Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts
Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n
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| Veröffentlicht in: | American journal of human genetics 2023-06, Vol.110 (6), p.1008-1014 |
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| container_title | American journal of human genetics |
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| creator | Colbert, Sarah M.C. Wendt, Frank R. Pathak, Gita A. Helmer, Drew A. Hauser, Elizabeth R. Keller, Matthew C. Polimanti, Renato Johnson, Emma C. |
| description | Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n |
| doi_str_mv | 10.1016/j.ajhg.2023.04.007 |
| format | Article |
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This study found that genome-wide autozygosity is decreasing over generational time in three large cohorts of diverse genetic ancestries, though the rate of this decline varies by country and ancestry. This trend is most likely attributable to increases in urbanization and panmixia.</description><identifier>ISSN: 0002-9297</identifier><identifier>ISSN: 1537-6605</identifier><identifier>EISSN: 1537-6605</identifier><identifier>DOI: 10.1016/j.ajhg.2023.04.007</identifier><identifier>PMID: 37178685</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>autozygosity ; FROH ; Homozygote ; Humans ; panmixia ; Polymorphism, Single Nucleotide ; Population Health ; runs of homozygosity</subject><ispartof>American journal of human genetics, 2023-06, Vol.110 (6), p.1008-1014</ispartof><rights>2023 American Society of Human Genetics</rights><rights>Copyright © 2023 American Society of Human Genetics. Published by Elsevier Inc. All rights reserved.</rights><rights>2023 American Society of Human Genetics. 2023 American Society of Human Genetics</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-3318f0b686f123d62a5e6ba3e24db0de72cc1d2d90265d19019525ad000a1dd3</citedby><cites>FETCH-LOGICAL-c456t-3318f0b686f123d62a5e6ba3e24db0de72cc1d2d90265d19019525ad000a1dd3</cites><orcidid>0000-0003-3060-7471</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC10257001/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ajhg.2023.04.007$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,3550,27924,27925,45995,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/37178685$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Colbert, Sarah M.C.</creatorcontrib><creatorcontrib>Wendt, Frank R.</creatorcontrib><creatorcontrib>Pathak, Gita A.</creatorcontrib><creatorcontrib>Helmer, Drew A.</creatorcontrib><creatorcontrib>Hauser, Elizabeth R.</creatorcontrib><creatorcontrib>Keller, Matthew C.</creatorcontrib><creatorcontrib>Polimanti, Renato</creatorcontrib><creatorcontrib>Johnson, Emma C.</creatorcontrib><title>Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts</title><title>American journal of human genetics</title><addtitle>Am J Hum Genet</addtitle><description>Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, two from the US (All of Us, n = 82,474; the Million Veteran Program, n = 622,497) and one from the UK (UK Biobank, n = 380,899). Our results from a mixed-effect meta-analysis demonstrate an overall trend of decreasing autozygosity over generational time (meta-analyzed slope = −0.029, SE = 0.009, p = 6.03e−4). On the basis of our estimates, we would predict FROH to decline 0.29% for every 20-year increase in birth year. We determined that a model including an ancestry-by-country interaction term fit the data best, indicating that ancestry differences in this trend differ by country. We found further evidence to suggest a difference between the US and UK cohorts by meta-analyzing within country, observing a significant negative estimate in the US cohorts (meta-analyzed slope = −0.058, SE = 0.015, p = 1.50e−4) but a non-significant estimate in the UK (meta-analyzed slope = −0.001, SE = 0.008, p = 0.945). The association between autozygosity and birth year was substantially attenuated when accounting for educational attainment and income (meta-analyzed slope = −0.011, SE = 0.008, p = 0.167), suggesting they may partially account for decreasing autozygosity over time. Overall, we demonstrate decreasing autozygosity over time in a large, modern sample and speculate that this trend can be attributed to increases in urbanization and panmixia and differences in sociodemographic processes lead to country-specific differences in the rate of decline.
