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

被引:70
作者
Ginns, EI
St Jean, P
Philibert, RA
Galdzicka, M
Damschroder-Williams, P
Thiel, B
Long, RT
Ingraham, LJ
Dalwaldi, H
Murray, MA
Ehlert, M
Paul, S
Remortel, BG
Patel, AP
Anderson, MCH
Shaio, C
Lau, E
Dymarskaia, I
Martin, BM
Stubblefield, B
Falls, KM
Carulli, JP
Keith, TP
Fann, CSJ
Lacy, LG
Allen, CR
Hostetter, AM
Elston, RC
Schork, NJ
Egeland, JA
Paul, SM
机构
[1] NIMH, Clin Neurosci Branch, Intramural Res Program, Bethesda, MD 20892 USA
[2] Case Western Reserve Univ, Dept Epidemiol & Biostat, Cleveland, OH 44109 USA
[3] Genome Therapeut Corp, Waltham, MA 02154 USA
[4] Albert Einstein Coll Med, Dept Epidemiol & Social Med, Bronx, NY 10467 USA
[5] Univ Miami, Sch Med, Dept Psychiat, Miami, FL 33136 USA
[6] Indiana Univ, Sch Med, Dept Psychiat, Indianapolis, IN 46285 USA
[7] Indiana Univ, Sch Med, Dept Pharmacol, Indianapolis, IN 46285 USA
[8] Indiana Univ, Sch Med, Dept Toxicol, Indianapolis, IN 46285 USA
[9] Eli Lilly & Co, Lilly Res Labs, Indianapolis, IN 46285 USA
关键词
D O I
10.1073/pnas.95.26.15531
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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 D4S2939 (maximum GENEHUNTER-PLUS nonparametric linkage score = 4.05, P = 5.22 x 10(-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 10(-3); SIBPAL 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.
引用
收藏
页码:15531 / 15536
页数:6
相关论文
共 40 条
[1]   CHROMOSOME-18 DNA MARKERS AND MANIC-DEPRESSIVE ILLNESS - EVIDENCE FOR A SUSCEPTIBILITY GENE [J].
BERRETTINI, WH ;
FERRARO, TN ;
GOLDIN, LR ;
WEEKS, DE ;
DETERAWADLEIGH, S ;
NURNBERGER, JI ;
GERSHON, ES .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1994, 91 (13) :5918-5921
[2]   A locus for bipolar affective disorder on chromosome 4p [J].
Blackwood, DHR ;
He, L ;
Morris, SW ;
McLean, A ;
Whitton, C ;
Thomson, M ;
Walker, MT ;
Woodburn, K ;
Sharp, CM ;
Wright, AF ;
Shibasaki, Y ;
StClair, DM ;
Porteous, DJ ;
Muir, WJ .
NATURE GENETICS, 1996, 12 (04) :427-430
[3]  
BOEHNKE M, 1991, AM J HUM GENET, V48, P22
[4]   A metric map of humans: 23,500 loci in 850 bands [J].
Collins, A ;
Frezal, J ;
Teague, J ;
Morton, NE .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1996, 93 (25) :14771-14775
[5]   PROTECTIVE EFFECT OF APOLIPOPROTEIN-E TYPE-2 ALLELE FOR LATE-ONSET ALZHEIMER-DISEASE [J].
CORDER, EH ;
SAUNDERS, AM ;
RISCH, NJ ;
STRITTMATTER, WJ ;
SCHMECHEL, DE ;
GASKELL, PC ;
RIMMLER, JB ;
LOCKE, PA ;
CONNEALLY, PM ;
SCHMADER, KE ;
SMALL, GW ;
ROSES, AD ;
HAINES, JL ;
PERICAKVANCE, MA .
NATURE GENETICS, 1994, 7 (02) :180-184
[6]   APPROACHES TO THE GENETICS OF AFFECTIVE-DISORDERS [J].
CRADDOCK, N ;
MCGUFFIN, P .
ANNALS OF MEDICINE, 1993, 25 (04) :317-322
[7]  
Drigalenko EI, 1997, GENET EPIDEMIOL, V14, P779, DOI 10.1002/(SICI)1098-2272(1997)14:6<779::AID-GEPI36>3.0.CO
[8]  
2-L
[9]   BIPOLAR AFFECTIVE-DISORDERS LINKED TO DNA MARKERS ON CHROMOSOME-11 [J].
EGELAND, JA ;
GERHARD, DS ;
PAULS, DL ;
SUSSEX, JN ;
KIDD, KK ;
ALLEN, CR ;
HOSTETTER, AM ;
HOUSMAN, DE .
NATURE, 1987, 325 (6107) :783-787
[10]  
Egeland JA, 1994, GENETIC STUDIES AFFE, P70