Genetics play an important role in the
variation in, and risk of, low
testosterone concentrations in men. A
study by the CHARGE Sex Hormone
Consortium, published in the open-
access journal PLoS Genetics , is the
first genome-wide association study to
examine the effects of common
genetic variants on serum
testosterone concentrations in men.
Testosterone is the principal male sex
hormone and a potent anabolic
steroid. It exerts a variety of important
physiological effects on the human
body. Low testosterone
concentrations in men are associated
with increased risk of cardiovascular
morbidity, type 2 diabetes ,
atherosclerosis, osteoporosis,
metabolic syndrome, and sarcopenia.
Testosterone concentrations are
known to decrease with age, but the
observed inter-individual variability in
testosterone concentrations in men is
poorly understood.
By pooling the data of 14,429
Caucasian men, an international
collaboration of 10 independent
cohorts, co-led by the University of
Gothenburg and the University of
Greifswald, discovered genetic
variants at the sex hormone-binding
globulin (SHBG) gene and on the X
chromosome associated with an
increased risk of low testosterone.
Lead author Prof. Claes Ohlsson from
the University of Gothenburg says:
"This is the first large-scale study to
identify specific genes for low serum
testosterone concentrations. It is very
interesting that the genetic
contribution of the identified genetic
variants to testosterone
concentrations is substantial."
Co-senior author Dr. Robin Haring
from the University of Greifswald
concludes: "The reported associations
may now be used in order to better
understand the functional
background of recently identified
disease associations related to low
testosterone concentrations in men."
List of consortium members
The members of the consortium
include: The Framingham Heart Study
(FHS), Study of Health in Pomerania
(SHIP), The Gothenburg Osteoporosis
and Obesity Determinants (GOOD)
Study, Cooperative Research in the
Region of Augsburg (KORA), The
Health, Aging, and Body Composition
(Health ABC) Study, Rotterdam Study
baseline (RS1) , Invecchiare in Chianti
(InCHIANTI), European Male Ageing
Study (EMAS), The Osteoporotic
Fractures in Men Study - Sweden
(MrOS Sweden), The Cardiovascular
Risk in Young Finns Study (YFS) .
FINANCIAL DISCLOSURE
Framingham Heart Study (FHS): The
FHS phenotype- genotype analyses for
this work were supported by the
National Institute of Aging (Genetics of
Reproductive Life Period and Health
Outcomes, R21AG 032598; JM
Murabito, KL Lunetta, D Karasik, DP
Kiel, WV Zhuang). The Framingham
Heart Study of the National Heart
Lung and Blood Institute of the
National Institutes of Health and
Boston University School of Medicine
is supported by the National Heart,
Lung, and Blood Institute's
Framingham Heart Study Contract No.
N01- HC-25195 and its contract with
Affymetrix for genotyping services
(Contract No. N02-HL -6-4278 ). Sex
hormone measurements were funded
primarily by National Institute on
Aging grant 1RO1 AG31206 (PIs: S
Bhasin and RS Vasan); additional
support was provided by the Boston
Claude D. Pepper Older Americans
Independence Center
(5P 30AG031679 ) and a grant from the
National Institute on Aging and the
National Institute of Arthritis
Musculoskeletal and Skin Diseases to
DP Kiel (R01 AR/AG 41398). Analyses
reflect intellectual input and resource
development from the Framingham
Heart Study investigators participating
in the SNP Health Association
Resource (SHARe) project. A portion
of this research was conducted using
the Linux Cluster for Genetic Analysis
(LinGA-II ), funded by the Robert
Dawson Evans Endowment of the
Department of Medicine at Boston
University School of Medicine and
Boston Medical Center. Study of
Health in Pomerania (SHIP) :
Computing resources have been
made available by the Leibniz
Supercomputing Centre of the
Bavarian Academy of Sciences and
Humanities (HLRB project h1231 ).
