Abstract
Manic-depressive illness is a common psychiatric disorder with complex etiology that likely involves multiple genes and non-genetic influences. The uncertain path to gene discovery has spurred considerable debate over genetic findings and gene-finding strategies. In this article, I review the main findings, with a focus on: (1) putative linked loci on chromosomes 1q31–32, 4p16, 6pter–p24, 10p14, 10q21–26, 12q23–24, 13q31–32, 18p11, 18q21–23, 21q22, 22q11–13, and Xq24–28; and (2) association studies with candidate genes, dynamic mutations, mitochondrial mutations, and chromosomal aberrations. Although no gene has been identified, promising findings are emerging. I then discuss the challenges and opportunities ahead, with special emphasis on gene-finding methods—in particular, questions pertaining to phenotype definition, linkage and association mapping, gene markers, sampling, study population, multigene systems, lessons from other disorders, animal models, and bioinformatics. The progress to date, together with rapid advances in genomics, analytical and computational methods, and bioinformatics, holds promise for new insights into the genetics of manic-depression, in the new millennium.
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References
Rice JP Reich T Andreasen NC Endicott J Van Eerdewegh M Fishman R et alThe familial transmission of bipolar illness Arch Gen Psychiatry 1987 44 441 447
Spence MA Flodman PL Sadovnick AD Bailey-Wilson JE Ameli H Remick RA Bipolar disorder: evidence for a major locus Am J Med Genet 1995 60 370 376
Risch N Linkage strategies for genetically complex traits. I. Multilocus models Am J Hum Genet 1990 46 222 228
Craddock N Khodel V Van Eerdewegh P Reich T Mathematical limits for multilocus models Am J Hum Genet 1995 59 690 702
Nurnberger JI Jr Gershon ES Genetics of affective disorders. In: Paikel E (ed) Handbook of Affective Disorders Churchill Livingstone: London 1983 126 145
Martin JB Molecular genetics: applications to the clinical neurosciences Science 1987 238 765 772
Baron M Rainer JD Molecular genetics and human disease: implications for modern psychiatric research and practice Brit J Psychiatry 1988 152 741 753
Egeland JA Gerhard DS Pauls DL Sussex JN Kidd KK Allen CR et alBipolar affective disorder linked to DNA markers on chromosome 11 Nature 1987 325 783 787
Kelsoe JR Ginns EI Egeland JA Gerhard DS Goldstein AM Bale SJ et alRe-evaluation of the linkage relationship between chromosome 11p loci and the gene for bipolar affective disorder in the Old Order Amish Nature 1989 342 238 243
Baron M Is there a gene for manic-depressive illness on the long arm of the X chromosome? In: Gershon ES, Cloninger CR (eds) Genetic Approaches to Mental Disorders American Psychiatric Press: Washington, DC 1994 253 272
Baron M Freimer NF Risch N Lerer B Alexander JR Straub RE et alDiminished support for linkage between manic depressive illness and X-chromosome markers in three Israeli pedigrees Nature Genet 1993 3 49 55
Mendlewicz J Sevy S Brocas H Simon P Sharon F Legros S et alPolymorphic DNA marker on X chromosome and manic depression Lancet 1987 1 1230 1232
Baron M Genetic linkage in mental illness Nature 1990 346 618
Baron M Endicott J Ott J Genetic linkage in mental illness: limitations and prospects Brit J Psychiatry 1990 157 645 655
Risch N Genetic linkage and complex diseases, with special reference to psychiatric disorders Genet Epidemiol 1990 7 3 16
Pauls DL Behavioral disorders: lessons in linkage Nature Genet 1993 3 4 5
Cloninger RC Turning point in the design of linkage studies of schizophrenia Am J Med Genet 1994 54 83 92
Rutter M Psychiatric genetics: research challenges and pathways forward Am J Med Genet 1994 54 185 198
Lander E Kruglyak L Genetic dissection of complex traits: guidelines for interpreting and reporting linkage results Nature Genet 1995 11 241 247
