A Genome-Wide Search for Chromosomal Loci Linked to Mental Health Wellness in Relatives at High Risk for Bipolar Affective Disorder among the Old Order Amish
Bipolar affective disorder (BPAD; manicdepressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attemp...
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| Veröffentlicht in: | Proceedings of the National Academy of Sciences - PNAS 1998-12, Vol.95 (26), p.15531-15536 |
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| creator | Ginns, Edward I. St. Jean, Pamela Philibert, Robert A. Galdzicka, Marzena Damschroder-Williams, Patricia Thiel, Bonnie Long, Robert T. Ingraham, Loring J. Dalwaldi, Harnisha Murray, Melissa A. Ehlert, Melissa Paul, Sharon Remortel, Brian G. Patel, Ashima P. Maria C. H. Anderson Shaio, Cary Lau, Elaine Dymarskaia, Inna Martin, Brian M. Stubblefield, Barbara Falls, Kathleen M. Carulli, John P. Keith, Tim P. Cathy S. J. Fann Lacy, Lucy G. Allen, Cleona R. Hostetter, Abram M. Elston, Robert C. Schork, Nicholas J. Egeland, Janice A. Paul, Steven M. |
| description | Bipolar affective disorder (BPAD; manicdepressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5.22 × 10-4; SIBPAL Pempiricalvalue |
| doi_str_mv | 10.1073/pnas.95.26.15531 |
| format | Article |
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H. Anderson ; Shaio, Cary ; Lau, Elaine ; Dymarskaia, Inna ; Martin, Brian M. ; Stubblefield, Barbara ; Falls, Kathleen M. ; Carulli, John P. ; Keith, Tim P. ; Cathy S. J. Fann ; Lacy, Lucy G. ; Allen, Cleona R. ; Hostetter, Abram M. ; Elston, Robert C. ; Schork, Nicholas J. ; Egeland, Janice A. ; Paul, Steven M.</creator><creatorcontrib>Ginns, Edward I. ; St. Jean, Pamela ; Philibert, Robert A. ; Galdzicka, Marzena ; Damschroder-Williams, Patricia ; Thiel, Bonnie ; Long, Robert T. ; Ingraham, Loring J. ; Dalwaldi, Harnisha ; Murray, Melissa A. ; Ehlert, Melissa ; Paul, Sharon ; Remortel, Brian G. ; Patel, Ashima P. ; Maria C. H. Anderson ; Shaio, Cary ; Lau, Elaine ; Dymarskaia, Inna ; Martin, Brian M. ; Stubblefield, Barbara ; Falls, Kathleen M. ; Carulli, John P. ; Keith, Tim P. ; Cathy S. J. Fann ; Lacy, Lucy G. ; Allen, Cleona R. ; Hostetter, Abram M. ; Elston, Robert C. ; Schork, Nicholas J. ; Egeland, Janice A. ; Paul, Steven M.</creatorcontrib><description>Bipolar affective disorder (BPAD; manicdepressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5.22 × 10-4; SIBPAL Pempiricalvalue <3 × 10-5) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 × 10-3; SIBPAL Pempiricalvalue <1 × 10-3) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.</description><identifier>ISSN: 0027-8424</identifier><identifier>EISSN: 1091-6490</identifier><identifier>DOI: 10.1073/pnas.95.26.15531</identifier><identifier>PMID: 9861003</identifier><language>eng</language><publisher>United States: National Academy of Sciences of the United States of America</publisher><subject>Adult ; Alleles ; Amish culture ; Biological Sciences ; Bipolar disorder ; Bipolar Disorder - epidemiology ; Bipolar Disorder - genetics ; Christianity ; Chromosome Mapping ; Chromosomes ; Chromosomes, Human, Pair 4 ; DNA - blood ; Ethnic Groups - genetics ; Genetic inheritance ; Genetic Linkage ; Genetic loci ; Genetic Markers ; Genetics ; Genotype ; Humans ; Medical genetics ; Mental disorders ; Mental Health ; Middle Aged ; P values ; Pennsylvania - epidemiology ; Phenotypes ; Polymerase Chain Reaction ; Risk Factors ; Siblings</subject><ispartof>Proceedings of the National Academy of Sciences - PNAS, 1998-12, Vol.95 (26), p.15531-15536</ispartof><rights>Copyright 1993-1998 National Academy of Sciences</rights><rights>Copyright National Academy of Sciences Dec 22, 1998</rights><rights>Copyright © 1998, The National Academy of Sciences 1998</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c525t-2adab3ac6e3aa26030aa5f0132e1b090bc5ffdfcaa40aeca59db8a3b36c22cd3</citedby><cites>FETCH-LOGICAL-c525t-2adab3ac6e3aa26030aa5f0132e1b090bc5ffdfcaa40aeca59db8a3b36c22cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.pnas.org/content/95/26.cover.gif</thumbnail><linktopdf>$$Uhttps://www.jstor.org/stable/pdf/46412$$EPDF$$P50$$Gjstor$$H</linktopdf><linktohtml>$$Uhttps://www.jstor.org/stable/46412$$EHTML$$P50$$Gjstor$$H</linktohtml><link.rule.ids>230,314,723,776,780,799,881,27901,27902,53766,53768,57992,58225</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/9861003$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ginns, Edward I.