A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci
Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success. We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of bo...
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| creator | Kerber, Richard A O'Brien, Elizabeth Boucher, Kenneth M Smith, Ken R Cawthon, Richard M |
| description | Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success.
We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related "affected individuals", defined as those in the top quartile for both excess longevity (EL = observed lifespan - expected lifespan) and familial excess longevity (FEL = weighted average EL across all relatives). A whole-genome scan for genetic linkage was performed on this sample using a panel of 1100 microsatellite markers. A strongly suggestive peak (Z = 4.2, Monte Carlo-adjusted p-value 0.09) was observed in the vicinity of D3S3547 on chromosome 3p24.1, at a point nearly identical to that reported recently by an independent team of researchers from Harvard Medical School (HMS). Meta-analysis of linkage scores on 3p from the two studies produced a minimum nominal p-value of 1.005×10(-9) at 55 cM. Other potentially noteworthy peaks in our data occur on 18q23-24, 8q23, and 17q21. Meta-analysis results from combined UPDB and HMS data yielded additional support, but not formal replication, for linkage on 8q, 9q, and 17q.
Corroboration of the linkage of exceptional longevity to 3p22-24 greatly strengthens the case that genes in this region affect variation in longevity and suggest, therefore, an important role in the regulation of human lifespan. Future efforts should include intensive study of the 3p22-24 region. |
| doi_str_mv | 10.1371/journal.pone.0034746 |
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We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related "affected individuals", defined as those in the top quartile for both excess longevity (EL = observed lifespan - expected lifespan) and familial excess longevity (FEL = weighted average EL across all relatives). A whole-genome scan for genetic linkage was performed on this sample using a panel of 1100 microsatellite markers. A strongly suggestive peak (Z = 4.2, Monte Carlo-adjusted p-value 0.09) was observed in the vicinity of D3S3547 on chromosome 3p24.1, at a point nearly identical to that reported recently by an independent team of researchers from Harvard Medical School (HMS). Meta-analysis of linkage scores on 3p from the two studies produced a minimum nominal p-value of 1.005×10(-9) at 55 cM. Other potentially noteworthy peaks in our data occur on 18q23-24, 8q23, and 17q21. Meta-analysis results from combined UPDB and HMS data yielded additional support, but not formal replication, for linkage on 8q, 9q, and 17q.
Corroboration of the linkage of exceptional longevity to 3p22-24 greatly strengthens the case that genes in this region affect variation in longevity and suggest, therefore, an important role in the regulation of human lifespan. Future efforts should include intensive study of the 3p22-24 region.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0034746</identifier><identifier>PMID: 22506048</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Age ; Aged, 80 and over ; Aging ; Analysis ; Biology ; Cancer ; Chromosome 3 ; Chromosomes, Human, Pair 3 ; Cytokines ; Epidemiology ; Female ; Free electron lasers ; Free radicals ; Gene expression ; Genetic aspects ; Genetic Linkage ; Genetic Loci ; Genetic markers ; Genetic Variation ; Genetics ; Genome-Wide Association Study - methods ; Genomes ; Genomics ; Growth factors ; Humans ; Life span ; Linkage analysis ; Loci ; Longevity ; Longevity - genetics ; Male ; Medical research ; Medicine ; Meta-analysis ; Microsatellites ; Mortality ; Population ; Social and Behavioral Sciences ; Studies ; Utah</subject><ispartof>PloS one, 2012-04, Vol.7 (4), p.e34746-e34746</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>2012 Kerber et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Kerber et al. 2012</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-cc42e07569a86d5d7277e7ffb2852fffadcbfadca13fbad881a8500eb420f403</citedby><cites>FETCH-LOGICAL-c692t-cc42e07569a86d5d7277e7ffb2852fffadcbfadca13fbad881a8500eb420f403</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323558/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3323558/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,315,729,782,786,866,887,2104,2930,23873,27931,27932,53798,53800</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22506048$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><contributor>Toland, Amanda Ewart</contributor><creatorcontrib>Kerber, Richard A</creatorcontrib><creatorcontrib>O'Brien, Elizabeth</creatorcontrib><creatorcontrib>Boucher, Kenneth M</creatorcontrib><creatorcontrib>Smith, Ken R</creatorcontrib><creatorcontrib>Cawthon, Richard M</creatorcontrib><title>A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success.