Owen MJ Craddock N Modern molecular genetic approaches to complex traits: implications for psychiatric disorders Mol Psychiatry 1996 1 21 26
Risch N Botstein D A manic depressive history Nature Genet 1996 12 351 353
Baron M Genetic linkage and bipolar affective disorder: progress and pitfalls Mol Psychiatry 1997 2 200 210
Crow TJ DeLisi LE The chromosome workshops at the 5th International Congress of Psychiatric Genetics: the weight of the evidence from genome scans (Workshop reports, pp 63–129) Psychiatric Genet 1998 8 59 62
DeLisi LE Crow TJ Chromosome Workshops 1998: Current state of psychiatric linkage (Workshop reports, pp 219–286) Am J Med Genet 1998 88 215 218
DeLisi LE Craddock N Detera-Wadleigh S Foroud T Gejman P Kennedy JL et alUpdate of chromosomal locations for psychiatric disorders: report of the interim meeting of chromosome workshop chairpersons from the VII World Congress of Psychiatric Genetics, Monterey, California, October 14–18, 1999 Am J Med Genet 2000 96 434 449
Detera-Wadleigh SD Badner JA Berrettini WH Yoshikawa T Goldin LR Turner G et alA high-density genome scan detects evidence for a bipolar disorder susceptibility locus on 13q32 and other potential loci on 1q32 and 18p11.2 Proc Natl Acad Sci USA 1999 96 5604 5609
Turecki G Smith M Mari JJ Type I bipolar disorder associated with a fragile site on chromosome 1 Am J Med Genet 1995 60 179 182
Blackwood DHR He L Morris SW McLean A Whitton C Thomson L et alA locus for bipolar affective disorder on chromosome 4p Nature Genet 1996 12 427 30
Polymeropoulos MH Schaffer AA Scanning the genome with 1772 microsatellite markers in search of a bipolar disorder susceptibility gene Mol Psychiatry 1996 1 404 407
Ewald H Degn B Mors O Kruse TA Support for the possible locus on chromosome 4p16 for bipolar affective disorder Mol Psychiatry 1998 3 442 448
Ginns EI St Jean P Philibert RA Galszicka M Damschroder-Williams P Thiel B et alA 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 Proc Natl Acad Sci USA 1998 95 15531 15536
Ginns EI Ott J Egeland JA Allen CR Fann CSJ Pauls DL et alA genome-wide search for chromosomal loci linked to bipolar affective disorder in the Old Order Amish Nature Genet 1996 12 431 435
Turner WJ King S BPD, an autosomal dominant form of bipolar affective disorder Biol Psychiatry 1983 18 63 88
Foroud T Castelluccio PF Kollel DL Edenderg HJ Miller M Bowman E et alSuggestive evidence of a locus on chromosome 10p using the NIMH genetics initiative bipolar affective disorder pedigrees Am J Med Genet 2000 96 18 23
Rice JP Goate A Williams JT Bierut L Dorr D Wu W et alInitial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 1, 6, 8, 10, and 12 Am J Med Genet 1997 74 247 253
Cichon S Schmidt-Wolf G Schumacher J Muller DJ Hurter M Schulze TG et alA possible susceptibility locus for bipolar affective disorder in chromosomal region 10q25–26 Mol Psychiatry 2000 6 342 349
Kelsoe JR Spence MA Loetscher E Foguet M Sadovnick AD Remick RA et alA genome survey indicates a possible susceptibility locus for bipolar disorder on chromosome 22 Proc Natl Acad Sci USA 2001 98 585 590
Ewald H Kruse TA Mors O Evidence for oligogenes on chromosomes 12q24, 16p13.3, 4p16 and 10q in Danish families with bipolar affective disorder Mol Psychiatry 1999 4 S72
Morissette J Villeneuve A Bordeleau L Rochette D Laberge C Cagne B et alGenome-wide search for linkage of bipolar affective disorders in a very large pedigree derived from a homogeneous population in Quebec points to a locus of major effect on chromosome 12q23–24 Am J Med Genet 1999 88 567 587
Ewald H Degn B Mors O Kruse TA Significant linkage between bipolar affective disorder and chromosome 12q24 Psychiatr Genet 1998 8 131 140
Dawson E Parfitt E Roberts Q Daniels J Lim L Sham P et alLinkage studies of bipolar disorder in the region of the Darier's disease gene on chromosome 12q23–24.1 Am J Med Genet 1995 60 94 102
