全面性癫(癎)伴热性惊厥附加症的临床与分子遗传学研究

目的 探讨全面性癫痫伴热性惊厥附加症（generalized epilepsy with febrile seizures plus，GEFS＋）的临床特点与分子遗传学特征。方法 收集1个GEFS＋家系所有成员的血样标本，选择3种候选基因（SCN1B、SCN1A、GABRG2）附近的11个微卫星标记物D19S414、D19S220、D19S902、D2S156、D2S142、D2S2330、D2S335、D2S364、D5s436、D5S422和D5S400，应用PCR得到扩增产物片段，根据相应产物大小的不同，得到每个样本的基因型；用连锁分析软件的MLINK程序计算每个标记的LOD值，根据两点间的LOD值判断连锁关系，探讨GEFS＋的可能致病基因与染色体19q13．1、2q24以及5q31．1-q33．1区域的连锁关系。连锁分析限定性定位后再进行GABRG2基因突变分析。结果 （1）GEFS＋家系临床特征：家系成员4代共20人。第Ⅱ～Ⅳ代中患者6例（男女各3例）；发作表型为热性惊厥（FS）1例、热性惊厥附加症（FS＋）3例、Fs＋伴失神发作1例，发作类型不详1例，未见严重发作类型。（2）GEFS＋基因连锁分析结果：①D2S335因不能进行基因分型，给予舍弃；②D19S和D2S多个LOD值小于0，在重组率为0．0时D19S220、D19s902、D2S364处的LOD值均小于-2；D19S414、D2S142、D2S156、D2S2330、D5S422处的LOD值小于0，基本可以排除连锁关系；③D5S436、D5$400处的LOD值在重组率为0．0时大于-2，但小于3，既不能排除也不能肯定其连锁关系；该家系致病基因与报道的GEFS＋定位区域19q13．1和2q24区域没有连锁关系；与5q31．1．q33．1区域的连锁关系有待于进一步明确。（3）GABRG2基因的测序结果（先证者）：显示11外显子一处同义突变（c．1420C〉T），未见GABRG2基因致病突变。结论 该GEFS＋家系呈现不同的临床表型，其疾病基因与3种候选基因SCN1A、SCN1B、GABARG2的突变无关；表明GFFS＋具有表型的异质性与遗传的异质性，其病因学有待进一步研究。     

硫氧还原蛋白结合蛋白基因与精神分裂症的潜在关系

精神分裂症是精神疾病中最严重、危害最大的疾病，人群终身患病率高达13‰，目前，精神分裂症的病理机制尚不完全明了。至今已至少发现17个染色体区域上的遗传标记可能与精神分裂症有关。其中，lq21—22、6p22—24、及13q32-34是获得最多证据支持的区域，被认为最有希望找到精神分裂症的遗传因子     

20个精神分裂症同胞对家系N-甲基-D-天冬氨酸受体基因的连锁研究

目的：了解兴奋性氨基酸N-甲基-D-天冬氨酸（NMDA）受体基因与精神分裂症的连锁关系。方法：选取NMDA受体4个亚单位基因附近的微卫星标记，对20个精神分裂症受累同胞对家系共83个个体作基因分型，其中男43名，女40名，患病同胞对20对40例。采用受累家系成员法（ASP）对分型资料进行连锁分析。结果：NMDA受体亚单位基因NMDAB2A位点16p13.2附近的微卫星标记D16s3075的优势对数值（LOD值）为0.81，NMDAR2B位点12p12附近的标记D12s1617的LOD值为0.47，其余位点附近的10个微卫星标记与前2个标记一样，其LOD值均未达到提示性连锁的阈值（LOD=2.2）。结论：未能肯定NMDA受体基因与精神分裂症的连锁关系，但亦不能排除该基因与精神分裂症的相关性。     

人类6号染色体上精神分裂症候选基因研究进展

家系调查、双生子及寄养子研究证实遗传因素在精神分裂症病因中起重要作用,嗣后人们应用分子遗传学方法,探讨了众多染色体区域及候选基因与精神分裂症之间关系,其中主要集中于染色体6p、22q、8p、13q及单胺类功能基因。由于研究结果很难在不同的样本或人群中被重复,迄今为止精神分裂症的致病基因尚未明确。近年来,国内外学者就6号染色体及连锁区域内基因与精神分裂症之间关系,进行了诸多探索,并获得较多阳性支持的证据,值得我们关注。     

