The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry
The genetic basis of amyotrophic lateral sclerosis (ALS) is not entirely clear. While there are families with rare highly penetrant mutations in Cu/Zn superoxide dismutase 1 and several other genes that cause apparent Mendelian inheritance of the disease, most ALS occurs in families without another...
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| Veröffentlicht in: | PloS one 2011-11, Vol.6 (11), p.e27985-e27985 |
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| description | The genetic basis of amyotrophic lateral sclerosis (ALS) is not entirely clear. While there are families with rare highly penetrant mutations in Cu/Zn superoxide dismutase 1 and several other genes that cause apparent Mendelian inheritance of the disease, most ALS occurs in families without another affected individual. However, twin studies suggest that all ALS has a substantial genetic basis. Herein, we estimate the genetic contribution to ALS in a clinically ascertained case series from the United States.
We used the database of the Emory ALS Center to ascertain individuals with ALS along with their family histories to determine the concordance among parents and offspring for the disease. We found that concordance for all parent-offspring pairs was low ( |
| doi_str_mv | 10.1371/journal.pone.0027985 |
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We used the database of the Emory ALS Center to ascertain individuals with ALS along with their family histories to determine the concordance among parents and offspring for the disease. We found that concordance for all parent-offspring pairs was low (<2%). With this concordance we found that ALS heritability, or the proportion of the disease explained by genetic factors, is between 40 and 45% for all likely estimates of ALS lifetime prevalence.
We found the lifetime risk of ALS is 1.1% in first-degree relatives of those with ALS. Environmental and genetic factors appear nearly equally important for the development of ALS.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0027985</identifier><identifier>PMID: 22132186</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Amyotrophic lateral sclerosis ; Amyotrophic Lateral Sclerosis - epidemiology ; Amyotrophic Lateral Sclerosis - genetics ; Biology ; Biomedical Research - statistics & numerical data ; Chromosomes ; Confidence intervals ; Demography ; Development and progression ; Disease ; Epidemiology ; Estimates ; Families & family life ; Family medical history ; Female ; Genetic aspects ; Genetic factors ; Genetics ; Heredity ; Heritability ; Humans ; Inheritance Patterns - genetics ; Inner city ; Liability ; Lubricants ; Male ; Medical research ; Medicine ; Middle Aged ; Mutation ; Neurology ; Offspring ; Parents ; Parents & parenting ; Population ; Progeny ; Registries - statistics & numerical data ; Studies ; Superoxide dismutase ; Superoxides ; Twins ; United States - epidemiology ; Zinc</subject><ispartof>PloS one, 2011-11, Vol.6 (11), p.e27985-e27985</ispartof><rights>COPYRIGHT 2011 Public Library of Science</rights><rights>2011. This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication. 2011</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c691t-8d0d706e2fbeaa36bf2365ab804b886f1f82dc35bcf02cf14f7854b934eabfe53</citedby><cites>FETCH-LOGICAL-c691t-8d0d706e2fbeaa36bf2365ab804b886f1f82dc35bcf02cf14f7854b934eabfe53</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/PMC3222666/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3222666/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79569,79570</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/22132186$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wingo, Thomas S</creatorcontrib><creatorcontrib>Cutler, David J</creatorcontrib><creatorcontrib>Yarab, Nicole</creatorcontrib><creatorcontrib>Kelly, Crystal M</creatorcontrib><creatorcontrib>Glass, Jonathan D</creatorcontrib><title>The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>The genetic basis of amyotrophic lateral sclerosis (ALS) is not entirely clear. While there are families with rare highly penetrant mutations in Cu/Zn superoxide dismutase 1 and several other genes that cause apparent Mendelian inheritance of the disease, most ALS occurs in families without another affected individual. However, twin studies suggest that all ALS has a substantial genetic basis. Herein, we estimate the genetic contribution to ALS in a clinically ascertained case series from the United States.
