Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits
The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. We enrolled 2632 Japanese sub...
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| Veröffentlicht in: | Journal of human genetics 2012-12, Vol.57 (12), p.776-779 |
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| container_title | Journal of human genetics |
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| creator | Fujita, Hayato Hara, Kazuo Shojima, Nobuhiro Horikoshi, Momoko Iwata, Minoru Hirota, Yushi Tobe, Kazuyuki Seino, Susumu Kadowaki, Takashi |
| description | The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. We enrolled 2632 Japanese subjects with T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349 (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1), rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and rs174550 (FADS1) were significantly associated with T2D (P=0.0078, OR: 1.12; and P=0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to nine SNPs had an increased risk of T2D (P=0.0017), as well as a higher fasting plasma glucose level (P=0.018), higher HbA(1c) level (P=0.013) and lower HOMA-β (P=0.033) compared with subjects who had fewer risk alleles. We identified a significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a Japanese population. The present findings suggest that inclusion of SNPs with a tendency to increase the disease risk captured more of the genetic background of T2D than that revealed by only assessing significant SNPs. |
| doi_str_mv | 10.1038/jhg.2012.110 |
| format | Article |
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We enrolled 2632 Japanese subjects with T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349 (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1), rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and rs174550 (FADS1) were significantly associated with T2D (P=0.0078, OR: 1.12; and P=0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to nine SNPs had an increased risk of T2D (P=0.0017), as well as a higher fasting plasma glucose level (P=0.018), higher HbA(1c) level (P=0.013) and lower HOMA-β (P=0.033) compared with subjects who had fewer risk alleles. We identified a significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a Japanese population. The present findings suggest that inclusion of SNPs with a tendency to increase the disease risk captured more of the genetic background of T2D than that revealed by only assessing significant SNPs.</description><identifier>ISSN: 1434-5161</identifier><identifier>EISSN: 1435-232X</identifier><identifier>DOI: 10.1038/jhg.2012.110</identifier><identifier>PMID: 22992776</identifier><language>eng</language><publisher>England: Nature Publishing Group</publisher><subject>Aged ; Alleles ; Asian Continental Ancestry Group - genetics ; Biomarkers - analysis ; Blood Glucose - metabolism ; Case-Control Studies ; Diabetes ; Diabetes mellitus (non-insulin dependent) ; Diabetes Mellitus, Type 2 - genetics ; Diabetes Mellitus, Type 2 - metabolism ; Female ; Genetic Predisposition to Disease ; Genome-Wide Association Study ; Genotype ; Humans ; Insulin - metabolism ; Insulin-like growth factor I ; Middle Aged ; Phenotype ; Polymorphism, Single Nucleotide - genetics ; Population genetics ; Risk Factors ; Single-nucleotide polymorphism</subject><ispartof>Journal of human genetics, 2012-12, Vol.57 (12), p.776-779</ispartof><rights>The Japan Society of Human Genetics 2012.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c414t-93709a83c31f7a8ba6bc9ae0fedd75058b3c6898acdb822e3c8fd39dae8e4a1b3</citedby><cites>FETCH-LOGICAL-c414t-93709a83c31f7a8ba6bc9ae0fedd75058b3c6898acdb822e3c8fd39dae8e4a1b3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22992776$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Fujita, Hayato</creatorcontrib><creatorcontrib>Hara, Kazuo</creatorcontrib><creatorcontrib>Shojima, Nobuhiro</creatorcontrib><creatorcontrib>Horikoshi, Momoko</creatorcontrib><creatorcontrib>Iwata, Minoru</creatorcontrib><creatorcontrib>Hirota, Yushi</creatorcontrib><creatorcontrib>Tobe, Kazuyuki</creatorcontrib><creatorcontrib>Seino, Susumu</creatorcontrib><creatorcontrib>Kadowaki, Takashi</creatorcontrib><title>Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits</title><title>Journal of human genetics</title><addtitle>J Hum Genet</addtitle><description>The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. 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Academic</collection><jtitle>Journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Fujita, Hayato</au><au>Hara, Kazuo</au><au>Shojima, Nobuhiro</au><au>Horikoshi, Momoko</au><au>Iwata, Minoru</au><au>Hirota, Yushi</au><au>Tobe, Kazuyuki</au><au>Seino, Susumu</au><au>Kadowaki, Takashi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits</atitle><jtitle>Journal of human genetics</jtitle><addtitle>J Hum Genet</addtitle><date>2012-12-01</date><risdate>2012</risdate><volume>57</volume><issue>12</issue><spage>776</spage><epage>779</epage><pages>776-779</pages><issn>1434-5161</issn><eissn>1435-232X</eissn><abstract>The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. We enrolled 2632 Japanese subjects with T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349 (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1), rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and rs174550 (FADS1) were significantly associated with T2D (P=0.0078, OR: 1.12; and P=0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to nine SNPs had an increased risk of T2D (P=0.0017), as well as a higher fasting plasma glucose level (P=0.018), higher HbA(1c) level (P=0.013) and lower HOMA-β (P=0.033) compared with subjects who had fewer risk alleles. We identified a significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a Japanese population. The present findings suggest that inclusion of SNPs with a tendency to increase the disease risk captured more of the genetic background of T2D than that revealed by only assessing significant SNPs.</abstract><cop>England</cop><pub>Nature Publishing Group</pub><pmid>22992776</pmid><doi>10.1038/jhg.2012.110</doi><tpages>4</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Aged Alleles Asian Continental Ancestry Group - genetics Biomarkers - analysis Blood Glucose - metabolism Case-Control Studies Diabetes Diabetes mellitus (non-insulin dependent) Diabetes Mellitus, Type 2 - genetics Diabetes Mellitus, Type 2 - metabolism Female Genetic Predisposition to Disease Genome-Wide Association Study Genotype Humans Insulin - metabolism Insulin-like growth factor I Middle Aged Phenotype Polymorphism, Single Nucleotide - genetics Population genetics Risk Factors Single-nucleotide polymorphism |
| title | Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits |
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