N-甲基-D-天冬氨酸受体2A亚单位基因与精神分裂症的连锁分析

目的了解N-甲基-D-天冬氨酸受体2A亚单位基因(NR2A)与精神分裂症的连锁关系。方法选取NR2A亚单位基因所在区域的3个微卫星标志[D16s407、D16s3075及NR2A启动子区的1个(GT)重复序列]，对中国汉族81个独立精神分裂症受累同胞对及其家系成员共324个个体作基因分型，其中男166名，女158名，患病同胞对81个162例。采用受累同胞对法对分型资料进行非参数连锁分析。结果324人的两点、多点非参数分析最大LOD值均位于D16s407，分别为2．643(P=0．004)，2．504(P=0．005)，均大于2．2。结论NR2A基因微卫星标志与精神分裂症存在提示性连锁关系，NR2A基因可能为精神分裂症的易感基因之一。     

精神分裂症同胞家系的6号染色体基因组扫描研究

目的：通过对6号染色体进行候选区域的基因组扫描，探索精神分裂症的遗传易感基因。方法：以分布于6号染色体的28个微卫星标记在137个精神分裂症同胞家系样本中进行候选区域的基因扫描，采用受累同胞对分析方法，结合诊断分类，量表及必要的临床资料。通过GENEHUNTER ，MAPMAKER／SIBS等软件系统进行质量性状及数量性状的非参数连锁分析。结果：结合诊断分类的质量性状连锁分析未发现阳性结果。结合阳性和阴性症状量表（PANSS）的Haseman Elston数量性状连锁分析，结合PANSS－P分析所得最大Lod值为1．39，位于D6S1960附近，结合PANSS－G和PANSS－N所得最大Lod值分别为2．50和1．56，位于D6S291附近，变异因素数量性状分析与Haseman-Elason分析结果一致，即在相应的数量性状分析中，在D6S1960和D6S291附近，位点本身的遗传效应有明显作用的趋势。结论：6号染色体短臂可能存在精神分裂症的易感基因。     

中国汉族瘢痕疙瘩家系易感基因位点的定位分析

背景：转化生长因子β是目前与瘢痕关系最为密切的细胞因子，而SMAD蛋白介导的信号通路是转化生长因子β下游信号传递的主要途径。人SMAD蛋白基因在15q22.31-q23及18q21.1染色体区域。实验假定Smad基因为选择的瘢痕疙瘩家系易感基因位点。 目的：定位中国汉族瘢痕疙瘩家系的易感基因位点。 设计、时间及地点：两个家系、大样本的微卫星扫描连锁分析实验，于2007-02/06在上海基康公司实验室完成。 材料：选择6个国内不同地区的瘢痕疙瘩家系2个4代发病的NM、LN家系中32位和19位成员，严格遵照赫尔辛基宣言规定的准则采集血样和病理组织标本。 方法：采集2个家系51名成员的外周静脉血样，提取基因组DNA；选取位于15q22.31-q23及18q21.1染色体区域的7个微卫星标记位点D15S108 、D15S216、D15S534、D18S363、D18S460、D18S467、D18S846，对这些微卫星位点进行聚合酶链反应扩增，产物片断基因分型，再进行连锁分析。 主要观察指标：NM和LN瘢痕疙瘩家系外显率为90%时各位点LOD值。 结果：NM、LN两个瘢痕疙瘩家系在外显率分别为90%条件下，重组率θ=0~0.5时，这些微卫星标记的两点LOD值绝大部分都小于1，排除连锁关系存在。 结论：分析结果发现中国汉族瘢痕疙瘩家系易感基因位点不在染色体15q22.31-q23及18q21.1区域。     

双相障碍高发家系候选染色体区域的连锁分析

目的 探索定位双相障碍易感基因.方法 采集7个双相障碍高发家系,共90例家系成员,患者27例.选择6个染色体区域中的30个微卫星标记初步扫描,初步扫描结果阳性的区域选取12个微卫星标记精细扫描.GENEHUNTER2.1软件行连锁分析.结果 初步扫描D21S263、D21S1252和D22S423位点nonparametric logarithm of odds(NPL)值分别为1.64、1.41和1.40.精细扫描D21S262位点和D21S1920位点家系成员法和同胞对法计算NPL值分别为1.44、1.52、1.54和1.89.结论 21q22.11-13和22q13.1可能存在双相障碍的易感基因.     