Craddock N Owen M Burge S Kurian B Thomas P McGuffin P Familial cosegregation of major affective disorder and Darier's disease (keratosis follicularis) Br J Psychiatry 1994 164 355 358
Jacobsen NJO Franks EKE Elvidge G Jones I McCandless F O'Donovan MC et alExclusion of the Darier's disease gene, ATP2A2, as a common susceptibility gene for bipolar disorder Mol Psychiatry 2001 6 92 97
Stine OC McMahon FJ Chen L-S Xu J Meyers DA MacKinnon D et alInitial genome screen for bipolar disorder in the NIMH genetics initiative pedigrees: chromosomes 2, 11, 13, 14, and X Am J Med Genet 1997 74 263 269
Berrettini WH Ferraro TN Goldin LR Weeks D Detera-Wadleigh S Nurnberger JI Jr et alPericentromeric chromosome 18 DNA markers and manic-depressive illness: evidence of a susceptibility gene Proc Natl Acad Sci USA 1994 91 5918 5921
Berrettini WH Ferraro TN Goldin LR Detera-Wadleigh SD Choi H Muniec D et alLinkage studies of bipolar illness Arch Gen Psychiatry 1997 54 32 39
Gershon ES Badner JA Ferraro TN Detera-Wadleigh SD Berrettini WH Am J Med Genet 1996 67 202 207
Stine OC Xu J Koskela R McMahon FJ Gschwend M Friddle C et alEvidence of linkage of bipolar disorder to chromosome 18 Am J Hum Genet 1995 57 1384 1394
MacKinnon DF Xu J McMahon FJ Simpson SG Stine OC McInnis MG et alBipolar disorder and panic disorder in families: an analysis of chromosome 18 data Am J Psychiatry 1998 155 829 831
Nothen MM Cichon S Rohleder H Hemmer S Franzek E Fritze J et alEvaluation of linkage of bipolar disorder to chromosome 18 in a sample of 57 German families Mol Psychiatry 1999 4 76 84
McMahon FJ Hopkins PJ Xu J McInnis MG Shaw S Cardon L et alLinkage of bipolar disorder to chromosome 18 markers in a new pedigree series Am J Hum Genet 1997 61 1397 1404
Freimer NB Reus VI Escamilla MA McInnis LA Spesny M Leon P et alGenetic mapping using haplotype, association and linkage methods suggests a locus for severe bipolar disorder (BPI) at 18q22–23 Nature Genet 1996 12 436 441
De bruyn A Souery D Mendelbaum K Mendlewicz J Van Broeckhoven C Linkage analysis of families with bipolar illness Biol Psychiatry 1996 39 679 688
Coon H Hoff M Holik J Hadley D Fang N Reimherr F et alAnalysis of chromosome 18 DNA markers in multiplex pedigrees with manic depression Biol Psychiatry 1996 39 689 696
Straub RE Lehner T Luo Y Loth JE Shao W Sharpe L et alA possible vulnerability locus for bipolar affective disorder on chromosome 21q22.3 Nature Genet 1994 8 291 296
Aita VM Liu J Knowles JA Terwilliger JD Baltazar R Grunn A et alA comprehensive linkage analysis of chromosome 21q22 supports prior evidence for a putative bipolar affective disorder locus Am J Hum Genet 1999 64 210 217
Liu J Juo SH Terwilliger JD Grunn A Tong X Brito M et alA follow-up linkage study supports evidence for a bipolar affective disorder locus on chromosome 21q22 Am J Med Genet 2001 105 189 194
Detera-Wadleigh SD Badner JA Goldin LR Berrettini WH Sanders AR Rollins DY et alAffected-sib-pair analyses reveal support of prior evidence for a susceptibility locus for bipolar disorder, on 21q Am J Hum Genet 1996 58 1279 1285
Smyth C Kalsi G Curtis D Brynjolfsson J O'Neill J Rifkin L et alTwo-locus admixture linkage analysis of bipolar and unipolar affective disorder supports the presence of susceptibility loci on chromosomes 11p12 and 21q22 Genomics 1997 39 271 278
Detera-Wadleigh SD Badner JA Yoshikawa T Sanders AR Goldin LR Turner G et alInitial genome scan of the NIMH genetics initiative bipolar pedigrees: chromosomes 4, 7, 9, 18, 19, 20, and 21q Am J Med Genet 1997 74 254 262
Kwok JB Adams LJ Salmon JA Donald JA Mitchell PB Schofield PR Nonparametric simulation-based statistical analyses for bipolar affective disorder locus on chromosome 21q22.3 Am J Med Genet 1999 88 99 102
Alda M Pharmacogenetics of lithium response in bipolar disorder J Psychiatry Neurosci 1999 24 154 158
Papolos DF Faedda GL Veit S Goldberg R Morrow B Kucherlapati R et alBipolar spectrum disorders in patients diagnosed with velo-cardio-facial syndrome: does the hemizygous deletion of chromosome 22q11 result in bipolar affective disorder? Am J Psychiatry 1996 153 1541 1547