This study found that genome-wide autozygosity is decreasing over generational time in three large cohorts of diverse genetic ancestries, though the rate of this decline varies by country and ancestry. This trend is most likely attributable to increases in urbanization and panmixia.</description><subject>autozygosity</subject><subject>FROH</subject><subject>Homozygote</subject><subject>Humans</subject><subject>panmixia</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Population Health</subject><subject>runs of homozygosity</subject><issn>0002-9297</issn><issn>1537-6605</issn><issn>1537-6605</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2023</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU1v1DAQhi0EotvCH-CAfOSSMLbXToKQUFXKh1SJS--W157sepXEi-2suvx6vEqp4MLJ0swzr-15CHnDoGbA1Pt9bfa7bc2BixrWNUDzjKyYFE2lFMjnZAUAvOp411yQy5T2AIy1IF6SC9GwplWtXBH_Ge3gJz9tqZlz-HXahuTziYYjRpr9iB_o9UTx4TCEaLIPE_XT0mR09MOwVJw_ejebIdE-hpHmXUSkpYgxIbVhF2JOr8iLvhD4-vG8Ivdfbu9vvlV3P75-v7m-q-xaqlwJwdoeNqpVPePCKW4kqo0RyNduAw4bbi1z3HXAlXSsA9ZJLo0rfzXMOXFFPi2xh3kzorM45WgGfYh-NPGkg_H6387kd3objpoBl01ZUUl495gQw88ZU9ajTxaHwUwY5qR5y4RUjHeyoHxBbQwpReyf7mGgz470Xp8d6bMjDWtdHJWht3-_8Gnkj5QCfFwALGs6eow6WY-TRecj2qxd8P_L_w2nBqVC</recordid><startdate>20230601</startdate><enddate>20230601</enddate><creator>Colbert, Sarah M.C.</creator><creator>Wendt, Frank R.</creator><creator>Pathak, Gita A.</creator><creator>Helmer, Drew A.</creator><creator>Hauser, Elizabeth R.</creator><creator>Keller, Matthew C.</creator><creator>Polimanti, Renato</creator><creator>Johnson, Emma C.</creator><general>Elsevier Inc</general><general>Elsevier</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><scope>5PM</scope><orcidid>https://orcid.org/0000-0003-3060-7471</orcidid></search><sort><creationdate>20230601</creationdate><title>Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts</title><author>Colbert, Sarah M.C. ; Wendt, Frank R. ; Pathak, Gita A. ; Helmer, Drew A. ; Hauser, Elizabeth R. ; Keller, Matthew C. ; Polimanti, Renato ; Johnson, Emma C.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c456t-3318f0b686f123d62a5e6ba3e24db0de72cc1d2d90265d19019525ad000a1dd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2023</creationdate><topic>autozygosity</topic><topic>FROH</topic><topic>Homozygote</topic><topic>Humans</topic><topic>panmixia</topic><topic>Polymorphism, Single Nucleotide</topic><topic>Population Health</topic><topic>runs of homozygosity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Colbert, Sarah M.C.</creatorcontrib><creatorcontrib>Wendt, Frank R.</creatorcontrib><creatorcontrib>Pathak, Gita A.</creatorcontrib><creatorcontrib>Helmer, Drew A.</creatorcontrib><creatorcontrib>Hauser, Elizabeth R.</creatorcontrib><creatorcontrib>Keller, Matthew C.</creatorcontrib><creatorcontrib>Polimanti, Renato</creatorcontrib><creatorcontrib>Johnson, Emma C.</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><collection>PubMed Central (Full Participant titles)</collection><jtitle>American journal of human genetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Colbert, Sarah M.C.</au><au>Wendt, Frank R.</au><au>Pathak, Gita A.</au><au>Helmer, Drew A.</au><au>Hauser, Elizabeth R.</au><au>Keller, Matthew C.</au><au>Polimanti, Renato</au><au>Johnson, Emma C.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts</atitle><jtitle>American journal of human genetics</jtitle><addtitle>Am J Hum Genet</addtitle><date>2023-06-01</date><risdate>2023</risdate><volume>110</volume><issue>6</issue><spage>1008</spage><epage>1014</epage><pages>1008-1014</pages><issn>0002-9297</issn><issn>1537-6605</issn><eissn>1537-6605</eissn><abstract>Previous studies have hypothesized that autozygosity is decreasing over generational time. However, these studies were limited to relatively small samples (n < 11,000) lacking in diversity, which may limit the generalizability of their findings. We present data that partially support this hypothesis from three large cohorts of diverse ancestries, two from the US (All of Us, n = 82,474; the Million Veteran Program, n = 622,497) and one from the UK (UK Biobank, n = 380,899). Our results from a mixed-effect meta-analysis demonstrate an overall trend of decreasing autozygosity over generational time (meta-analyzed slope = −0.029, SE = 0.009, p = 6.03e−4). On the basis of our estimates, we would predict FROH to decline 0.29% for every 20-year increase in birth year. We determined that a model including an ancestry-by-country interaction term fit the data best, indicating that ancestry differences in this trend differ by country. We found further evidence to suggest a difference between the US and UK cohorts by meta-analyzing within country, observing a significant negative estimate in the US cohorts (meta-analyzed slope = −0.058, SE = 0.015, p = 1.50e−4) but a non-significant estimate in the UK (meta-analyzed slope = −0.001, SE = 0.008, p = 0.945). The association between autozygosity and birth year was substantially attenuated when accounting for educational attainment and income (meta-analyzed slope = −0.011, SE = 0.008, p = 0.167), suggesting they may partially account for decreasing autozygosity over time. Overall, we demonstrate decreasing autozygosity over time in a large, modern sample and speculate that this trend can be attributed to increases in urbanization and panmixia and differences in sociodemographic processes lead to country-specific differences in the rate of decline.
This study found that genome-wide autozygosity is decreasing over generational time in three large cohorts of diverse genetic ancestries, though the rate of this decline varies by country and ancestry. This trend is most likely attributable to increases in urbanization and panmixia.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>37178685</pmid><doi>10.1016/j.ajhg.2023.04.007</doi><tpages>7</tpages><orcidid>https://orcid.org/0000-0003-3060-7471</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Open Access: PubMed Central; MEDLINE; Elsevier ScienceDirect Journals Complete; Cell Press Free Archives(OpenAccess); Free E-Journal (出版社公開部分のみ） |
| subjects | autozygosity FROH Homozygote Humans panmixia Polymorphism, Single Nucleotide Population Health runs of homozygosity |
| title | Declining autozygosity over time: An exploration in over 1 million individuals from three diverse cohorts |
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