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. 2005 Oct 12;77(6):937–944. doi: 10.1086/498122

Genomewide High-Density SNP Linkage Analysis of 236 Japanese Families Supports the Existence of Schizophrenia Susceptibility Loci on Chromosomes 1p, 14q, and 20p

Japanese Schizophrenia Sib-Pair Linkage Group, Tadao Arinami *, Tsuyuka Ohtsuki *, Hiroki Ishiguro *, Hiroshi Ujike *, Yuji Tanaka, Yukitaka Morita, Mari Mineta *,†, Masashi Takeichi, Shigeto Yamada *, Akira Imamura *, Koichi Ohara *, Haruo Shibuya *, Kenshiro Ohara, Yasuo Suzuki, Tatsuyuki Muratake *, Naoshi Kaneko, Toshiyuki Someya *, Toshiya Inada *, Takeo Yoshikawa *, Tomoko Toyota *, Kazuo Yamada *, Takuya Kojima *, Sakae Takahashi *, Ohmori Osamu *, Takahiro Shinkai *, Michiko Nakamura *, Hiroshi Fukuzako *, Tomo Hashiguchi, Shin-ich Niwa *, Takuya Ueno, Hirokazu Tachikawa *, Takafumi Hori *, Takashi Asada *, Shinichiro Nanko *, Hiroshi Kunugi *, Ryota Hashimoto *, Norio Ozaki *, Nakao Iwata *, Mutsuo Harano *, Heii Arai, Tohru Ohnuma *, Ichiro Kusumi *, Tsukasa Koyama, Hiroshi Yoneda *, Yasuyuki Fukumaki *, Hiroki Shibata, Sunao Kaneko *, Hisashi Higuchi, Norio Yasui-Furukori, Yohtaro Numachi *, Masanari Itokawa *, Yuji Okazaki *,‡
PMCID: PMC1285184  PMID: 16380906

Abstract

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG) is a multisite collaborative study group that was organized to create a national resource for affected sib pair (ASP) studies of schizophrenia in Japan. We used a high-density single-nucleotide–polymorphism (SNP) genotyping assay, the Illumina BeadArray linkage mapping panel (version 4) comprising 5,861 SNPs, to perform a genomewide linkage analysis of JSSLG samples comprising 236 Japanese families with 268 nonindependent ASPs with schizophrenia. All subjects were Japanese. Among these families, 122 families comprised the same subjects analyzed with short tandem repeat markers. All the probands and their siblings, with the exception of seven siblings with schizoaffective disorder, had schizophrenia. After excluding SNPs with high linkage disequilibrium, we found significant evidence of linkage of schizophrenia to chromosome 1p21.2-1p13.2 (LOD=3.39) and suggestive evidence of linkage to 14q11.2 (LOD=2.87), 14q11.2-q13.2 (LOD=2.33), and 20p12.1-p11.2 (LOD=2.33). Although linkage to these regions has received little attention, these regions are included in or partially overlap the 10 regions reported by Lewis et al. that passed the two aggregate criteria of a meta-analysis. Results of the present study—which, to our knowledge, is the first genomewide analysis of schizophrenia in ASPs of a single Asian ethnicity that is comparable to the analyses done of ASPs of European descent—indicate the existence of schizophrenia susceptibility loci that are common to different ethnic groups but that likely have different ethnicity-specific effects.