Pulver AE Nestadt G Goldberg R Shprintzen RJ Lamacz M Wolyniec PS et alPsychotic illness in patients diagnosed with velo-cardio-facial syndrome and their relatives J Nerv Ment Dis 1994 182 476 478
Pekkarinen P Terwilliger J Bredbacka P-E Lonnqvist J Peltonen L Evidence of a predisposing locus to bipolar disorder on Xq24–27.1 in an extended Finnish pedigree Genome Res 1995 5 105 115
Lucotte GA Landoulsi A Berriche S David F Barbon MC Manic depressive illness is linked to factor IX in a French pedigree Ann Genet 1992 35 93 95
Bocchetta A Piccardi MP Martinelli V Quesada G Del Zompo M Maternal inheritance of manic depression in hemizygotes for the G6PD-Mediterranean mutation. Indirect evidence for Xq28 transmission in Sardinia Psychiatr Genet 1999 9 63 68
Turecki G Rouleau GA Mari J Joober R Morgan K Lack of association between bipolar disorder and tyrosine hydroxylase: a meta-analysis Am J Med Genet 1997 74 348 352
Souery D Lipp O Rivelli SK Massat I Serretti A Cavallini C et alTyrosine hydroxylase polymorphism and phenotypic heterogeneity in bipolar affective disorder: a multicenter association study Am J Med Genet 1999 88 527 532
Souery D Van Gestel S Massat I Blairy S Adolfsson R Blackwood D et alTryptophan hydroxylase polymorphism and suicidality in unipolar and bipolar affective disorders: a multicenter association study Biol Psychiatry 2001 49 405 409
O'Donovan MC Owen MJ Dynamic mutations and psychiatric genetics Psychol Med 1996 26 1 6
Lindblad K Nylander P-O De bruyn A Sourey D Zander C Engstrom C et alDetection of expanded CAG repeats in bipolar affective disorder using the repeat expansion detection (RED) method Neurobiol Dis 1995 2 55 62
Lindblad K Nylander P-O Zander C Yuan Q-P Stahle L Engstrom C et alTwo commonly expanded CAG/CTG repeat loci: involvement in affective disorders? Mol Psychiatry 1998 3 405 410
O'Donovan MC Guy C Craddock N Murphy KC Cardno AG Jones LA et alExpanded CAG repeats in schizophrenia and bipolar disorder Nature Genet 1995 10 380 381
O'Donovan MC Guy C Craddock N Bowen T Mckeon P Macedo A et alConfirmation of association between expanded CAG/CTG repeats and both schizophrenia and bipolar disorder Psychol Med 1996 26 145 153
Oruc L Lindblad K Verheyen GR Ahlberg S Jakovljevic M Ivezic S et alCAG repeat expansion in bipolar and unipolar diorders Am J Hum Genet 1997 60 730 732
Kato T Winokur G Coryell W Keller MB Endicott J Rice J Parent-of-origin effect in transmission of bipolar disorder Am J Med Genet 1996 67 546 550
McMahon FJ Stine OC Meyers DA Simpson SA DePaulo JR Patterns of maternal transmission in bipolar affective disorder Am J Hum Genet 1995 56 1277 1286
Kato T Stine OC McMahon FJ Crow RR Increased levels of a mitochondrial DNA deletion in the brain of patients with bipolar disorder Biol Psychiatry 1997 42 871 885
Miyaoka H Suzuki Y Taniyama M Miyaoka Y Shishikura K Kamijima K et alMental disorders in diabetic patients with mitochondrial transfer RNA (Leu)(UUR) mutation at position 3243 Biol Psychiatry 1997 15 524 526
Kirk R Furlong RA Amos W Cooper G Rubinsztein JS Walsh C et alMitochondrial genetic analyses suggest selection against maternal lineages in bipolar affective disorder Am J Hum Genet 1999 65 508 518
Gigoroiou-Serbanescu M Martinez M Nothen MM Propping P Milea S Mihailescu R et alPatterns of parental transmission and familial aggregation models in bipolar affective disorder Am J Med Genet 1998 81 397 401
Craddock N Owen M Chromosomal aberrations and bipolar affective disorder Br J Psychiatry 1994 164 507 512
Bassette AS Chromosomal aberration and schizophrenia Br J Psychiatry 1992 161 323 334
Turecki G Alda M Grof P Martin R Cavazzoni PA Duffy A et alNo association between chromosome 18 markers and lithium-responsive affective disorders Psychiatry Res 1996 63 17 23