常染色体显性遗传腓骨肌萎缩症一家系致病基因分析

目的 定位分析一常染色体显性遗传腓骨肌萎缩症家系的致病基因.方法 依据家系图、临床表现、神经肌肉电生理学及实验室检查结果,明确诊断一常染色体显性遗传腓骨肌萎缩症家系.采用16个基因位点的37个短串联重复序列(STR)标记方法进行连锁分析,以覆盖目前已经发现的20种常染色体显性遗传腓骨肌萎缩症亚型的16个致病基因位点.结果 所选择的37个STR标记均发生扩增反应,每一基因位点均呈现多态性.受检腓骨肌萎缩症家系呈常染色体显性遗传,其中3例患者在17p11.2-p12、1q22、16p12.3-p13.1、10q21.1、1p36.2、3q21、12q23、7p15、8p21、7q11-q21、12q12-q13、8q13-q21、12q24.3、10q24、19p12-p13及1p34-p35共16个基因位点的单倍体型均不存在等位基因共享,且家系所有成员致病基因均与16个已知常染色体显性遗传腓骨肌萎缩症致病基因位点不连锁.结论 研究过程中每一基因位点所用STR标记为2～3个,基本可以排除染色体互换,常染色体显性遗传腓骨肌萎缩症家系诊断依据充分;根据欧洲神经肌肉病中心制汀的确诊标准,可排除为已知类型的常染色体显性遗传腓骨肌萎缩症家系.推测为一新型腓骨肌萎缩症致病基因所引起的常染色体显性遗传腓骨肌萎缩症家系.     

NMDA受体NR1亚单位基因与精神分裂症的连锁分析

目的了解N-甲基-D-天冬氨酸(NMDA)受体NR1亚单位基因与精神分裂症的连锁关系。方法选取NR1亚单位基因所在区域的2个微卫星标记D9s1838和D9s1826,对94个符合美国精神障碍诊断与统计手册第4版精神分裂症诊断标准(DSM-Ⅳ)的中国汉族精神分裂症受累同胞对及家系成员共376个个体作基因分型,其中男性194名,女性182名。采用美国国立精神卫生研究所(NIMH)制订的《遗传研究诊断问卷》(DIGS),对家系成员躯体和精神状况进行评定;采用NIMH制订的《遗传研究家族问卷》(FIGS)了解家系结构。选用GENEHUNTER2.1软件对分型资料进行非参数连锁分析。结果两点、多点非参数分析最大LOD值均位于D9s1826,分别为1.70(P=0.050),2.08(P=0.015),两者均大于验证性连锁阈值1.2。结论NR1基因区域微卫星标记与精神分裂症存在验证性连锁关系,提示NR1基因可能为精神分裂症的易感基因之一。     

Evidence for a putative bipolar disorder locus on 2p13-16 and other potential loci on 4q31, 7q34, 8q13, 9q31, 10q21-24, 13q32, 14q21 and 17q11-12

Bipolar disorder (BP) is a severe and common psychiatric disorder characterized by extreme mood swings. Family, twin and adoption studies strongly support a genetic component. The mode of inheritance is complex and likely involves multiple, as yet unidentified genes. To identify susceptibility loci, we conducted a genome-wide scan with 343 microsatellite markers in one of the largest, well-characterized pedigree samples assembled to date (373 individuals in 40 pedigrees). To increase power to detect linkage, scan statistics were used to examine the logarithm of odds (lod) scores based on evidence at adjacent chromosomal loci. This analysis yielded significant evidence of linkage (genome-wide P&<0.05) for markers on 2p13-16. Standard linkage analysis was also supportive of linkage to 2p13-16 (lod=3.20), and identified several other interesting regions: 4q31 (lod=3.16), 7q34 (lod=2.78), 8q13 (lod=2.06), 9q31 (lod=2.07), 10q24 (lod=2.79), 13q32 (lod=2.2), 14q21 (lod=2.36) and 17q11-12 (lod=2.75). In this systematic, large-scale study, we identified novel putative loci for BP (on 2p13-16, 8q13 and 14q21) and found support for previously proposed loci (on 4q31, 7q34, 9q31, 10q21-24, 13q32 and 17q11-12). Two of the regions implicated in our study, 2p13-14 and 13q32, have also been linked to schizophrenia, suggesting that the two disorders may have susceptibility genes in common.     

Susceptibility loci for bipolar disorder: overlap with inherited vulnerability to schizophrenia.