SHIP is part of the Community
Medicine Research net of the
University of Greifswald, Germany,
which is funded by the Federal
Ministry of Education and Research
(grants no. 01ZZ9603, 01ZZ0103, and
01ZZ0403) , the Ministry of Cultural
Affairs as well as the Social Ministry of
the Federal State of Mecklenburg -
West Pomerania. Genome- wide data
have been supported by the Federal
Ministry of Education and Research
(grant no. 03ZIK012 ) and a joint grant
from Siemens Healthcare, Erlangen,
Germany, and the Federal State of
Mecklenburg West Pomerania. The
University of Greifswald is a member
of the ''Center of Knowledge
Interchange'' program of the Siemens
AG. This work is also part of the
research project Greifswald Approach
to Individualized Medicine
(GANI_ MED). The GANI_MED
consortium is funded by the Federal
Ministry of Education and Research
and the Ministry of Cultural Affairs of
the Federal State of Mecklenburg -
West Pomerania (03IS2061A ). The
testosterone reagents used were
sponsored by Siemens Healthcare
Diagnostics, Eschborn, formerly DPC
Biermann GmbH, Bad Nauheim,
Germany. Novo Nordisc provided
partial grant support for the
determination of serum samples and
data analysis. Gothenburg
Osteoporosis and Obesity
Determinants (GOOD) Study: Financial
support was received from the
Swedish Research Council
(K2010 -54X- 09894-19-3 , 2006-3832 ,
and K2010 -52X- 20229-05-3 ), the
Swedish Foundation for Strategic
Research, the ALF/LUA research grant
in Gothenburg, the Lundberg
Foundation, the Torsten and Ragnar
So¨derberg 's Foundation, Petrus and
Augusta Hedlunds Foundation, the
Va¨stra Go¨ taland Foundation, the
Go¨ teborg Medical Society, the Novo
Nordisk foundation, the Canadian
Institutes of Health Research
(MOP-15261 ), and the European
Commission grant HEALTH-
F2- 2008-201865 -GEFOS. We would like
to acknowledge Maria Nethander at
the genomics core facility at University
of Gothenburg for statistical analyses.
We would also like to thank Dr. Tobias
A. Knoch, Luc V. de Zeeuw, Anis
Abuseiris, and Rob de Graaf as well as
their institutions the Erasmus
Computing Grid, Rotterdam, The
Netherlands, and especially the
national GermanMediGRID and
Services@MediGRID part of the
German D-Grid, both funded by the
German Bundesministerium fuer
Forschung und Technology under
grants #01 AK 803 A-H and # 01 IG
07015 G for access to their grid
resources. Cooperative Research in
the Region of Augsburg (KORA): The
KORA research platform was initiated
and financed by the Helmholtz Center
Munich, German Research Center for
Environmental Health, which is
funded by the German Federal
Ministry of Education and Research
(BMBF) and by the State of Bavaria.
Part of this work was financed by the
German National Genome Research
Network (NGFN-2 and NGFNPlus:
01GS0823) . Our research was
supported within the Munich Center
of Health Sciences (MC Health) as part
of LMUinnovativ. This study was in
part supported by a grant from the
German Federal Ministry of Education
and Research (BMBF) to the German
Center for Diabetes Research (DZD
e.V .). Health, Aging, and Body
Composition (Health ABC) Study: This
study was supported by National
Institute on Aging contracts N01-
AG-6 -2101, N01 -AG-6 -2103, and N01-
AG-6 -2106. The genome-wide
association study was funded by NIA
grant 1R 01AG032098 -01A1 to Wake
Forest University Health Sciences and
genotyping services were provided by
the Center for Inherited Disease
Research (CIDR) . CIDR is fully funded
through a federal contract from the
National Institutes of Health to The
Johns Hopkins University, contract
number HHSN268200782096C. This
research was supported (in part) by
the Intramural Research Program of
the NIH, National Institute on Aging.
Rotterdam study (RS1 ): The
generation and management of GWAS
genotype data for the Rotterdam
Study is supported by the Netherlands
Organisation of Scientific Research
NWO Investments (nr.
175.010 .2005. 011, 911- 03-012) . This
study is funded by the Research
Institute for Diseases in the Elderly
(014- 93-015 ; RIDE2) , the Netherlands
Genomics Initiative (NGI) -
Netherlands Consortiumof Healthy
Aging (NCHA) project nr. 050- 060-810 ,
and funding fromthe European
Commision (HEALTH-F2 -2008-201865 ,
GEFOS; HEALTH-F2 -2008- 35627,
TREAT-OA ). The RotterdamStudy is
funded by Erasmus Medical Center
and Erasmus University Rotterdam;
Netherlands Organisation for Health
Research and Development (ZonMw);
the Research Institute for Diseases in
the Elderly (RIDE); the Ministry of
Education, Culture, and Science; the
Ministry for Health, Welfare, and
Sports; the European Commission
(DG XII); and the Municipality of
Rotterdam. We thank Pascal Arp, Mila
Jhamai, Dr. Michael Moorhouse,
Marijn Verkerk, and Sander Bervoets
for their help in creating the GWAS
database. The authors are grateful to
the study participants, the staff from
the Rotterdam Study, and the
participating general practioners and
pharmacists. We would like to thank
Dr. Tobias A. Knoch, Luc V. de Zeeuw,
Anis Abuseiris, and Rob de Graaf as
well as
variation in, and risk of, low
testosterone concentrations in men. A
study by the CHARGE Sex Hormone
Consortium, published in the open-
access journal PLoS Genetics , is the
first genome-wide association study to
examine the effects of common
genetic variants on serum
testosterone concentrations in men.
