Human Cardiovascular Disease IBC Chip-Wide Association with Weight Loss and Weight Regain in the Look AHEAD Trial
Background/Aims: The present study identified genetic predictors of weight change during behavioral weight loss treatment. Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle...
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| Veröffentlicht in: | Human heredity 2013-01, Vol.75 (2/4), p.160-174 |
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| creator | McCaffery, Jeanne M. Papandonatos, George D. Huggins, Gordon S. Peter, Inga Erar, Bahar Kahn, Steven E. Knowler, William C. Lipkin, Edward W. Kitabchi, Abbas E. Wagenknecht, Lynne E. Wing, Rena R. |
| description | Background/Aims: The present study identified genetic predictors of weight change during behavioral weight loss treatment. Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost ≥3% at year 1. Results: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. Conclusions: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment. |
| doi_str_mv | 10.1159/000353181 |
| format | Article |
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Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost ≥3% at year 1. Results: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. Conclusions: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment.</description><identifier>ISSN: 0001-5652</identifier><identifier>ISSN: 1423-0062</identifier><identifier>ISBN: 3318024775</identifier><identifier>ISBN: 9783318024777</identifier><identifier>EISSN: 1423-0062</identifier><identifier>EISBN: 3318024783</identifier><identifier>EISBN: 9783318024784</identifier><identifier>DOI: 10.1159/000353181</identifier><identifier>PMID: 24081232</identifier><language>eng</language><publisher>Basel, Switzerland: S. Karger AG</publisher><subject>Adipose tissue ; Aged ; ATP Binding Cassette Transporter, Subfamily B, Member 11 ; ATP-Binding Cassette Transporters - genetics ; Cardiovascular disease ; Cardiovascular Diseases - genetics ; Cohort Studies ; Female ; Further Section ; Genetics ; Genome-Wide Association Study ; Humans ; Male ; Middle Aged ; Obesity ; Oligonucleotide Array Sequence Analysis ; Polymorphism, Single Nucleotide - genetics ; Receptor Activator of Nuclear Factor-kappa B - genetics ; Weight control ; Weight Gain - genetics ; Weight Loss - genetics</subject><ispartof>Human heredity, 2013-01, Vol.75 (2/4), p.160-174</ispartof><rights>2013 S. Karger AG</rights><rights>2013 S. Karger AG, Basel</rights><rights>2013 S. Karger AG, Basel.</rights><rights>Copyright (c) 2013 S. Karger AG, Basel</rights><rights>2013 S. Karger AG, Basel 2013</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c507t-a82c86b95fd8bd26c5cb78cd56a71d7f0fe495c40c190f5191fa23ae6376ca6a3</citedby><cites>FETCH-LOGICAL-c507t-a82c86b95fd8bd26c5cb78cd56a71d7f0fe495c40c190f5191fa23ae6376ca6a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/48513531$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/48513531$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,777,781,800,882,2423,27905,27906,57998,58231</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24081232$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>McCaffery, Jeanne M.</creatorcontrib><creatorcontrib>Papandonatos, George D.</creatorcontrib><creatorcontrib>Huggins, Gordon S.</creatorcontrib><creatorcontrib>Peter, Inga</creatorcontrib><creatorcontrib>Erar, Bahar</creatorcontrib><creatorcontrib>Kahn, Steven E.</creatorcontrib><creatorcontrib>Knowler, William C.</creatorcontrib><creatorcontrib>Lipkin, Edward W.</creatorcontrib><creatorcontrib>Kitabchi, Abbas E.</creatorcontrib><creatorcontrib>Wagenknecht, Lynne E.</creatorcontrib><creatorcontrib>Wing, Rena R.</creatorcontrib><creatorcontrib>The Look AHEAD Research Group</creatorcontrib><creatorcontrib>The Genetic Subgroup of Look AHEAD</creatorcontrib><creatorcontrib>Look AHEAD Research Group</creatorcontrib><creatorcontrib>Genetic Subgroup of Look AHEAD</creatorcontrib><creatorcontrib>The Genetic Subgroup of Look AHEAD and The Look AHEAD Research Group</creatorcontrib><title>Human Cardiovascular Disease IBC Chip-Wide Association with Weight Loss and Weight Regain in the Look AHEAD Trial</title><title>Human heredity</title><addtitle>Hum Hered</addtitle><description>Background/Aims: The present study identified genetic predictors of weight change during behavioral weight loss treatment. Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost ≥3% at year 1. Results: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. Conclusions: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment.