Variance-Component Analysis of Obesity in Type 2 Diabetes Confirms Loci on Chromosomes 1q and 11q
To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome‐wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of ∼75% covering all 22 autosomes. Genotype data were obtained from 562 individuals fro...
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Veröffentlicht in: | Obesity (Silver Spring, Md.) Md.), 2003-11, Vol.11 (11), p.1290-1294 |
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creator | Tilburg, Jonathan H.O. Sandkuijl, Lodewijk A. Strengman, Eric Pearson, Peter L. Haeften, Timon W. Wijmenga, Cisca |
description | To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome‐wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of ∼75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores ≥1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine‐mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31‐q42 and 11q14‐q24. |
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Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores ≥1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine‐mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31‐q42 and 11q14‐q24.</description><identifier>ISSN: 1930-7381</identifier><identifier>ISSN: 1071-7323</identifier><identifier>EISSN: 1930-739X</identifier><identifier>EISSN: 1550-8528</identifier><identifier>DOI: 10.1038/oby.2003.175</identifier><identifier>PMID: 14627748</identifier><language>eng</language><publisher>Oxford, UK: Blackwell Publishing Ltd</publisher><subject>Aged ; Analysis of Variance ; Body Mass Index ; Chromosomes, Human, Pair 1 ; Chromosomes, Human, Pair 11 ; Diabetes Mellitus - genetics ; Diabetes Mellitus, Type 2 - genetics ; Female ; genetics ; genome‐wide screening ; Genotype ; Heterozygote ; Humans ; Lod Score ; Male ; Microsatellite Repeats ; Middle Aged ; Obesity ; Quantitative Trait Loci ; type 2 diabetes</subject><ispartof>Obesity (Silver Spring, Md.), 2003-11, Vol.11 (11), p.1290-1294</ispartof><rights>2003 North American Association for the Study of Obesity (NAASO)</rights><rights>Copyright Nature Publishing Group Nov 2003</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4194-4046f6898506dc09bfee6000e3ecb552cbb66893febdf24e690d89788c3a70a23</citedby><cites>FETCH-LOGICAL-c4194-4046f6898506dc09bfee6000e3ecb552cbb66893febdf24e690d89788c3a70a23</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1038%2Foby.2003.175$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1038%2Foby.2003.175$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>315,781,785,1418,1434,27925,27926,45575,45576,46410,46834</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/14627748$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Tilburg, Jonathan H.O.</creatorcontrib><creatorcontrib>Sandkuijl, Lodewijk A.</creatorcontrib><creatorcontrib>Strengman, Eric</creatorcontrib><creatorcontrib>Pearson, Peter L.</creatorcontrib><creatorcontrib>Haeften, Timon W.</creatorcontrib><creatorcontrib>Wijmenga, Cisca</creatorcontrib><title>Variance-Component Analysis of Obesity in Type 2 Diabetes Confirms Loci on Chromosomes 1q and 11q</title><title>Obesity (Silver Spring, Md.)</title><addtitle>Obes Res</addtitle><description>To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome‐wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of ∼75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores ≥1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine‐mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. Our study to determine linkage for BMI confirms the presence of quantitative trait loci influencing obesity in subjects with type 2 diabetes on chromosomes 1q31‐q42 and 11q14‐q24.</description><subject>Aged</subject><subject>Analysis of Variance</subject><subject>Body Mass Index</subject><subject>Chromosomes, Human, Pair 1</subject><subject>Chromosomes, Human, Pair 11</subject><subject>Diabetes Mellitus - genetics</subject><subject>Diabetes Mellitus, Type 2 - genetics</subject><subject>Female</subject><subject>genetics</subject><subject>genome‐wide screening</subject><subject>Genotype</subject><subject>Heterozygote</subject><subject>Humans</subject><subject>Lod Score</subject><subject>Male</subject><subject>Microsatellite Repeats</subject><subject>Middle Aged</subject><subject>Obesity</subject><subject>Quantitative Trait Loci</subject><subject>type 2 diabetes</subject><issn>1930-7381</issn><issn>1071-7323</issn><issn>1930-739X</issn><issn>1550-8528</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2003</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp90EFrHCEUB3ApDU2a5NZzEQo5dTY6Ouoc00nbFBb2koTkNKjzhhpmdFdnKPPt67JLCj3kpPB-7_n8I_SJkhUlTF0Hs6xKQtiKyuodOqM1I4Vk9dP717uip-hjSi-EcEEq-gGdUi5KKbk6Q_pRR6e9haIJ4zZ48BO-8XpYkks49HhjILlpwc7j-2ULuMS3ThuYIOEm-N7FMeF1sA4Hj5vfMYwhhTEX6Q5r32FKdxfopNdDgsvjeY4efny_b-6K9ebnr-ZmXVhOa17wvFwvVK0qIjpLatMDCEIIMLCmqkprjMhl1oPp-pKDqEmnaqmUZVoSXbJzdHWYu41hN0Oa2tElC8OgPYQ5tZIyVQtGM_zyH3wJc8x_Tm0OlEihlJRZfT0oG0NKEfp2G92o45LR3qk2B9_ug29z8Jl_Pg6dzQjdP3xMOgNyAH_cAMubw9rNt2fJeW7BhxavpznCa0-2e7p_9i-A8pbW</recordid><startdate>200311</startdate><enddate>200311</enddate><creator>Tilburg, Jonathan H.O.