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Discovery of sexual dimorphisms in metabolic and genetic biomarkers
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نویسنده
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mittelstrass k. ,ried j.s. ,yu z. ,krumsiek j. ,gieger c. ,prehn c. ,roemisch-margl w. ,polonikov a. ,peters a. ,theis f.j. ,meitinger t. ,kronenberg f. ,weidinger s. ,wichmann h.e. ,suhre k. ,wang-sattler r. ,adamski j. ,illig t.
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منبع
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plos genetics - 2011 - دوره : 7 - شماره : 8
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چکیده
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Metabolomic profiling and the integration of whole-genome genetic association data has proven to be a powerful tool to comprehensively explore gene regulatory networks and to investigate the effects of genetic variation at the molecular level. serum metabolite concentrations allow a direct readout of biological processes,and association of specific metabolomic signatures with complex diseases such as alzheimer's disease and cardiovascular and metabolic disorders has been shown. there are well-known correlations between sex and the incidence,prevalence,age of onset,symptoms,and severity of a disease,as well as the reaction to drugs. however,most of the studies published so far did not consider the role of sexual dimorphism and did not analyse their data stratified by gender. this study investigated sex-specific differences of serum metabolite concentrations and their underlying genetic determination. for discovery and replication we used more than 3,300 independent individuals from kora f3 and f4 with metabolite measurements of 131 metabolites,including amino acids,phosphatidylcholines,sphingomyelins,acylcarnitines,and c6-sugars. a linear regression approach revealed significant concentration differences between males and females for 102 out of 131 metabolites (p-values<3.8×10 -4; bonferroni-corrected threshold). sex-specific genome-wide association studies (gwas) showed genome-wide significant differences in beta-estimates for snps in the cps1 locus (carbamoyl-phosphate synthase 1,significance level: p<3.8×10 -10; bonferroni-corrected threshold) for glycine. we showed that the metabolite profiles of males and females are significantly different and,furthermore,that specific genetic variants in metabolism-related genes depict sexual dimorphism. our study provides new important insights into sex-specific differences of cell regulatory processes and underscores that studies should consider sex-specific effects in design and interpretation. © 2011 mittelstrass et al.
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آدرس
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unit of molecular epidemiology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of genetic epidemiology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, unit of molecular epidemiology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of bioinformatics and systems biology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of genetic epidemiology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of experimental genetics,genome analysis center,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of bioinformatics and systems biology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, department of biology,medical genetics,and ecology,kursk state medical university,kursk, Russian Federation, institute of epidemiology ii,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of bioinformatics and systems biology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of human genetics,helmholtz center munich,german research center for environmental health,neuherberg,germany,institute of human genetics,klinikum rechts der isar,technische universität münchen,munich, Germany, division of genetic epidemiology,department of medical genetics and molecular and clinical pharmacology,innsbruck medical university,innsbruck, Austria, department of dermatology,venereology,and allergy,university hospital schleswig-holstein,kiel, Germany, institute of epidemiology i,helmholtz center munich,german research center for environmental health,neuherberg,germany,institute of medical informatics,biometry,and epidemiology,chair of epidemiology,ludwig-maximilians-universität,munich,germany,klinikum grosshadern,munich, Germany, institute of bioinformatics and systems biology,helmholtz center munich,german research center for environmental health,neuherberg,germany,faculty of biology,ludwig-maximilians-universität,planegg-martinsried,germany,weill cornell medical college in qatar,qatar foundation,education city,doha, Qatar, unit of molecular epidemiology,helmholtz center munich,german research center for environmental health,neuherberg, Germany, institute of experimental genetics,genome analysis center,helmholtz center munich,german research center for environmental health,neuherberg,germany,lehrstuhl für experimentelle genetik,technische universität münchen,munich, Germany, unit of molecular epidemiology,helmholtz center munich,german research center for environmental health,neuherberg, Germany
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Authors
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