,Anders

AU - Gerds,Thomas A.

AU - Giwercman,Aleksander

AU - Giwercman,Yvonne L.

AU - Cohn-Cedermark,Gabriella

AU - Virtanen,Helena E.

AU - Toppari,Jorma

AU - Daugaard,Gedske

AU - Jensen,Thomas Skøt

AU - Brunak,Søren

AU - Rajpert-De Meyts,Ewa

AU - Skakkebæk,Niels E

AU - Leffers,Henrik

AU - Gupta,Ramneek

PB - B M J Group

PY - 2012

Y1 - 2012

N2 - Background Testicular dysgenesis syndrome (TDS) is a common disease that links testicular germ cell cancer, cryptorchidism and some cases of hypospadias and male infertility with impaired development of the testis. The incidence of these disorders has increased over the last few decades, and testicular cancer now affects 1% of the Danish and Norwegian male population. Methods To identify genetic variants that span the four TDS phenotypes, the authors performed a genome-wide association study (GWAS) using Affymetrix Human SNP Array 6.0 to screen 488 patients with symptoms of TDS and 439 selected controls with excellent reproductive health. Furthermore, they developed a novel integrative method that combines GWAS data with other TDS-relevant data types and identified additional TDS markers. The most significant findings were replicated in an independent cohort of 671 Nordic men. Results Markers located in the region of TGFBR3 and BMP7 showed association with all TDS phenotypes in both the discovery and replication cohorts. An immunohistochemistry investigation confirmed the presence of transforming growth factor β receptor type III (TGFBR3) in peritubular and Leydig cells, in both fetal and adult testis. Single-nucleotide polymorphisms in the KITLG gene showed significant associations, but only with testicular cancer. Conclusions The association of single-nucleotide polymorphisms in the TGFBR3 and BMP7 genes, which belong to the transforming growth factor β signalling pathway, suggests a role for this pathway in the pathogenesis of TDS. Integrating data from multiple layers can highlight findings in GWAS that are biologically relevant despite having border significance at currently accepted statistical levels.

AB - Background Testicular dysgenesis syndrome (TDS) is a common disease that links testicular germ cell cancer, cryptorchidism and some cases of hypospadias and male infertility with impaired development of the testis. The incidence of these disorders has increased over the last few decades, and testicular cancer now affects 1% of the Danish and Norwegian male population. Methods To identify genetic variants that span the four TDS phenotypes, the authors performed a genome-wide association study (GWAS) using Affymetrix Human SNP Array 6.0 to screen 488 patients with symptoms of TDS and 439 selected controls with excellent reproductive health. Furthermore, they developed a novel integrative method that combines GWAS data with other TDS-relevant data types and identified additional TDS markers. The most significant findings were replicated in an independent cohort of 671 Nordic men. Results Markers located in the region of TGFBR3 and BMP7 showed association with all TDS phenotypes in both the discovery and replication cohorts. An immunohistochemistry investigation confirmed the presence of transforming growth factor β receptor type III (TGFBR3) in peritubular and Leydig cells, in both fetal and adult testis. Single-nucleotide polymorphisms in the KITLG gene showed significant associations, but only with testicular cancer. Conclusions The association of single-nucleotide polymorphisms in the TGFBR3 and BMP7 genes, which belong to the transforming growth factor β signalling pathway, suggests a role for this pathway in the pathogenesis of TDS. Integrating data from multiple layers can highlight findings in GWAS that are biologically relevant despite having border significance at currently accepted statistical levels.

U2 - 10.1136/jmedgenet-2011-100174

DO - 10.1136/jmedgenet-2011-100174

JO - Journal of Medical Genetics

JF - Journal of Medical Genetics

SN - 0022-2593

IS - 1

VL - 49

SP - 58

EP - 65

ER -