Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity
•This comprehensive review seeks to determine the genetic variants associated with exceptional longevity.•Meta-analyses of nine genetic polymorphisms previously associated with exceptional longevity (aged 85+) were undertaken.•ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795...
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| Veröffentlicht in: | Mechanisms of ageing and development 2018-10, Vol.175, p.24-34 |
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| creator | Revelas, Mary Thalamuthu, Anbupalam Oldmeadow, Christopher Evans, Tiffany-Jane Armstrong, Nicola J. Kwok, John B. Brodaty, Henry Schofield, Peter R. Scott, Rodney J. Sachdev, Perminder S. Attia, John R. Mather, Karen A. |
| description | •This comprehensive review seeks to determine the genetic variants associated with exceptional longevity.•Meta-analyses of nine genetic polymorphisms previously associated with exceptional longevity (aged 85+) were undertaken.•ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity.•The significant pooled effect sizes (odds ratios) ranged from 0.42 (APOE ε4) to 1.45 (FOXO3A males).•The significant modest effect sizes observed suggest many genes of small influence play a role in exceptional longevity.
Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses.
Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts.
Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males).
In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls. |
| doi_str_mv | 10.1016/j.mad.2018.06.002 |
| format | Article |
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Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses.
Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts.
Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males).
In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls.</description><identifier>ISSN: 0047-6374</identifier><identifier>EISSN: 1872-6216</identifier><identifier>DOI: 10.1016/j.mad.2018.06.002</identifier><identifier>PMID: 29890178</identifier><language>eng</language><publisher>Ireland: Elsevier B.V</publisher><subject>ACE ; Age Factors ; Aged, 80 and over ; APOE ; Centenarians ; Female ; FOXO3A ; Genotype ; Healthy Aging - genetics ; Heredity ; Humans ; Longevity ; Longevity - genetics ; Male ; Meta-analysis ; Pedigree ; Phenotype ; Polymorphism, Genetic</subject><ispartof>Mechanisms of ageing and development, 2018-10, Vol.175, p.24-34</ispartof><rights>2018 Elsevier B.V.</rights><rights>Copyright © 2018 Elsevier B.V. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-ba7014ce07b02ec3c243bd14a4687cd8b4eed60e6c290d44231a4d3ae16c49b23</citedby><cites>FETCH-LOGICAL-c353t-ba7014ce07b02ec3c243bd14a4687cd8b4eed60e6c290d44231a4d3ae16c49b23</cites><orcidid>0000-0001-9800-1308 ; 0000-0002-9595-3220</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.mad.2018.06.002$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29890178$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Revelas, Mary</creatorcontrib><creatorcontrib>Thalamuthu, Anbupalam</creatorcontrib><creatorcontrib>Oldmeadow, Christopher</creatorcontrib><creatorcontrib>Evans, Tiffany-Jane</creatorcontrib><creatorcontrib>Armstrong, Nicola J.</creatorcontrib><creatorcontrib>Kwok, John B.</creatorcontrib><creatorcontrib>Brodaty, Henry</creatorcontrib><creatorcontrib>Schofield, Peter R.</creatorcontrib><creatorcontrib>Scott, Rodney J.</creatorcontrib><creatorcontrib>Sachdev, Perminder S.</creatorcontrib><creatorcontrib>Attia, John R.</creatorcontrib><creatorcontrib>Mather, Karen A.</creatorcontrib><title>Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity</title><title>Mechanisms of ageing and development</title><addtitle>Mech Ageing Dev</addtitle><description>•This comprehensive review seeks to determine the genetic variants associated with exceptional longevity.•Meta-analyses of nine genetic polymorphisms previously associated with exceptional longevity (aged 85+) were undertaken.•ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity.•The significant pooled effect sizes (odds ratios) ranged from 0.42 (APOE ε4) to 1.45 (FOXO3A males).•The significant modest effect sizes observed suggest many genes of small influence play a role in exceptional longevity.
Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses.
Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts.
Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males).
In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls.</description><subject>ACE</subject><subject>Age Factors</subject><subject>Aged, 80 and over</subject><subject>APOE</subject><subject>Centenarians</subject><subject>Female</subject><subject>FOXO3A</subject><subject>Genotype</subject><subject>Healthy Aging - genetics</subject><subject>Heredity</subject><subject>Humans</subject><subject>Longevity</subject><subject>Longevity - genetics</subject><subject>Male</subject><subject>Meta-analysis</subject><subject>Pedigree</subject><subject>Phenotype</subject><subject>Polymorphism, Genetic</subject><issn>0047-6374</issn><issn>1872-6216</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kM1KxDAURoMoOo4-gBvJ0k3rTZpJW1yJ-AeCILqUkCZ3ZjK0TW0y6ry9kVGXrrI53-HmEHLCIGfA5Pkq77TNObAqB5kD8B0yYVXJM8mZ3CUTAFFmsijFATkMYQUATHC5Tw54XdXAympCXp_w3eEH1b2lHUad6V63m-AC9XO6wB6jM3Tw7abz47B0oQtUh-CN0xEt_XBxSfHT4BCdT0O6XHe6p63vF0kbN0dkb67bgMc_75S83Fw_X91lD4-391eXD5kpZkXMGl2mywxC2QBHUxguisYyoYWsSmOrRiBaCSgNr8EKwQumhS00MmlE3fBiSs623mH0b2sMUXUuGGxb3aNfB8VhJmo-q0tIKNuiZvQhjDhXw-g6PW4UA_VdVa1Uqqq-qyqQKlVNm9Mf_brp0P4tfjMm4GILYPpk6jmqYBz2Bq0b0URlvftH_wU1FYmG</recordid><startdate>201810</startdate><enddate>201810</enddate><creator>Revelas, Mary</creator><creator>Thalamuthu, Anbupalam</creator><creator>Oldmeadow, Christopher</creator><creator>Evans, Tiffany-Jane</creator><creator>Armstrong, Nicola J.