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

Edward I. Ginns, Pamela St. Jean, Robert A. Philibert, Marzena Galdzicka, Patricia Damschroder-Williams, Bonnie Thiel, Robert T. Long, Loring J. Ingraham, Harnisha Dalwaldi, Melissa A. Murray, Melissa Ehlert, Sharon Paul, Brian G. Remortel, Ashima P. Patel, Maria C.H. Anderson, Cary Shaio, Elaine Lau, Inna Dymarskaia, Brian M. Martin, Barbara StubblefieldKathleen M. Falls, John P. Carulli, Tim P. Keith, Cathy S.J. Fann, Lucy G. Lacy, Cleona R. Allen, Abram M. Hostetter, Robert C. Elston, Nicholas J. Schork, Janice A. Egeland, Steven M. Paul

Research output: Contribution to journalArticle

70 Scopus citations

Abstract

Bipolar affective disorder (BPAD; manic-depressive 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 x 10-1-4; SIBPAL P(empirical) value <3 x 10-5) and suggestive evidence for a locus on chromosome 4q at D4S397 (maximum GENEHUNTER-PLUS nonparametric linkage score = 3.29, P = 2.57 x 101-3; SIBAL P(empirical) value < 1 x 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.

Original languageEnglish (US)
Pages (from-to)15531-15536
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume95
Issue number26
DOIs
StatePublished - Dec 22 1998

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    Ginns, E. I., St. Jean, P., Philibert, R. A., Galdzicka, M., Damschroder-Williams, P., Thiel, B., Long, R. T., Ingraham, L. J., Dalwaldi, H., Murray, M. A., Ehlert, M., Paul, S., Remortel, B. G., Patel, A. P., Anderson, M. C. H., Shaio, C., Lau, E., Dymarskaia, I., Martin, B. M., ... Paul, S. M. (1998). 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. Proceedings of the National Academy of Sciences of the United States of America, 95(26), 15531-15536. https://doi.org/10.1073/pnas.95.26.15531