Turecki G Grof P Cavazzoni P Duffy A Grof E Ahrens B et alEvidence for a role for phospolipase c-y1 in the pathogenesis of bipolar disorder Mol Psychiatrty 1998 3 534 538
Alda M Turecki G Grof E Cavazzoni P Duffy A Zvolsky P et alGenome scan of bipolar disorder using a pharmacogenetic strategy Mol Psychiatry 1999 4 (Suppl 1) 16(Abstract)
McGuffin P Farmer A Harvey I A polydiagnostic application of operational criteria in studies of psychotic illness: development and reliability of the OPCRIT system Arch Gen Psychiatry 1991 48 764 770
Rice JP Endicott J Knesevich MA Rochberg N The estimation of diagnostic sensitivity using stability data: an application to major depressive disorders J Psychiatr Res 1987 21 337 345
Baron M Hamburger R Sandkuyl LA Risch N Mandel B Endicott J et alThe impact of phenotypic variation on genetic analysis: application to X-linkage in manic-depressive illness Acta Psychiatr Scand 1990 82 196 203
Turecki G Rouleau G Morgan K Modeling the phenotype in parametric linkage analysis of bipolar disorder Genet Epidemiol 1997 14 687 691
Van Eerdewegh P Santangelo SL Lee H Laird NM Blacker D Probabilistic diagnosis in linkage analysis of bipolar disorder: putting weights on the fringe Genet Epidemiol 1997 14 693 698
Levinson DF Linkage analysis of complex disorders with multiple phenotypic categories: simulation studies and application to bipolar disorder data Genet Epidemiol 1997 14 653 658
Baron M Genetics of schizophrenia and the new millennium: progress and pitfalls Am J Hum Genet 2001 68 299 312
Leal SM Phenotypes and genetic analysis of psychiatric and neuropsychiatric traits Am J Med Genet 2001 105 4 7
Myles-Worsley M Coon H McDowell J Brenner C Hoff M et alLinkage of a composite inhibitory phenotype to a chromosome 22q locus in eight Utah families Am J Med Genet 1999 88 544 550
Murphy FC Sahakian BJ Neuropsychology of bipolar disorder Brit J Psychiatry 2001 178 (Suppl 41) S120 S127
Baumann B Bogerts B Neuroanatomical studies on bipolar disorder Brit J Psychiatry 2001 178 (Suppl. 41) S142 S147
Baron M Gruen R Asnis L Kane J Schizoaffective illness, schizophrenia and affective disorders: morbidity risk and genetic transmission Acta Psychiatr Scand 1983 65 253 262
Gershon ES DeLisi LE Hamovit J Nurnberger JI Jr Maxwell ME Schreiber J et alA controlled family study of chronic psychoses: schizophrenia and schizoaffective disorder Arch Gen Psychiatry 1988 45 328 336
Crow TJ The continuum of psychosis and its genetic origins Brit J Psychiatry 1990 156 788 797
Maier W Lichtermann D Minges J Hallmayer J Heun R Benkert O et alContinuity and discontinuity of affective disorders and schizophrenia: results of a controlled family study Arch Gen Psychiatry 1993 50 871 883
Berrettini WH Are schizophrenic and bipolar disorders related? A review of family and molecular studies Biol Psychiatry 2000 48 531 538
Hovatta I Varilo T Suvisaari J Terwilliger JD Ollikainen V Arajarvi R et alA genomewide screen for schizophrenia genes in an isolated Finnish subpopulation, suggesting multiple susceptibility loci Am J Hum Genet 1999 65 1114 1124
Faraone SV Matise T Svrakic D Pepple J Malaspina D Suarez B et alGenome scan of European-American schizophrenia pedigrees: results of the NIMH genetics initiative and millennium consortium Am J Med Genet 1998 81 290 295
Straub RE MacLean CJ Martin RB Ma Y Myakishev MV Harris-Kerr C et alA schizophrenia locus may be located in region 10p15-p11 Am J Med Genet 1998 81 296 301
Schwab SG Hallmayer J Albus M Lerer B Eckstein GN Borrmann M et alA genome-wide autosomal screen for schizophrenia susceptibility loci in 71 families with affected siblings: support for loci on chromosome 10p and 6 Mol Psychiatry 2000 5 638 649
Blouin J-L Dombroski BA Nath SK Lasseter VK Wolyniec PS Nestadt G et alSchizophrenia susceptibility loci on chromosomes 13q32 and 8p21 Nature Genet 1998 20 70 73
Brzustowicz LM Honer WG Chow EWC Little D Hogan J Hodgkinson K et alLinkage of familial schizophrenia to chromosome 13q32 Am J Hum Genet 1999 65 1096 1103