</creatorcontrib><creatorcontrib>St. Jean, Pamela</creatorcontrib><creatorcontrib>Philibert, Robert A.</creatorcontrib><creatorcontrib>Galdzicka, Marzena</creatorcontrib><creatorcontrib>Damschroder-Williams, Patricia</creatorcontrib><creatorcontrib>Thiel, Bonnie</creatorcontrib><creatorcontrib>Long, Robert T.</creatorcontrib><creatorcontrib>Ingraham, Loring J.</creatorcontrib><creatorcontrib>Dalwaldi, Harnisha</creatorcontrib><creatorcontrib>Murray, Melissa A.</creatorcontrib><creatorcontrib>Ehlert, Melissa</creatorcontrib><creatorcontrib>Paul, Sharon</creatorcontrib><creatorcontrib>Remortel, Brian G.</creatorcontrib><creatorcontrib>Patel, Ashima P.</creatorcontrib><creatorcontrib>Maria C. H. Anderson</creatorcontrib><creatorcontrib>Shaio, Cary</creatorcontrib><creatorcontrib>Lau, Elaine</creatorcontrib><creatorcontrib>Dymarskaia, Inna</creatorcontrib><creatorcontrib>Martin, Brian M.</creatorcontrib><creatorcontrib>Stubblefield, Barbara</creatorcontrib><creatorcontrib>Falls, Kathleen M.</creatorcontrib><creatorcontrib>Carulli, John P.</creatorcontrib><creatorcontrib>Keith, Tim P.</creatorcontrib><creatorcontrib>Cathy S. J. Fann</creatorcontrib><creatorcontrib>Lacy, Lucy G.</creatorcontrib><creatorcontrib>Allen, Cleona R.</creatorcontrib><creatorcontrib>Hostetter, Abram M.</creatorcontrib><creatorcontrib>Elston, Robert C.</creatorcontrib><creatorcontrib>Schork, Nicholas J.</creatorcontrib><creatorcontrib>Egeland, Janice A.</creatorcontrib><creatorcontrib>Paul, Steven M.</creatorcontrib><title>A Genome-Wide Search for Chromosomal Loci Linked to Mental Health Wellness in Relatives at High Risk for Bipolar Affective Disorder among the Old Order Amish</title><title>Proceedings of the National Academy of Sciences - PNAS</title><addtitle>Proc Natl Acad Sci U S A</addtitle><description>Bipolar affective disorder (BPAD; manicdepressive illness) is characterized by episodes of mania and/or hypomania interspersed with periods of depression. Compelling evidence supports a significant genetic component in the susceptibility to develop BPAD. To date, however, linkage studies have attempted only to identify chromosomal loci that cause or increase the risk of developing BPAD. To determine whether there could be protective alleles that prevent or reduce the risk of developing BPAD, similar to what is observed in other genetic disorders, we used mental health wellness (absence of any psychiatric disorder) as the phenotype in our genome-wide linkage scan of several large multigeneration Old Order Amish pedigrees exhibiting an extremely high incidence of BPAD. We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5.22 × 10-4; SIBPAL Pempiricalvalue <3 × 10-5) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 × 10-3; SIBPAL Pempiricalvalue <1 × 10-3) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.</description><subject>Adult</subject><subject>Alleles</subject><subject>Amish culture</subject><subject>Biological Sciences</subject><subject>Bipolar disorder</subject><subject>Bipolar Disorder - epidemiology</subject><subject>Bipolar Disorder - genetics</subject><subject>Christianity</subject><subject>Chromosome Mapping</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 4</subject><subject>DNA - blood</subject><subject>Ethnic Groups - genetics</subject><subject>Genetic inheritance</subject><subject>Genetic Linkage</subject><subject>Genetic loci</subject><subject>Genetic Markers</subject><subject>Genetics</subject><subject>Genotype</subject><subject>Humans</subject><subject>Medical genetics</subject><subject>Mental disorders</subject><subject>Mental Health</subject><subject>Middle Aged</subject><subject>P values</subject><subject>Pennsylvania - epidemiology</subject><subject>Phenotypes</subject><subject>Polymerase Chain Reaction</subject><subject>Risk Factors</subject><subject>Siblings</subject><issn>0027-8424</issn><issn>1091-6490</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>1998</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkk2LE0EQhgdR1uzqXQSx8SBeJvbH9GQavMSoGyESWBf22NT01GQ6OzMduyfL-mP8r3Y-iB8HPRXU-7xFVfEmyTNGx4xOxNtND2Gs5JjnYyalYA-SEaOKpXmm6MNkRCmfpEXGs8fJeQhrSqmSBT1LzlSRM0rFKPkxJZfYuw7TG1sh-YrgTUNq58ms8a5zwXXQkoUzlixsf4sVGRz5gv0Qu3OEdmjIDbZtjyEQ25MrbGGwdxgIDGRuVw25suF2P--93bgWPJnWNZodQz7Y4HyFnkDn-hUZGiTLtiLLfW_a2dA8SR7V0AZ8eqwXyfWnj9ezebpYXn6eTRepkVwOKYcKSgEmRwHAcyoogKwpExxZSRUtjazrqjYAGQU0IFVVFiBKkRvOTSUukneHsZtt2WFl4nkeWr3xtgP_XTuw-k-lt41euTvNCzqZRPvro927b1sMg467m_gV6NFtg84Vo0wx_l-QTVgmhdqBr_4C127r-_gCzeNZQvAijxA9QMa7EDzWp4UZ1bt06F06tJKa53qfjmh58fuhJ8MxDlF_c9R3zpP6a4Kut2074P0Q0Zf_RiPx_ECsw-D8CcnyLL7iJ-Rm2kg</recordid><startdate>19981222</startdate><enddate>19981222</enddate><creator>Ginns, Edward I.</creator><creator>St. Jean, Pamela</creator><creator>Philibert, Robert A.</creator><creator>Galdzicka, Marzena</creator><creator>Damschroder-Williams, Patricia</creator><creator>Thiel, Bonnie</creator><creator>Long, Robert T.</creator><creator>Ingraham, Loring J.</creator><creator>Dalwaldi, Harnisha</creator><creator>Murray, Melissa A.</creator><creator>Ehlert, Melissa</creator><creator>Paul, Sharon</creator><creator>Remortel, Brian G.</creator><creator>Patel, Ashima P.</creator><creator>Maria C. 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We have found strong evidence for a locus on chromosome 4p at D4S2949 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5.22 × 10-4; SIBPAL Pempiricalvalue <3 × 10-5) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 × 10-3; SIBPAL Pempiricalvalue <1 × 10-3) that are linked to mental health wellness. These findings are consistent with the hypothesis that certain alleles could prevent or modify the clinical manifestations of BPAD and perhaps other related affective disorders.</abstract><cop>United States</cop><pub>National Academy of Sciences of the United States of America</pub><pmid>9861003</pmid><doi>10.1073/pnas.95.26.15531</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0027-8424 |
| ispartof | Proceedings of the National Academy of Sciences - PNAS, 1998-12, Vol.95 (26), p.15531-15536 |
| issn | 0027-8424 1091-6490 |
| language | eng |
| recordid | cdi_pubmed_primary_9861003 |
| source | Jstor Complete Legacy; MEDLINE; PubMed Central; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Adult Alleles Amish culture Biological Sciences Bipolar disorder Bipolar Disorder - epidemiology Bipolar Disorder - genetics Christianity Chromosome Mapping Chromosomes Chromosomes, Human, Pair 4 DNA - blood Ethnic Groups - genetics Genetic inheritance Genetic Linkage Genetic loci Genetic Markers Genetics Genotype Humans Medical genetics Mental disorders Mental Health Middle Aged P values Pennsylvania - epidemiology Phenotypes Polymerase Chain Reaction Risk Factors Siblings |
| title | A Genome-Wide Search for Chromosomal Loci Linked to Mental Health Wellness in Relatives at High Risk for Bipolar Affective Disorder among the Old Order Amish |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-03T16%3A10%3A16IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-jstor_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20Genome-Wide%20Search%20for%20Chromosomal%20Loci%20Linked%20to%20Mental%20Health%20Wellness%20in%20Relatives%20at%20High%20Risk%20for%20Bipolar%20Affective%20Disorder%20among%20the%20Old%20Order%20Amish&rft.jtitle=Proceedings%20of%20the%20National%20Academy%20of%20Sciences%20-%20PNAS&rft.au=Ginns,%20Edward%20I.&rft.date=1998-12-22&rft.volume=95&rft.issue=26&rft.spage=15531&rft.epage=15536&rft.pages=15531-15536&rft.issn=0027-8424&rft.eissn=1091-6490&rft_id=info:doi/10.1073/pnas.95.26.15531&rft_dat=%3Cjstor_pubme%3E46412%3C/jstor_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=201333286&rft_id=info:pmid/9861003&rft_jstor_id=46412&rfr_iscdi=true |