We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related "affected individuals", defined as those in the top quartile for both excess longevity (EL = observed lifespan - expected lifespan) and familial excess longevity (FEL = weighted average EL across all relatives). A whole-genome scan for genetic linkage was performed on this sample using a panel of 1100 microsatellite markers. A strongly suggestive peak (Z = 4.2, Monte Carlo-adjusted p-value 0.09) was observed in the vicinity of D3S3547 on chromosome 3p24.1, at a point nearly identical to that reported recently by an independent team of researchers from Harvard Medical School (HMS). Meta-analysis of linkage scores on 3p from the two studies produced a minimum nominal p-value of 1.005×10(-9) at 55 cM. Other potentially noteworthy peaks in our data occur on 18q23-24, 8q23, and 17q21. Meta-analysis results from combined UPDB and HMS data yielded additional support, but not formal replication, for linkage on 8q, 9q, and 17q.
Corroboration of the linkage of exceptional longevity to 3p22-24 greatly strengthens the case that genes in this region affect variation in longevity and suggest, therefore, an important role in the regulation of human lifespan. Future efforts should include intensive study of the 3p22-24 region.</description><subject>Age</subject><subject>Aged, 80 and over</subject><subject>Aging</subject><subject>Analysis</subject><subject>Biology</subject><subject>Cancer</subject><subject>Chromosome 3</subject><subject>Chromosomes, Human, Pair 3</subject><subject>Cytokines</subject><subject>Epidemiology</subject><subject>Female</subject><subject>Free electron lasers</subject><subject>Free radicals</subject><subject>Gene expression</subject><subject>Genetic aspects</subject><subject>Genetic Linkage</subject><subject>Genetic Loci</subject><subject>Genetic markers</subject><subject>Genetic Variation</subject><subject>Genetics</subject><subject>Genome-Wide Association Study - methods</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Growth factors</subject><subject>Humans</subject><subject>Life span</subject><subject>Linkage analysis</subject><subject>Loci</subject><subject>Longevity</subject><subject>Longevity - genetics</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Meta-analysis</subject><subject>Microsatellites</subject><subject>Mortality</subject><subject>Population</subject><subject>Social and Behavioral Sciences</subject><subject>Studies</subject><subject>Utah</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk11rFDEUhgdRbK3-A9GAIHoxaybJzGRvhFL8WCgUtHgbziYns1kzk3UyU7v_3qy7LTvSCwkkIXneN8nJOVn2sqCzgtfFh3UY-w78bBM6nFHKRS2qR9lpMecsrxjlj4_mJ9mzGNeUllxW1dPshLGSVlTI0-z2nDTYhRbz384gicNotqTHjXcaBozEu-4nNEiCJXzDWM4EGQLB26HHFokPXYM3btgS15HV2EIXCXSGJKtucNYlg02I0S09EjDGDS6kKyeZds-zJxZ8xBeH8Sy7_vzp-uJrfnn1ZXFxfpnras6GXGvBkNZlNQdZmdLUrK6xtnbJZMmstWD0ctdBwe0SjJQFyJJSXApGraD8LHu9t934ENUhZlEVnAkhZCV5IhZ7wgRYq03vWui3KoBTfxdC3yjoB6c9Kg2VLmpKjZZJbhkY1HMGUElgaAqWvD4eThuXLRqdotCDn5hOdzq3Uk24UZwzXpYyGbw7GPTh14hxUK2LGr2HDsOY7k1pMS8l43VC3_yDPvy6A9VAeoDrbEjn6p2pOhd1XXAuyjJRsweo1Ay2TqcEsy6tTwTvJ4LEDCkpGhhjVIvv3_6fvfoxZd8esSsEP6xi8OMuceIUFHtQ9ynBerT3QS6o2tXHXTTUrj7UoT6S7NXxB92L7gqC_wFo5QxN</recordid><startdate>20120410</startdate><enddate>20120410</enddate><creator>Kerber, Richard A</creator><creator>O'Brien, Elizabeth</creator><creator>Boucher, Kenneth M</creator><creator>Smith, Ken R</creator><creator>Cawthon, Richard M</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</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>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120410</creationdate><title>A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci</title><author>Kerber, Richard A ; O'Brien, Elizabeth ; Boucher, Kenneth M ; Smith, Ken R ; Cawthon, Richard