Introduction

Schizophrenia (MIM 181500) is a common disorder, with a lifetime morbidity risk of 1%. A large number of family, twin, and adoption studies have revealed that individual differences in susceptibility are predominantly genetic, with a heritability of 0.70–0.85 and a 10-fold increased risk in siblings of probands (Levinson and Mowry 2000). More than 20 genome scans for susceptibility loci for schizophrenia have been completed, and evidence satisfying genomewide significance levels for linkage to schizophrenia was obtained for chromosome regions 6p24-p22 (MIM 600511) (Straub et al. 1995), 1q21-q22 (MIM 604906) (Brzustowicz et al. 2000), 13q32-q34 (MIM 603176) (Blouin et al. 1998), 10p14 (DeLisi et al. 2002b), and 10q25.3-q26.3 (Williams et al. 2003). Linkage for other regions—including 8p22-p21 (MIM 603013) (Kendler et al. 1996; Blouin et al. 1998), 6q21-q25 (MIM 603175) (Cao et al. 1997; Lindholm et al. 2001), 22q11-q12 (MIM 600850) (Pulver et al. 1994; Schizophrenia Linkage Collaborative Group for Chromosomes 3 and 8 1996), and 5q21-q33 (MIM 181510) (Bassett et al. 1988; Paunio et al. 2001)—has been reported multiple times. However, none of the above-named regions has been identified consistently in a majority of the genome scans. It is possible that loci with small populationwide effects hinder confirmation of linkage because replication of linkage data requires a larger sample population than the original data set (Suarez et al. 1994) and because the samples for most genome scans of schizophrenia have been small, typically 20–100 families.

Some problems of power and replication can be addressed by meta-analysis. Lewis and colleagues (2003) used the rank-based genome-scan meta-analysis (GSMA) method to analyze 20 complete genome scans for susceptibility loci for schizophrenia. In GSMA, the autosomes were divided into 30-cM bins, and the evidence of linkage in each study was rank ordered across bins with and without weights for sample size. The average ranks across studies were evaluated for statistically significant evidence of linkage in several ways. Lewis et al. (2003) concluded that schizophrenia loci are highly likely to be present in one or more of the following regions: 1p13.3-q23.3, 2p12-q23.3, 3p25.3-p22.1, 5q23.2-q34, 6pter-p21.1, 8p22-p21.1, 11q22.3-q24.1, 14pter-q13.1, 20p12.3-p11, and 22pter-q12.3, all of which met two aggregate criteria for linkage. Another meta-analysis found significant results only for chromosomes 8p, 13q, and 22q (Badner and Gershon 2002). However, meta-analysis has limitations (Levinson et al. 2003). One is that meta-analysis methods may not distinguish several weakly linked loci in the same region. This issue can be addressed by pooling the raw genotyping data for meta-analysis. Analysis of a multicenter sample of 779 pedigrees did not yield significant evidence of linkage of 22q to schizophrenia (Mowry et al. 2004); however, those authors suggested that collaborative pooling of data sets was limited by intersite differences in sampling frames, population ethnicity, and genotyping methods.

The largest genomewide linkage findings to date were reported by DeLisi and colleagues (2002b), who studied 294 families with 382 nonindependent affected sib pairs (ASPs) with schizophrenia or schizoaffective disorder from the United States, the United Kingdom, Italy, Chile, and Belgium. Williams and colleagues (2003) described linkage findings in 272 families with 353 nonindependent ASPs from the United Kingdom, Sweden, and the United States. Among these ASPs, 287 nonindependent ASPs in 231 families received a diagnosis of schizophrenia or schizoaffective disorder. Straub and colleagues (2002) described linkage findings in 270 families with 261 nonindependent ASPs with schizophrenia or poor-outcome schizoaffective disorder from Ireland and Northern Ireland. The Irish families were ethnically homogeneous, and most of the pedigrees in the other two studies were of European origin. The narrow ethnic distributions of these sample populations could have influenced the results, because an ethnically diverse study population has increased potential for variation, which could result in heterogeneity at certain susceptibility loci. A recent study found ethnic heterogeneity between European and East Asian populations in allelic association of the 102T/C polymorphism of the HTR2A gene (MIM 182135) with schizophrenia (Abdolmaleky et al. 2004). This type of heterogeneity compounds the recognized difficulty in characterizing genetically complex diseases for which the magnitude of the effect of any one locus is unknown.