Schwab SG Hallmayer J Lerer B Albus M Borrmann M Honig S et alSupport for a chromosome 18p locus conferring susceptibility to functional psychoses in families with schizophrenia, by association and linkage analysis Am J Hum Genet 1998 63 1139 1152
Pulver AE Karayiorgou M Wolyniec PS Lasseter VK Kasch L Nestadt G et alSequential strategy to identify a susceptibility gene for schizophrenia: report of potential linkage on chromosome 22q12-q13.1: part 1 Am J Med Genet 1994 54 36 43
Lasseter VK Pulver LE Wolyniec PS Nestadt G Meyers D Karayiorgou M et alFollow-up report of potential linkage to schizophrenia on chromosome 22q: part 3 Am J Med Genet 1994 60 172 173
Vieland VJ Hodge SE Greenberg DA Adequacy of single-locus approximations for linkage analyses of oligogenic traits Genet Epidemiol 1992 9 45 59
Hauser ER Bohnke M Guo S-W Risch N Affected sib pair interval mapping and exclusion for complex genetic traits Genet Epidemiol 1996 13 117 137
Elston RC Guo X Williams LV Two-stage global search designs for linkage analysis using pairs of affected relatives Genet Epidemiol 1996 13 535 558
Holmans P Craddock N Efficient strategies for genome scanning using maximum-likelihood affected sib-pair analysis Am J Hum Genet 1997 60 657 666
Greenberg DA Hodge SE Vieland VJ Spence MA Reply to Farrall Am J Hum Genet 1997 61 254 255
Greenberg DA Hodge SE Vieland VJ Spence M Reply to Kruglyak Am J Hum Genet 1998 62 202 204
Goldgar DE Easton DF Optimal strategies for mapping complex diseases in the presence of multiple loci Am J Hum Genet 1997 60 1222 1232
Kruglyak L Nonparametric linkage tests are model free Am J Hum Genet 1997 61 254 255
Curtis D Efficient strategies for genome scanning with affected sib-pairs Am J Hum Genet 1998 62 204 205
Terwilliger JD Linkage analysis is model-basedIn: Armitage P, Colton T (eds)Encyclopedia of Biostatitics Vol 3 Wiley, UK 1998pp2279 2291
Baron M Optimal ascertainment strategies to detect linkage to common disease alleles Am J Hum Genet 1999 64 1243 1246
Baron M Linkage mapping of bipolar affective disorder Am J Med Genet 2000 96 881 883
Knowles JA Rao PA Cox-Matise T Loth JE de Jesus GM Levine L et alNo evidence for significant linkage between bipolar affective disorder and chromosome 18 pericentromeric markers in a large series of multiplex extended pedigrees Am J Hum Genet 1998 62 916 924
Friddle C Koskela R Ranade K Herebert J Cargill M Clark CD et alFull-genome scan for linkage in 50 families segregating the bipolar affective disease phenotype Am J Hum Genet 2000 66 205 215
Kornberg JR Brown JL Sadovnick AD Remick RA Keck PE Jr McElroy SL et alEvaluating the parent-of-origin effect in bipolar affective disorder Is a more penetrant subtype transmitted paternally? J Affect Dis 2000 59 183 192
Jorde LB Linkage disequilibrium and the search for complex disease genes Genome Res 2000 10 1435 1444
Ott J Hoh J Statistical approaches to gene mapping Am J Hum Genet 2000 67 289 294
Hodge SE Model-free vs model-based linkage analysis: a false dichotomy? Am J Med Genet 2001 105 62 64
Crowe RR Candidate genes in psychiatry: an epidemiological perspective Am J Med Genet 1993 48 74 77
Kidd KK Association of disease with genetic markers: déjà vu all over again Am J Med Genet 1993 48 71 72
Carey G Genetic association study in psychiatry: analytical evaluation and a recommendation Am J Med Genet 1994 54 311 317
Owen MJ Holmans P McGuffin P Association studies in psychiatric genetics Mol Psychiatry 1997 2 270 273
Paterson AD Case-control association studies in complex traits—the end of an era? Mol Psychiatry 1997 2 277 278
Baron M Association studies in psychiatry: a season of discontent Mol Psychiatry 1997 2 278 281
Baron M Candidate genes and behavioral traits—candidly! Arch Gen Psychiatry 1999 56 582 583
Baron M The search for complex disease genes: fault by linkage or fault by association? Mol Psychiatry 2001 6 143 149