</creator><creator>Kwok, John B.</creator><creator>Brodaty, Henry</creator><creator>Schofield, Peter R.</creator><creator>Scott, Rodney J.</creator><creator>Sachdev, Perminder S.</creator><creator>Attia, John R.</creator><creator>Mather, Karen A.</creator><general>Elsevier B.V</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>7X8</scope><orcidid>https://orcid.org/0000-0001-9800-1308</orcidid><orcidid>https://orcid.org/0000-0002-9595-3220</orcidid></search><sort><creationdate>201810</creationdate><title>Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity</title><author>Revelas, Mary ; Thalamuthu, Anbupalam ; Oldmeadow, Christopher ; Evans, Tiffany-Jane ; Armstrong, Nicola J. ; Kwok, John B. ; Brodaty, Henry ; Schofield, Peter R. ; Scott, Rodney J. ; Sachdev, Perminder S. ; Attia, John R. ; Mather, Karen A.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-ba7014ce07b02ec3c243bd14a4687cd8b4eed60e6c290d44231a4d3ae16c49b23</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>ACE</topic><topic>Age Factors</topic><topic>Aged, 80 and over</topic><topic>APOE</topic><topic>Centenarians</topic><topic>Female</topic><topic>FOXO3A</topic><topic>Genotype</topic><topic>Healthy Aging - genetics</topic><topic>Heredity</topic><topic>Humans</topic><topic>Longevity</topic><topic>Longevity - genetics</topic><topic>Male</topic><topic>Meta-analysis</topic><topic>Pedigree</topic><topic>Phenotype</topic><topic>Polymorphism, Genetic</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Revelas, Mary</creatorcontrib><creatorcontrib>Thalamuthu, Anbupalam</creatorcontrib><creatorcontrib>Oldmeadow, Christopher</creatorcontrib><creatorcontrib>Evans, Tiffany-Jane</creatorcontrib><creatorcontrib>Armstrong, Nicola J.</creatorcontrib><creatorcontrib>Kwok, John B.</creatorcontrib><creatorcontrib>Brodaty, Henry</creatorcontrib><creatorcontrib>Schofield, Peter R.</creatorcontrib><creatorcontrib>Scott, Rodney J.</creatorcontrib><creatorcontrib>Sachdev, Perminder S.</creatorcontrib><creatorcontrib>Attia, John R.</creatorcontrib><creatorcontrib>Mather, Karen A.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Mechanisms of ageing and development</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Revelas, Mary</au><au>Thalamuthu, Anbupalam</au><au>Oldmeadow, Christopher</au><au>Evans, Tiffany-Jane</au><au>Armstrong, Nicola J.</au><au>Kwok, John B.</au><au>Brodaty, Henry</au><au>Schofield, Peter R.</au><au>Scott, Rodney J.</au><au>Sachdev, Perminder S.</au><au>Attia, John R.</au><au>Mather, Karen A.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity</atitle><jtitle>Mechanisms of ageing and development</jtitle><addtitle>Mech Ageing Dev</addtitle><date>2018-10</date><risdate>2018</risdate><volume>175</volume><spage>24</spage><epage>34</epage><pages>24-34</pages><issn>0047-6374</issn><eissn>1872-6216</eissn><abstract>•This comprehensive review seeks to determine the genetic variants associated with exceptional longevity.•Meta-analyses of nine genetic polymorphisms previously associated with exceptional longevity (aged 85+) were undertaken.•ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity.•The significant pooled effect sizes (odds ratios) ranged from 0.42 (APOE ε4) to 1.45 (FOXO3A males).•The significant modest effect sizes observed suggest many genes of small influence play a role in exceptional longevity.
Many factors contribute to exceptional longevity, with genetics playing a significant role. However, to date, genetic studies examining exceptional longevity have been inconclusive. This comprehensive review seeks to determine the genetic variants associated with exceptional longevity by undertaking meta-analyses.
Meta-analyses of genetic polymorphisms previously associated with exceptional longevity (85+) were undertaken. For each variant, meta-analyses were performed if there were data from at least three independent studies available, including two unpublished additional cohorts.
Five polymorphisms, ACE rs4340, APOE ε2/3/4, FOXO3A rs2802292, KLOTHO KL-VS and IL6 rs1800795 were significantly associated with exceptional longevity, with the pooled effect sizes (odds ratios) ranging from 0.42 (APOE ε4) to 1.45 (FOXO3A males).
In general, the observed modest effect sizes of the significant variants suggest many genes of small influence play a role in exceptional longevity, which is consistent with results for other polygenic traits. Our results also suggest that genes related to cardiovascular health may be implicated in exceptional longevity. Future studies should examine the roles of gender and ethnicity and carefully consider study design, including the selection of appropriate controls.</abstract><cop>Ireland</cop><pub>Elsevier B.V</pub><pmid>29890178</pmid><doi>10.1016/j.mad.2018.06.002</doi><tpages>11</tpages><orcidid>https://orcid.org/0000-0001-9800-1308</orcidid><orcidid>https://orcid.org/0000-0002-9595-3220</orcidid></addata></record> |
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| subjects | ACE Age Factors Aged, 80 and over APOE Centenarians Female FOXO3A Genotype Healthy Aging - genetics Heredity Humans Longevity Longevity - genetics Male Meta-analysis Pedigree Phenotype Polymorphism, Genetic |
| title | Review and meta-analysis of genetic polymorphisms associated with exceptional human longevity |
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