The Japanese Schizophrenia Sib-Pair Linkage Group (JSSLG), a multisite collaborative study group, was established in 1997 as a national resource for genetic studies of schizophrenia. An initial genomewide linkage study was performed with 417 STR markers in 130 families; however, no loci with significant linkage to schizophrenia were detected (JSSLG 2003). We recruited additional families to participate in the JSSLG study and analyzed 236 families with 268 nonindependent ASPs with a high-density SNP linkage mapping set. High-density SNP linkage mapping systems provide significantly improved levels of information extraction with extremely high accuracy, particularly when founder genotypes are unavailable (Sawcer et al. 2004).

Material and Methods

Subjects

Linkage of genetic loci to schizophrenia was analyzed in Japanese families with at least two available siblings who had received the diagnosis of schizophrenia or schizoaffective disorder. A total of 236 families with 602 individuals were recruited at 24 centers across Japan (table 1). Of these, 122 families with 315 individuals comprised the same subjects analyzed by STR markers that we reported elsewhere (JSSLG 2003). Each family member received the diagnosis on the basis of the DSM-IV structured clinical interview. Each face-to-face interview was conducted by two experienced interviewers. In addition to direct interviews, all available medical records and information from relatives and hospital staff were considered. Inclusion criteria for this collaborative sample recruitment were DSM-IV-defined schizophrenia for probands and schizophrenia or schizoaffective disorder for affected siblings. Seven siblings with schizoaffective disorder were included. All participants and their parents were of Japanese descent. The study protocol was approved by the ethics committee of each institution, and written informed consent was obtained from all subjects.

Table 1.

JSSLG Subjects

No. of JSSLG Families
Both Parentsb
 One Parentb
 No Parentb
Centera No. of Families 2Affected Sibs 3Affected Sibs 2Affected Sibs 3Affected Sibs 2Affected Sibs 3Affected Sibs
Hakkaido University 2 0 0 0 0 1 1
Hirosaki University 1 0 0 0 0 0 1
Minami Hanamaki National Hospital 18 5 0 8 0 5 0
Tohoku University 1 0 0 0 0 1 0
Fukushima Medical University 4 0 0 2 0 2 0
Niigata University 19 3 0 2 0 14 0
University of Tsukuba 16 0 0 3 2 10 1
Teikyo University Ichihara Hospital 23 0 0 2 0 21 0
RIKEN Brain Science Institute 7 5 0 2 0 0 0
Juntendo University 3 2 0 1 0 0 0
Toho University 10 0 0 0 0 10 0
Tokyo Institute of Psychiatry 1 0 0 0 0 0 1
Nihon University 11 1 1 0 0 9 0
Teikyo University 4 0 0 2 0 2 0
National Center of Neurology and Psychiatry 5 0 0 0 0 5 0
Fujita Health University 7 0 0 0 0 7 0
Osaka Medical College 4 0 0 0 0 4 0
Okayama University 33 0 0 2 0 27 4
University of Occupational and Environmental Health 10 1 0 0 0 9 0
Kyushu University 2 0 0 0 0 2 0
Kurume University 7 0 0 0 0 7 0
Saga Medical School 22 5 1 5 1 10 0
Nagasaki University 19 7 0 7 1 3 1
Kagoshima University  7
 0
 1
 1
 0
  5
 0
 Total 236 29 3 37 4 154 9
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a

In order of location from north to south.

b

Available for genotyping.

Genotyping

The Illumina SNP-based Linkage Panel IV was used for genotyping. The panel includes 5,861 SNP markers distributed evenly across the genome. The average and median intervals between markers were 503 kb (0.64 cM) and 301 kb (0.35 cM), respectively. The largest interval between successfully genotyped markers was 4.9 Mb (8.8 cM) on chromosome Xp21. The Illumina markers were typed with the Illumina BeadStation 500G, in accordance with the manufacturer’s standard recommendations.