Testosterone is the principal male sex
hormone and a potent anabolic
steroid. It exerts a variety of important
physiological effects on the human
body. Low testosterone
concentrations in men are associated
with increased risk of cardiovascular
morbidity, type 2 diabetes ,
atherosclerosis, osteoporosis,
metabolic syndrome, and sarcopenia.
Testosterone concentrations are
known to decrease with age, but the
observed inter-individual variability in
testosterone concentrations in men is
poorly understood.
By pooling the data of 14,429
Caucasian men, an international
collaboration of 10 independent
cohorts, co-led by the University of
Gothenburg and the University of
Greifswald, discovered genetic
variants at the sex hormone-binding
globulin (SHBG) gene and on the X
chromosome associated with an
increased risk of low testosterone.
Lead author Prof. Claes Ohlsson from
the University of Gothenburg says:
"This is the first large-scale study to
identify specific genes for low serum
testosterone concentrations. It is very
interesting that the genetic
contribution of the identified genetic
variants to testosterone
concentrations is substantial."
Co-senior author Dr. Robin Haring
from the University of Greifswald
concludes: "The reported associations
may now be used in order to better
understand the functional
background of recently identified
disease associations related to low
testosterone concentrations in men."
List of consortium members
The members of the consortium
include: The Framingham Heart Study
(FHS), Study of Health in Pomerania
(SHIP), The Gothenburg Osteoporosis
and Obesity Determinants (GOOD)
Study, Cooperative Research in the
Region of Augsburg (KORA), The
Health, Aging, and Body Composition
(Health ABC) Study, Rotterdam Study
baseline (RS1) , Invecchiare in Chianti
(InCHIANTI), European Male Ageing
Study (EMAS), The Osteoporotic
Fractures in Men Study - Sweden
(MrOS Sweden), The Cardiovascular
Risk in Young Finns Study (YFS) .
FINANCIAL DISCLOSURE
Framingham Heart Study (FHS): The
FHS phenotype- genotype analyses for
this work were supported by the
National Institute of Aging (Genetics of
Reproductive Life Period and Health
Outcomes, R21AG 032598; JM
Murabito, KL Lunetta, D Karasik, DP
Kiel, WV Zhuang). The Framingham
Heart Study of the National Heart
Lung and Blood Institute of the
National Institutes of Health and
Boston University School of Medicine
is supported by the National Heart,
Lung, and Blood Institute's
Framingham Heart Study Contract No.
N01- HC-25195 and its contract with
Affymetrix for genotyping services
(Contract No. N02-HL -6-4278 ). Sex
hormone measurements were funded
primarily by National Institute on
Aging grant 1RO1 AG31206 (PIs: S
Bhasin and RS Vasan); additional
support was provided by the Boston
Claude D. Pepper Older Americans
Independence Center
(5P 30AG031679 ) and a grant from the
National Institute on Aging and the
National Institute of Arthritis
Musculoskeletal and Skin Diseases to
DP Kiel (R01 AR/AG 41398). Analyses
reflect intellectual input and resource
development from the Framingham
Heart Study investigators participating
in the SNP Health Association
Resource (SHARe) project. A portion
of this research was conducted using
the Linux Cluster for Genetic Analysis
(LinGA-II ), funded by the Robert
Dawson Evans Endowment of the
Department of Medicine at Boston
University School of Medicine and
Boston Medical Center. Study of
Health in Pomerania (SHIP) :
Computing resources have been
made available by the Leibniz
Supercomputing Centre of the
Bavarian Academy of Sciences and
Humanities (HLRB project h1231 ).