Genetic epidemiological studies reveal that relatives of bipolar probands are at increased risk for recurrent unipolar, bipolar, and schizoaffective disorders, whereas relatives of probands with schizophrenia are at increased risk for schizophrenia, schizoaffective, and recurrent unipolar disorders. The overlap in familial risk may reflect shared genetic susceptibility. Recent genetic linkage studies have defined confirmed bipolar susceptibility loci for multiple regions of the human genome, including 4p16, 12q24, 18p11.2, 18q22, 21q21, 22q11-13, and Xq26. Studies of schizophrenia kindreds have yielded robust evidence for susceptibility at 18p11.2 and 22q11-13, both of which are implicated in susceptibility to bipolar disorder. Similarly, confirmed schizophrenia vulnerability loci have been mapped, too, for 6p24, 8p, and 13q32. Strong statistical evidence for a 13q32 bipolar susceptibility locus has been reported. Thus, both family and molecular studies of these disorders suggest shared genetic susceptibility. These two groups of disorders may not be as distinct as current nosology suggests.     

A novel locus for inherited myoclonus-dystonia on 18p11

OBJECTIVE: Inherited myoclonus-dystonia (IMD) is a new term for an autosomal dominant disorder characterized by myoclonus and dystonia. Recently, IMD was linked to a region on chromosome 11q23 with two different mutations identified in the D2 dopamine receptor gene and linked to chromosome 7q with five different loss-of-function mutations identified in the epsilon-sarcoglycan gene. METHODS: These two regions and genes were excluded in a large Canadian family with IMD in whom 13 individuals are affected. A 25-cM genome scan of this large family with 32 individuals was performed. RESULTS: Two-point linkage analysis revealed a maximum lod score of 3.5 (recombination fraction 0.00; affected only) for the microsatellite marker GATA185C06-18 and a multipoint lod score of 3.9 across the 18p11 region. Haplotype analysis demonstrates that all the affected individuals shared a common haplotype between markers D18S1132 and D18S843 that defines the disease gene within a span of 16.9 cM. CONCLUSIONS: These findings indicate that a novel IMD gene exists on chromosome 18p11.     

A genome-wide scan for linkage to chromosomal regions in 382 sibling pairs with schizophrenia or schizoaffective disorder

OBJECTIVE: Some genome-wide scans and association studies for schizophrenia susceptibility genes have yielded significant positive findings, but there is disagreement between studies on their locations, and no mutation has yet been found in any gene. Since schizophrenia is a complex disorder, a study with sufficient power to detect a locus with a small or moderate gene effect is necessary. METHOD: In a genome-wide scan of 382 sibling pairs with a diagnosis of schizophrenia or schizoaffective disorder, 396 highly polymorphic markers spaced approximately 10 centimorgans apart throughout the genome were genotyped in all individuals. Multipoint nonparametric linkage analysis was performed to evaluate regions of the genome demonstrating increased allele sharing, as measured by a lod score. RESULTS: Two regions with multipoint maximum lod scores suggesting linkage were found. The highest lod scores occurred on chromosome 10p15-p13 (peak lod score of 3.60 at marker D10S189) and the centromeric region of chromosome 2 (peak lod score of 2.99 at marker D2S139). In addition, a maximum lod score of 2.00 was observed with marker D22S283 on chromosome 22q12, which showed evidence of an imprinting effect, whereby an excess sharing of maternal, but not paternal, alleles was present. No evidence of linkage was obtained at several locations identified in previous studies, including chromosomes 1q, 4p, 5p-q, 6p, 8p, 13q, 15p, and 18p. CONCLUSIONS: The findings of this large genome-wide scan emphasize the weakness and fragility of linkage reports on schizophrenia. No linkage appears to be consistently replicable across large studies. Thus, it has to be questioned whether the genetic contribution to this disorder is detectable by these strategies and the possibility raised that it may be epigenetic, i.e., related to gene expression rather than sequence variation. Nevertheless, the positive findings on chromosome 2, 10, and 22 should be pursued further.     

Linkage analysis of psychosis in bipolar pedigrees suggests novel putative loci for bipolar disorder and shared susceptibility with schizophrenia