</creator><creator>Sandkuijl, Lodewijk A.</creator><creator>Strengman, Eric</creator><creator>Pearson, Peter L.</creator><creator>Haeften, Timon W.</creator><creator>Wijmenga, Cisca</creator><general>Blackwell Publishing Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>K9.</scope><scope>7X8</scope></search><sort><creationdate>200311</creationdate><title>Variance-Component Analysis of Obesity in Type 2 Diabetes Confirms Loci on Chromosomes 1q and 11q</title><author>Tilburg, Jonathan H.O. ; Sandkuijl, Lodewijk A. ; Strengman, Eric ; Pearson, Peter L. ; Haeften, Timon W. ; Wijmenga, Cisca</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4194-4046f6898506dc09bfee6000e3ecb552cbb66893febdf24e690d89788c3a70a23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2003</creationdate><topic>Aged</topic><topic>Analysis of Variance</topic><topic>Body Mass Index</topic><topic>Chromosomes, Human, Pair 1</topic><topic>Chromosomes, Human, Pair 11</topic><topic>Diabetes Mellitus - genetics</topic><topic>Diabetes Mellitus, Type 2 - genetics</topic><topic>Female</topic><topic>genetics</topic><topic>genome‐wide screening</topic><topic>Genotype</topic><topic>Heterozygote</topic><topic>Humans</topic><topic>Lod Score</topic><topic>Male</topic><topic>Microsatellite Repeats</topic><topic>Middle Aged</topic><topic>Obesity</topic><topic>Quantitative Trait Loci</topic><topic>type 2 diabetes</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Tilburg, Jonathan H.O.</creatorcontrib><creatorcontrib>Sandkuijl, Lodewijk A.</creatorcontrib><creatorcontrib>Strengman, Eric</creatorcontrib><creatorcontrib>Pearson, Peter L.</creatorcontrib><creatorcontrib>Haeften, Timon W.</creatorcontrib><creatorcontrib>Wijmenga, Cisca</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><jtitle>Obesity (Silver Spring, Md.)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Tilburg, Jonathan H.O.</au><au>Sandkuijl, Lodewijk A.</au><au>Strengman, Eric</au><au>Pearson, Peter L.</au><au>Haeften, Timon W.</au><au>Wijmenga, Cisca</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Variance-Component Analysis of Obesity in Type 2 Diabetes Confirms Loci on Chromosomes 1q and 11q</atitle><jtitle>Obesity (Silver Spring, Md.)</jtitle><addtitle>Obes Res</addtitle><date>2003-11</date><risdate>2003</risdate><volume>11</volume><issue>11</issue><spage>1290</spage><epage>1294</epage><pages>1290-1294</pages><issn>1930-7381</issn><issn>1071-7323</issn><eissn>1930-739X</eissn><eissn>1550-8528</eissn><abstract>To study genetic loci influencing obesity in nuclear families with type 2 diabetes, we performed a genome‐wide screen with 325 microsatellite markers that had an average spacing of 11 cM and a mean heterozygosity of ∼75% covering all 22 autosomes. Genotype data were obtained from 562 individuals from 178 families from the Breda Study Cohort. These families were determined to have at least two members with type 2 diabetes. As a measure of obesity, the BMI of each diabetes patient was determined. The genotypes were analyzed using variance components (VCs) analysis implemented in GENEHUNTER 2 to determine quantitative trait loci influencing BMI. The VC analysis revealed two genomic regions showing VC logarithm of odds (LOD) scores ≥1.0 on chromosome 1 and chromosome 11. The regions of interest on both chromosomes were further investigated by fine‐mapping with additional markers, resulting in a VC LOD score of 1.5 on chromosome 1q and a VC LOD of 2.4 on chromosome 11q. The locus on chromosome 1 has been implicated previously in diabetes. The locus on chromosome 11 has been implicated previously in diabetes and obesity. 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subjects | Aged Analysis of Variance Body Mass Index Chromosomes, Human, Pair 1 Chromosomes, Human, Pair 11 Diabetes Mellitus - genetics Diabetes Mellitus, Type 2 - genetics Female genetics genome‐wide screening Genotype Heterozygote Humans Lod Score Male Microsatellite Repeats Middle Aged Obesity Quantitative Trait Loci type 2 diabetes |
title | Variance-Component Analysis of Obesity in Type 2 Diabetes Confirms Loci on Chromosomes 1q and 11q |
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