Concannon P Gogolin-Ewens KJ Hinds DA Wapelhorst B Morrison VA Stirling B et alA second-generation screen of the human genome for susceptibility to insulin-dependent diabetes mellitus Nat Genet 1998 19 292 296
Scott WK Pericak-Vance MA Haines JL Genetic analysis of complex diseases Science 1997 275 1327
Risch N Merikangas K The future of genetic studies of complex human diseases Science 1996 273 1516 1517
Risch N Searching for genetic determinants in the new millennium Nature 2000 405 847 856
Kruglyak L What is significant in whole-genome linkage disequilibrium studies? Am J Hum Genet 1997 61 810 812
Terwilliger JD Weiss KM Linkage disequilibrium mapping of complex disease: fantasy or reality? Curr Opin Biotechnol 1998 9 578 594
Weiss KM Terwilliger JD How many diseases does it take to map a gene with SNPs? Nature Genet 2000 26 151 157
Trembath RC Clough RL Rosbotham JL Jones AB Camp RDR Frodsham A et alIdentification of a major susceptibility locus on chromosome 6p and evidence for further disease loci revealed by a two-stage genomewide search in psoriasis Hum Mol Genet 1997 6 813 820
Kainulainen K Perola M Terwilliger J Kaprio J Koskenvuo M Syvanen A-C et alEvidence for involvement of the type 1 angiotensin II receptor locus in essential hypertension Hypertension 1999 33 844 849
Collins FS Guyer MS Chakravarti A Variations on a theme: cataloging human DNA sequence variation Science 1997 278 1580 1581
Wang DG Fan J-B Siao C-J Berno A Young P Sapolsky R et alLarge-scale identification, mapping, and genotyping of single-nucleotide polymorphisms in the human genome Science 1998 280 1077 1082
Schork NJ Fallin D Lanchbury S Single nucleotide polymorphisms and the future of genetic epidemiology Clin Gene 2000 58 250 264
Kruglyak L Prospects for whole-genome linkage disequilibrium mapping of common disease genes Hum Genet 1998 22 139 144
Boehnke M A look at linkage disequilibrium Nat Genet 2000 25 246 247
Barcellos LF Klitz W Field L Tobias R Bowcock AM Wilson R et alAssociation mapping of disease loci by use of a pooled DNA genomic screen Am J Hum Genet 1997 61 734 747
Cargill M Altshuler D Ireland J Sklar P Ardlie K Patil N et alCharacterization of single-nucleotide polymorphisms in coding regions of human genes Nature Genet 1999 22 231 238
Sklar P SNPs and neuropsychiatric disorders: discovery and genotyping Am J Med Genet 2000 96 457
Sun YP Zhang L Johnston NL Torrey EF Yolken RH Serial analysis of gene expression in the frontal cortex of patients with bipolar disorder Brit J Psychiatry 2001 178 (Suppl 41) S137 S141
Niculescu AB Segal DS Kuczenski R Barrett T Hauger RI Kelsoe JR Identifying a series of candidate genes for mania and psychosis: a convergent functional genomics approach Physiol Genomics 2000 9 83 91
Suarez BK Hampe CL Van Eerdewegh P Problems of replicating linkage claims in psychiatry. In: Gershon ES, Cloninger CR (eds) Genetic Approaches to Mental Disorders American Psychiatric Press: Washington, DC 1994 23 46
Rice J Genetic analysis of bipolar disorder: summary of GAW10 Genet Epidemiol 1997 14 549 561
Kelsoe JR Sadovnick AD Kristbjarnarson H Bergesch P Mroczkowski-Parker Z Rapaport MH et alPossible locus for bipolar disorder near the dopamine receptor on chromosome 5 Am J Med Genet 1996 67 553 540
Greenwood TA Alexander M Keck PE McElroy S Sadovnick AD Remick RA et alEvidence for linkage disequilibrium between the dopamine transporter and bipolar disorder Am J Med Genet 2001 105 145 151
Rice JP The role of meta-analysis in linkage studies of complex traits Am J Med Genet 1997 74 112 114
Gu C Province M Todorov A Rao DC Meta-analysis methodology for combining non-parametric sibpair linkage results: genetic homogeneity and identical markers Genet Epidemiol 1998 15 609 626.32
Wise LH Lanchbury JJ Lewis CM Meta-analysis of genome searches Ann Hum Genet 1999 63 263 272
Peltonen L Positional cloning of disease genes: advantages of genetic isolates Hum Hered 2000 50 66 75