The low-to-moderate resolution of linkage analysis in complex traits has underscored the need to identify disease phenotypes with presumed genetic homogeneity. Bipolar disorder (BP) accompanied by psychosis (psychotic BP) may be one such phenotype. We previously reported a genome-wide screen in a large bipolar pedigree sample. In this follow-up study, we reclassified the disease phenotype based on the presence or absence of psychotic features and subgrouped pedigrees according to familial load of psychosis. Evidence for significant linkage to psychotic BP (genome-wide P<0.05) was obtained on chromosomes 9q31 (lod=3.55) and 8p21 (lod=3.46). Several other sites were supportive of linkage, including 5q33 (lod=1.78), 6q21 (lod=1.81), 8p12 (lod=2.06), 8q24 (lod=2.01), 13q32 (lod=1.96), 15q26 (lod=1.96), 17p12 (lod=2.42), 18q21 (lod=2.4), and 20q13 (lod=1.98). For most loci, the highest lod scores, including those with genome-wide significance (at 9q31 and 8p21), occurred in the subgroup of families with the largest concentration of psychotic individuals (> or =3 in a family). Interestingly, all regions but six--5q33, 6q21, 8p21, 8q24, 13q32 and 18q21--appear to be novel; namely, they did not show notable linkage to BP in other genome scans, which did not employ psychosis for disease classification. Also of interest is possible overlap with schizophrenia, another major psychotic disorder: seven of the regions presumed linked in this study--5q, 6q, 8p, 13q, 15q, 17p, and 18q--are also implicated in schizophrenia, as are 2p13 and 10q26, which showed more modest support for linkage. Our results suggest that BP in conjunction with psychosis is a potentially useful phenotype that may: (1) expedite the detection of susceptibility loci for BP and (2) cast light on the genetic relationship between BP and schizophrenia.     

Genetic heterogeneity in schizophrenia: stratification of genome scan data using co-segregating related phenotypes

Despite considerable effort to identify susceptibility loci for schizophrenia, none have been localized. Multiple genome scans and collaborative efforts have shown evidence for linkage to regions on chromosomes 1q, 5q, 6q, 8p, 13q, 10p and 22q.(1-9) Heterogeneity is likely. We previously mapped schizophrenia susceptibility loci (SSL) to chromosomes 13q32 (P = 0.00002) and 8p21-22 (P= 0.0001) using 54 multiplex pedigrees and suggested linkage heterogeneity. We have now stratified these families based on co-segregating phenotypes in non-schizophrenic first degree relatives (schizophrenia spectrum personality disorders (SSPD); psychotic affective disorders (PAD)). Genome scans were conducted for these phenotypic subgroups of families and broadened affected phenotypes were tested. The SSPD group provided its strongest genome-wide linkage support for the chromosome 8p21 region (D8S1771) using either narrow (non-parametric lod (NPL) P= 0.000002) or broadened phenotypes (NPL P = 0.0000008) and a new region of interest on 1p was identified (P = 0.006). For PAD families, the peak NPL in the genome scan occurred on chromosome 3p26-p24 (P = 0.008). The identification of multiple susceptibility loci for schizophrenia may be enhanced by stratification of families using psychiatric diagnoses of the non-schizophrenic relatives.     

Genome-wide scans of three independent sets of 90 Irish multiplex schizophrenia families and follow-up of selected regions in all families provides evidence for multiple susceptibility genes

From our linkage study of Irish families with a high density of schizophrenia, we have previously reported evidence for susceptibility genes in regions 5q21-31, 6p24-21, 8p22-21, and 10p15-p11. In this report, we describe the cumulative results from independent genome scans of three a priori random subsets of 90 families each, and from multipoint analysis of all 270 families in ten regions. Of these ten regions, three (13q32, 18p11-q11, and 18q22-23) did not generate scores above the empirical baseline pairwise scan results, and one (6q13-26) generated a weak signal. Six other regions produced more positive pairwise and multipoint results. They showed the following maximum multipoint H-LOD (heterogeneity LOD) and NPL scores: 2p14-13: 0.89 (P = 0.06) and 2.08 (P = 0.02), 4q24-32: 1.84 (P = 0.007) and 1.67 (P = 0.03), 5q21-31: 2.88 (P= 0.0007), and 2.65 (P = 0.002), 6p25-24: 2.13 (P = 0.005) and 3.59 (P = 0.0005), 6p23: 2.42 (P = 0.001) and 3.07 (P = 0.001), 8p22-21: 1.57 (P = 0.01) and 2.56 (P = 0.005), 10p15-11: 2.04 (P = 0.005) and 1.78 (P = 0.03). The degree of 'internal replication' across subsets differed, with 5q, 6p, and 8p being most consistent and 2p and 10p being least consistent. On 6p, the data suggested the presence of two susceptibility genes, in 6p25-24 and 6p23-22. Very few families were positive on more than one region, and little correlation between regions was evident, suggesting substantial locus heterogeneity. The levels of statistical significance were modest, as expected from loci contributing to complex traits. However, our internal replications, when considered along with the positive results obtained in multiple other samples, suggests that most of these six regions are likely to contain genes that influence liability to schizophrenia.     