M</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-cc42e07569a86d5d7277e7ffb2852fffadcbfadca13fbad881a8500eb420f403</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Age</topic><topic>Aged, 80 and over</topic><topic>Aging</topic><topic>Analysis</topic><topic>Biology</topic><topic>Cancer</topic><topic>Chromosome 3</topic><topic>Chromosomes, Human, Pair 3</topic><topic>Cytokines</topic><topic>Epidemiology</topic><topic>Female</topic><topic>Free electron lasers</topic><topic>Free radicals</topic><topic>Gene expression</topic><topic>Genetic aspects</topic><topic>Genetic Linkage</topic><topic>Genetic Loci</topic><topic>Genetic markers</topic><topic>Genetic Variation</topic><topic>Genetics</topic><topic>Genome-Wide Association Study - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><collection>DOAJ Directory of Open Access Journals</collection><jtitle>PloS one</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kerber, Richard A</au><au>O'Brien, Elizabeth</au><au>Boucher, Kenneth M</au><au>Smith, Ken R</au><au>Cawthon, Richard M</au><au>Toland, Amanda Ewart</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2012-04-10</date><risdate>2012</risdate><volume>7</volume><issue>4</issue><spage>e34746</spage><epage>e34746</epage><pages>e34746-e34746</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>Although there is abundant evidence that human longevity is heritable, efforts to map loci responsible for variation in human lifespan have had limited success.
We identified individuals from a large multigenerational population database (the Utah Population Database) who exhibited high levels of both familial longevity and individual longevity. This selection identified 325 related "affected individuals", defined as those in the top quartile for both excess longevity (EL = observed lifespan - expected lifespan) and familial excess longevity (FEL = weighted average EL across all relatives). A whole-genome scan for genetic linkage was performed on this sample using a panel of 1100 microsatellite markers. A strongly suggestive peak (Z = 4.2, Monte Carlo-adjusted p-value 0.09) was observed in the vicinity of D3S3547 on chromosome 3p24.1, at a point nearly identical to that reported recently by an independent team of researchers from Harvard Medical School (HMS). Meta-analysis of linkage scores on 3p from the two studies produced a minimum nominal p-value of 1.005×10(-9) at 55 cM. Other potentially noteworthy peaks in our data occur on 18q23-24, 8q23, and 17q21. Meta-analysis results from combined UPDB and HMS data yielded additional support, but not formal replication, for linkage on 8q, 9q, and 17q.
Corroboration of the linkage of exceptional longevity to 3p22-24 greatly strengthens the case that genes in this region affect variation in longevity and suggest, therefore, an important role in the regulation of human lifespan. Future efforts should include intensive study of the 3p22-24 region.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22506048</pmid><doi>10.1371/journal.pone.0034746</doi><tpages>e34746</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; DOAJ Directory of Open Access Journals; Public Library of Science (PLoS) Journals Open Access; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Age Aged, 80 and over Aging Analysis Biology Cancer Chromosome 3 Chromosomes, Human, Pair 3 Cytokines Epidemiology Female Free electron lasers Free radicals Gene expression Genetic aspects Genetic Linkage Genetic Loci Genetic markers Genetic Variation Genetics Genome-Wide Association Study - methods Genomes Genomics Growth factors Humans Life span Linkage analysis Loci Longevity Longevity - genetics Male Medical research Medicine Meta-analysis Microsatellites Mortality Population Social and Behavioral Sciences Studies Utah |
| title | A genome-wide study replicates linkage of 3p22-24 to extreme longevity in humans and identifies possible additional loci |
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