Eaves IA Merriman TR Barber RA Nutland S Tuomilehto-Wolf E Tuomilehto J et alThe genetically isolated populations of Finland and Sardinia may not be a panacea for linkage disequilbrium mapping of common disease genes Nat Genet 2000 25 320 323
Reich DE Cargill M Bolk S Ireland J Sabeti PC Richter DJ et alLinkage disequilibrium in the human genome Nature 2001 411 199 204
Buhler J Owerbach D Schaffer AA Kimmel M Gabbay KH Linkage analysis in type I diabetes mellitus using CASPAR, a software and statistical program for conditional analysis of polygenic diseases Hum Hered 1997 47 211 222
Cox NJ Frigge M Nicolae DL Concannon P Hanis CL Bell GI et alLoci on chromosomes 2 (NIDDM1) and 15 interact to increase susceptibility to diabetes in Mexican Americans Nat Genet 1999 21 213 215
Horikawa Y Oda N Cox NJ Li X Orho-Melander M Hara M et alGenetic variation in the gene encoding calpain-10 is associated with type 2 diabetes mellitus Nature Genet 2000 26 163 175
Lucek P Hanke J Reich J Solla S Ott J Multi-locus nonparametric linkage analysis of complex trait loci with neural networks Hum Genet 1998 48 275 284
Hoh JJ Ott J Complex inheritance and localizing disease genes Hum Hered 2000 50 85 89
Ott J Neural networks and disease association studies Am J Med Genet 2001 105 60 61
Rao DC Province MA The future of path analysis, segregation analysis, and combined models for genetic dissection of complex traits Hum Hered 2000 50 34 42
Tsao BP Cantor RM Kalunian KC Chen C-J Badsha H Singh R et alEvidence for linkage of a candidate chromosome 1 region to human systemic lupus erythematosus J Clin Invest 1997 99 725 731
Tsao BP Cantor RM Grossman JM Shen N Teophilov NT Wallace DJ et alPARP alleles within the linked chromosomal region are associated with systemic lupus erythematosus J Clin Invest 1999 103 1135 1140
Tavtigian SV Simard J Teng DHF Abtin V Baumgard M Beck A et alA candidate prostate cancer susceptibility gene at chromosome 17p Nature Genet 2001 27 172 180
Stoll M Kwitek-Black AE Cowly AW Jr Harris EL Harrap SB Krieger JE et alNew target regions for human hypertension via comparative genomics Genome Res 2000 10 473 482
Flint J Corlev R DeFries JC Fulker DW Gay JA Miller S et alA simple genetic basis for a complex psychological trait in laboratory mice Science 1995 269 1432 435
Caldarone B Saavedra C Tartaglia K Wehner JM et alQuantitative trait loci analysis affecting contextual conditioning in mice Nature Genet 1997 17 335 337
Rogers J Mahaney MC Witte SM Nair S Newman D Wedel S et alA genetic linkage map of the baboon (Papio hamadryas) genome based on human microsatellite polymorphisms Genomics 2000 67 237 247
Masys DR Welsh JB Lynn FJ Gribskov M Klacansky I Corbeil J Use of keyword hierarchies to interpret gene expression patterns Bioinformatics 2001 17 319 326
Jenssen T-K Laegreid A Komorowski J Hovig E A literature network of human genes for high-throughput analysis of gene expression Nature Genet 2001 28 21 28
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Baron, M. Manic-depression genes and the new millennium: poised for discovery. Mol Psychiatry 7, 342–358 (2002). https://doi.org/10.1038/sj.mp.4000998
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A genome screen of 35 bipolar affective disorder pedigrees provides significant evidence for a susceptibility locus on chromosome 15q25-26
Molecular Psychiatry (2009)
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Association analysis of monoamine oxidase A gene and bipolar affective disorder in Han Chinese
Behavioral and Brain Functions (2008)
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Use of phenotypic covariates in association analysis by sequential addition of cases
European Journal of Human Genetics (2006)
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Psychosis and the genetic spectrum of bipolar disorder: evidence from linkage analysis
Molecular Psychiatry (2006)