We used the database of the Emory ALS Center to ascertain individuals with ALS along with their family histories to determine the concordance among parents and offspring for the disease. We found that concordance for all parent-offspring pairs was low (<2%). With this concordance we found that ALS heritability, or the proportion of the disease explained by genetic factors, is between 40 and 45% for all likely estimates of ALS lifetime prevalence.
We found the lifetime risk of ALS is 1.1% in first-degree relatives of those with ALS. Environmental and genetic factors appear nearly equally important for the development of ALS.</description><subject>Amyotrophic lateral sclerosis</subject><subject>Amyotrophic Lateral Sclerosis - epidemiology</subject><subject>Amyotrophic Lateral Sclerosis - genetics</subject><subject>Biology</subject><subject>Biomedical Research - statistics & numerical data</subject><subject>Chromosomes</subject><subject>Confidence intervals</subject><subject>Demography</subject><subject>Development and progression</subject><subject>Disease</subject><subject>Epidemiology</subject><subject>Estimates</subject><subject>Families & family life</subject><subject>Family medical history</subject><subject>Female</subject><subject>Genetic aspects</subject><subject>Genetic factors</subject><subject>Genetics</subject><subject>Heredity</subject><subject>Heritability</subject><subject>Humans</subject><subject>Inheritance Patterns - genetics</subject><subject>Inner city</subject><subject>Liability</subject><subject>Lubricants</subject><subject>Male</subject><subject>Medical research</subject><subject>Medicine</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neurology</subject><subject>Offspring</subject><subject>Parents</subject><subject>Parents & parenting</subject><subject>Population</subject><subject>Progeny</subject><subject>Registries - 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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>Wingo, Thomas S</au><au>Cutler, David J</au><au>Yarab, Nicole</au><au>Kelly, Crystal M</au><au>Glass, Jonathan D</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry</atitle><jtitle>PloS one</jtitle><addtitle>PLoS One</addtitle><date>2011-11-22</date><risdate>2011</risdate><volume>6</volume><issue>11</issue><spage>e27985</spage><epage>e27985</epage><pages>e27985-e27985</pages><issn>1932-6203</issn><eissn>1932-6203</eissn><abstract>The genetic basis of amyotrophic lateral sclerosis (ALS) is not entirely clear. While there are families with rare highly penetrant mutations in Cu/Zn superoxide dismutase 1 and several other genes that cause apparent Mendelian inheritance of the disease, most ALS occurs in families without another affected individual. However, twin studies suggest that all ALS has a substantial genetic basis. Herein, we estimate the genetic contribution to ALS in a clinically ascertained case series from the United States.
We used the database of the Emory ALS Center to ascertain individuals with ALS along with their family histories to determine the concordance among parents and offspring for the disease. We found that concordance for all parent-offspring pairs was low (<2%). With this concordance we found that ALS heritability, or the proportion of the disease explained by genetic factors, is between 40 and 45% for all likely estimates of ALS lifetime prevalence.
We found the lifetime risk of ALS is 1.1% in first-degree relatives of those with ALS. Environmental and genetic factors appear nearly equally important for the development of ALS.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>22132186</pmid><doi>10.1371/journal.pone.0027985</doi><tpages>e27985</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Amyotrophic lateral sclerosis Amyotrophic Lateral Sclerosis - epidemiology Amyotrophic Lateral Sclerosis - genetics Biology Biomedical Research - statistics & numerical data Chromosomes Confidence intervals Demography Development and progression Disease Epidemiology Estimates Families & family life Family medical history Female Genetic aspects Genetic factors Genetics Heredity Heritability Humans Inheritance Patterns - genetics Inner city Liability Lubricants Male Medical research Medicine Middle Aged Mutation Neurology Offspring Parents Parents & parenting Population Progeny Registries - statistics & numerical data Studies Superoxide dismutase Superoxides Twins United States - epidemiology Zinc |
| title | The heritability of amyotrophic lateral sclerosis in a clinically ascertained United States research registry |
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