</description><subject>Adipose tissue</subject><subject>Aged</subject><subject>ATP Binding Cassette Transporter, Subfamily B, Member 11</subject><subject>ATP-Binding Cassette Transporters - genetics</subject><subject>Cardiovascular disease</subject><subject>Cardiovascular Diseases - genetics</subject><subject>Cohort Studies</subject><subject>Female</subject><subject>Further Section</subject><subject>Genetics</subject><subject>Genome-Wide Association Study</subject><subject>Humans</subject><subject>Male</subject><subject>Middle Aged</subject><subject>Obesity</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Polymorphism, Single Nucleotide - genetics</subject><subject>Receptor Activator of Nuclear Factor-kappa B - genetics</subject><subject>Weight control</subject><subject>Weight Gain - genetics</subject><subject>Weight Loss - genetics</subject><issn>0001-5652</issn><issn>1423-0062</issn><issn>1423-0062</issn><isbn>3318024775</isbn><isbn>9783318024777</isbn><isbn>3318024783</isbn><isbn>9783318024784</isbn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2013</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>8G5</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>GUQSH</sourceid><sourceid>M2O</sourceid><recordid>eNqNkk1vEzEQhs2XaFo4cAdkiQscFvy59l6Q0jSwlSIhoaIeVxOvN-t0s07t3aL-e1ylTQBxQLI0Gr2P3_GMB6FXlHykVBafCCFccqrpI3TMUyRMKM0fowkVjGeE5OzJQVDyKZqkGzSTuWRH6DjGdUo1Ufw5OmKCaMo4m6DrctxAj2cQaudvIJqxg4DPXLQQLT4_neFZ67bZpastnsbojYPB-R7_dEOLL61btQNe-Bgx9PVD_t2uwPU4naG1SfVXeFrOp2f4IjjoXqBnDXTRvryPJ-jHl_nFrMwW376ez6aLzEiihgw0MzpfFrKp9bJmuZFmqbSpZQ6K1qohjRWFNIIYWpBG0oI2wDjYnKvcQA78BH3e-W7H5cbWxvZDgK7aBreBcFt5cNWfSu_aauVvKsGk0oImg_f3BsFfjzYO1cZFY7sOeuvHWFEhONdCpZH-F6q4onlC3_2Frv0Y-jSJROUk9c4pSdSHHWVCGm6wzf7dlFR321DttyGxb39vdE8-fPKh5BWElQ17oCznO4tqWzeJev1Pal_lzU5ex8EfVKElvSP4L5ibx7o</recordid><startdate>20130101</startdate><enddate>20130101</enddate><creator>McCaffery, Jeanne M.</creator><creator>Papandonatos, George D.</creator><creator>Huggins, Gordon S.</creator><creator>Peter, Inga</creator><creator>Erar, Bahar</creator><creator>Kahn, Steven E.</creator><creator>Knowler, William C.</creator><creator>Lipkin, Edward W.</creator><creator>Kitabchi, Abbas E.</creator><creator>Wagenknecht, Lynne E.</creator><creator>Wing, Rena R.</creator><general>S. 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Human heredity</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>McCaffery, Jeanne M.</au><au>Papandonatos, George D.</au><au>Huggins, Gordon S.</au><au>Peter, Inga</au><au>Erar, Bahar</au><au>Kahn, Steven E.</au><au>Knowler, William C.</au><au>Lipkin, Edward W.</au><au>Kitabchi, Abbas E.</au><au>Wagenknecht, Lynne E.</au><au>Wing, Rena R.</au><aucorp>The Look AHEAD Research Group</aucorp><aucorp>The Genetic Subgroup of Look AHEAD</aucorp><aucorp>Look AHEAD Research Group</aucorp><aucorp>Genetic Subgroup of Look AHEAD</aucorp><aucorp>The Genetic Subgroup of Look AHEAD and The Look AHEAD Research Group</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Human Cardiovascular Disease IBC Chip-Wide Association with Weight Loss and Weight Regain in the Look AHEAD Trial</atitle><jtitle>Human heredity</jtitle><addtitle>Hum Hered</addtitle><date>2013-01-01</date><risdate>2013</risdate><volume>75</volume><issue>2/4</issue><spage>160</spage><epage>174</epage><pages>160-174</pages><issn>0001-5652</issn><issn>1423-0062</issn><eissn>1423-0062</eissn><isbn>3318024775</isbn><isbn>9783318024777</isbn><eisbn>3318024783</eisbn><eisbn>9783318024784</eisbn><abstract>Background/Aims: The present study identified genetic predictors of weight change during behavioral weight loss treatment. Methods: Participants were 3,899 overweight/obese individuals with type 2 diabetes from Look AHEAD, a randomized controlled trial to determine the effects of intensive lifestyle intervention (ILI), including weight loss and physical activity, relative to diabetes support and education, on cardiovascular outcomes. Analyses focused on associations of single nucleotide polymorphisms (SNPs) on the Illumina CARe iSelect (IBC) chip (minor allele frequency >5%; n = 31,959) with weight change at year 1 and year 4, and weight regain at year 4, among individuals who lost ≥3% at year 1. Results: Two novel regions of significant chip-wide association with year-1 weight loss in ILI were identified (p < 2.96E-06). ABCB11 rs484066 was associated with 1.16 kg higher weight per minor allele at year 1, whereas TNFRSF11A, or RANK, rs17069904 was associated with 1.70 kg lower weight per allele at year 1. Conclusions: This study, the largest to date on genetic predictors of weight loss and regain, indicates that SNPs within ABCB11, related to bile salt transfer, and TNFRSF11A, implicated in adipose tissue physiology, predict the magnitude of weight loss during behavioral intervention. These results provide new insights into potential biological mechanisms and may ultimately inform weight loss treatment.</abstract><cop>Basel, Switzerland</cop><pub>S. Karger AG</pub><pmid>24081232</pmid><doi>10.1159/000353181</doi><tpages>15</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | Human heredity, 2013-01, Vol.75 (2/4), p.160-174 |
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| subjects | Adipose tissue Aged ATP Binding Cassette Transporter, Subfamily B, Member 11 ATP-Binding Cassette Transporters - genetics Cardiovascular disease Cardiovascular Diseases - genetics Cohort Studies Female Further Section Genetics Genome-Wide Association Study Humans Male Middle Aged Obesity Oligonucleotide Array Sequence Analysis Polymorphism, Single Nucleotide - genetics Receptor Activator of Nuclear Factor-kappa B - genetics Weight control Weight Gain - genetics Weight Loss - genetics |
| title | Human Cardiovascular Disease IBC Chip-Wide Association with Weight Loss and Weight Regain in the Look AHEAD Trial |
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