Linkage of a bipolar disorder susceptibility locus to human chromosome 13q32 in a new pedigree series

Bipolar (BP) disorder or manic depressive illness is a major psychiatric disorder for which numerous family, twin and adoption studies support a substantial genetic contribution. Recently, we reported the results of a genome-wide search for BP disorder susceptibility loci in 20 pedigrees. Suggestive evidence for linkage was found in this study at three markers on 13q, representing possibly two peaks separated by 18 cM. We have now collected a second set of 32 pedigrees segregating BP disorder and have tested for evidence of linkage to markers on human chromosome 13q. In this sample, we have replicated the linkage result in 13q32 at D13S154 (lod=2.29), the more proximal of the two original peaks. When all 52 pedigrees were combined, the multipoint maximum lod score peaked approximately 7 cM proximal to D13S154 (lod=3.40), with a second peak occurring between D13S225 and D13S796 (lod=2.58). There have been several other reports of significant linkage to both BP disorder and schizophrenia in this region of chromosome 13. These pedigrees provide additional evidence for at least one locus for BP disorder in 13q32, and are consistent with other reports of a possible genetic overlap between these disorders.     

Familial hemiplegic migraine: clinical features and probable linkage to chromosome 1 in an Italian family

We describe an Italian family with familial hemiplegic migraine (FHM), subtle cerebellar signs and probable linkage to chromosome 1. FHM is genetically heterogeneous; in about 50% of families it is caused by mutations within the CACNA1A gene on chromosome 19. Linkage to 1q31 and 1g21–23 has also been established. Other families do not link either to chromosome 19 or 1. Chromosome 19-linked FHM may display nystagmus and cerebellar ataxia. Affected family members were neurologically examined; linkage analysis was performed with markers for chromosomes 19p13, 1q21–23, and 1q32. Five family members had hemiplegic migraine, and 3 displayed additional cerebellar signs (scanning speech and nystagmus). In 1 patient, episodes of hemiplegic migraine triggered by mild head trauma. Epilepsy and mental retardation were also found in 1 affected relative each. Lod scores for linkage to 19p13 were negative, while the maximum two-point lod score was 1.81 to 1q21–23. This family with FHM and associated subtle cerebellar signs, epilepsy and mental retardation showed probable linkage to 1q21–23. Received: 27 December 2001 / Accepted in revised form: 27 February 2002     

Shared and specific susceptibility loci for schizophrenia and bipolar disorder: a dense genome scan in Eastern Quebec families

The goal of this study was to identify susceptibility loci shared by schizophrenia (SZ) and bipolar disorder (BP), or specific to each. To this end, we performed a dense genome scan in a first sample of 21 multigenerational families of Eastern Quebec affected by SZ, BP or both (N=480 family members). This probably constitutes the first genome scan of SZ and BP that used the same ascertainment, statistical and molecular methods for the concurrent study of the two disorders. We genotyped 607 microsatellite markers of which 350 were spaced by 10 cM and 257 others were follow-up markers in positive regions at the 10 cM scan. Lander and Kruglyak thresholds were conservatively adjusted for multiple testings. We maximized the lod scores (mod score) over eight combinations (2 phenotype severity levels x 2 models of transmission x 2 analyses, affected/unaffected vs affected-only). We observed five genomewide significant linkages with mod score >4.0: three for BP (15q11.1, 16p12.3, 18q12-q21) and two for the shared phenotype, that is, the common locus (CL) phenotype (15q26,18q12-q21). Nine mod scores exceeded the suggestive threshold of 2.6: three for BP (3q21, 10p13, 12q23), three for SZ (6p22, 13q13, 18q21) and three for the CL phenotype (2q12.3, 13q14, 16p13). Mod scores >1.9 might represent confirmatory linkages of formerly reported genomewide significant findings such as our finding in 6p22.3 for SZ. Several regions appeared to be shared by SZ and BP. One linkage signal (15q26) appeared novel, whereas others overlapped formerly reported susceptibility regions. Despite the methodological limitations we raised, our data support the following trends: (i) results from several genome scans of SZ and BP in different populations tend to converge in specific genomic regions and (ii) some of these susceptibility regions may be shared by SZ and BP, whereas others may be specific to each. The present results support the relevance of investigating concurrently SZ and BP within the same study and have implications for the modelling of genetic effects.