SHIP is part of the Community
Medicine Research net of the
University of Greifswald, Germany,
which is funded by the Federal
Ministry of Education and Research
(grants no. 01ZZ9603, 01ZZ0103, and
01ZZ0403) , the Ministry of Cultural
Affairs as well as the Social Ministry of
the Federal State of Mecklenburg -
West Pomerania. Genome- wide data
have been supported by the Federal
Ministry of Education and Research
(grant no. 03ZIK012 ) and a joint grant
from Siemens Healthcare, Erlangen,
Germany, and the Federal State of
Mecklenburg West Pomerania. The
University of Greifswald is a member
of the ''Center of Knowledge
Interchange'' program of the Siemens
AG. This work is also part of the
research project Greifswald Approach
to Individualized Medicine
(GANI_ MED). The GANI_MED
consortium is funded by the Federal
Ministry of Education and Research
and the Ministry of Cultural Affairs of
the Federal State of Mecklenburg -
West Pomerania (03IS2061A ). The
testosterone reagents used were
sponsored by Siemens Healthcare
Diagnostics, Eschborn, formerly DPC
Biermann GmbH, Bad Nauheim,
Germany. Novo Nordisc provided
partial grant support for the
determination of serum samples and
data analysis. Gothenburg
Osteoporosis and Obesity
Determinants (GOOD) Study: Financial
support was received from the
Swedish Research Council
(K2010 -54X- 09894-19-3 , 2006-3832 ,
and K2010 -52X- 20229-05-3 ), the
Swedish Foundation for Strategic
Research, the ALF/LUA research grant
in Gothenburg, the Lundberg
Foundation, the Torsten and Ragnar
So¨derberg 's Foundation, Petrus and
Augusta Hedlunds Foundation, the
Va¨stra Go¨ taland Foundation, the
Go¨ teborg Medical Society, the Novo
Nordisk foundation, the Canadian
Institutes of Health Research
(MOP-15261 ), and the European
Commission grant HEALTH-
F2- 2008-201865 -GEFOS. We would like
to acknowledge Maria Nethander at
the genomics core facility at University
of Gothenburg for statistical analyses.
We would also like to thank Dr. Tobias
A. Knoch, Luc V. de Zeeuw, Anis
Abuseiris, and Rob de Graaf as well as
their institutions the Erasmus
Computing Grid, Rotterdam, The
Netherlands, and especially the
national GermanMediGRID and
Services@MediGRID part of the
German D-Grid, both funded by the
German Bundesministerium fuer
Forschung und Technology under
grants #01 AK 803 A-H and # 01 IG
07015 G for access to their grid
resources. Cooperative Research in
the Region of Augsburg (KORA): The
KORA research platform was initiated
and financed by the Helmholtz Center
Munich, German Research Center for
Environmental Health, which is
funded by the German Federal
Ministry of Education and Research
(BMBF) and by the State of Bavaria.
Part of this work was financed by the
German National Genome Research
Network (NGFN-2 and NGFNPlus:
01GS0823) . Our research was
supported within the Munich Center
of Health Sciences (MC Health) as part
of LMUinnovativ. This study was in
part supported by a grant from the
German Federal Ministry of Education
and Research (BMBF) to the German
Center for Diabetes Research (DZD
e.V .). Health, Aging, and Body
Composition (Health ABC) Study: This
study was supported by National
Institute on Aging contracts N01-
AG-6 -2101, N01 -AG-6 -2103, and N01-
AG-6 -2106. The genome-wide
association study was funded by NIA
grant 1R 01AG032098 -01A1 to Wake
Forest University Health Sciences and
genotyping services were provided by
the Center for Inherited Disease
Research (CIDR) . CIDR is fully funded
through a federal contract from the
National Institutes of Health to The
Johns Hopkins University, contract
number HHSN268200782096C. This
research was supported (in part) by
the Intramural Research Program of
the NIH, National Institute on Aging.
Rotterdam study (RS1 ): The
generation and management of GWAS
genotype data for the Rotterdam
Study is supported by the Netherlands
Organisation of Scientific Research
NWO Investments (nr.
175.010 .2005. 011, 911- 03-012) . This
study is funded by the Research
Institute for Diseases in the Elderly
(014- 93-015 ; RIDE2) , the Netherlands
Genomics Initiative (NGI) -
Netherlands Consortiumof Healthy
Aging (NCHA) project nr. 050- 060-810 ,
and funding fromthe European
Commision (HEALTH-F2 -2008-201865 ,
GEFOS; HEALTH-F2 -2008- 35627,
TREAT-OA ). The RotterdamStudy is
funded by Erasmus Medical Center
and Erasmus University Rotterdam;
Netherlands Organisation for Health
Research and Development (ZonMw);
the Research Institute for Diseases in
the Elderly (RIDE); the Ministry of
Education, Culture, and Science; the
Ministry for Health, Welfare, and
Sports; the European Commission
(DG XII); and the Municipality of
Rotterdam. We thank Pascal Arp, Mila
Jhamai, Dr. Michael Moorhouse,
Marijn Verkerk, and Sander Bervoets
for their help in creating the GWAS
database. The authors are grateful to
the study participants, the staff from
the Rotterdam Study, and the
participating general practioners and
pharmacists. We would like to thank
Dr. Tobias A. Knoch, Luc V. de Zeeuw,
Anis Abuseiris, and Rob de Graaf as
well as
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