Statistical Analysis

Multipoint linkage analysis was performed along the entire length of each chromosome with the MERLIN program (Center of Statistical Genetics) developed by Abecasis et al. (2002). Both the nonparametric linkage (NPL) Z score and nonparametric LOD score, calculated with the Kong and Cox (1997) linear model, were extracted from the MERLIN runs and were used to generate graphic plots of the whole-genome scan results. Because linkage disequilibrium (LD) between closely spaced SNP markers can falsely inflate linkage statistics, we used the SNPLINK program (Webb et al. 2005; Institute of Cancer Research), which removes LD from the marker sets in an automated fashion. Because the program considers LD between pairs of adjacent SNPs, the possibility of high LD between nonadjacent SNPs but low LD between adjacent SNPs, such as a situation in which there was high LD between SNPs 41 and 43 and low LD between SNPs 41 and 42 and between SNPs 42 and 43, was examined with the Haploview program. Because no empirical justification to remove LD by any criteria has been published, we tested the significant and suggestive regions, using a range of criteria from r2=0.4, and gradually decreased the thresholds to r2=0.05. The linkage panel includes 28 SNPs from the pseudoautosomal regions of the X chromosome (20 from the short arm; 8 from the long arm). Because no currently available multipoint linkage program can integrate data from X-linked and pseudoautosomal markers in a single analysis, each pseudoautosomal region was analyzed separately, as though it were an independent autosomal chromosome. The results of these analyses were then combined with those from the standard X-linked markers. Empirical P values were calculated for the NPL Z and LOD scores via simulation. MERLIN was used to generate 50,000 replicates of families identical to those in our sample. Markers with similar allele frequencies were also generated under the assumption of no linkage. Linkage analyses were then performed on these unlinked replicates, and peaks of NPL Z and LOD scores separated by at least 30 cM on each chromosome were recorded for each simulation. Simulation studies of our genome scan suggested that, on average, an NPL Z of 2.87 and a LOD of 2.06 per genome scan would have been expected, whereas an NPL Z of 3.48 and a LOD of 3.07 would have been expected to occur only once in every 20 genome scans in the absence of linkage. Therefore, these values correspond to “suggestive” and “significant” thresholds for genomewide significance, as defined by Lander and Kruglyak (1995). The GeneFinder program (Liang et al. 2001; Chiu et al. 2002; Glidden et al. 2003) was used to obtain 95% CIs for the locations of linked loci. The information content of the genotypes was estimated by MERLIN, with use of entropy information described by Kruglyak et al. (1996). Simulations suggested that our study had a power of >0.99, 0.79, 0.38, and 0.05 to detect a susceptibility locus of λs=3, 2, 1.5, and 1.25 for schizophrenia, with a genomewide significance of P=.05.

Results

Among our Japanese family members, we observed an average minor-allele frequency of 0.29 and a mean heterozygosity of 0.37. These values were identical to those in Asian populations in the Illumina Linkage IV Panel. In our Japanese population, 125 SNPs were not polymorphic. The call rate (percentage of successful genotype calls among subjects) was used as a measure of quality. The average call rate was 98.5%, and we excluded 10 SNPs with call rates of <90%. The rate of Mendelian inconsistency or impossible recombination identified by the MERLIN program was 0.027% in the families with parents available for genotyping. Because the low heterozygosity of SNPs means that only 37% of genotyping errors will appear as Mendelian inconsistencies (Abecasis et al. 2002), the approximate genotyping error rate was estimated to be 0.073%.

Results of the linkage analysis are presented in figure 1. One region, 1p21.1, showed genomewide significance (P<.05) on the basis of simulation studies (LOD=3.39; NPL Z=3.96) with a 95% CI of 102.0–111.9 Mb (National Center for Biotechnology Information [NCBI] build 35). We also obtained suggestive evidence of linkage to chromosome 14q11.2 (LOD=2.87; NPL Z=3.14), with a 95% CI of 19.4–34.9 Mb; chromosome 14q12 (LOD=2.33; NPL Z=2.95), with a 95% CI of 19.4–34.9 Mb; and chromosome 20p11.2 (LOD=2.33; NPL Z=3.10), with a 95% CI of 16.0–33.2 Mb (table 2). Notable results were also obtained for chromosomes 4q24 (LOD=1.44; NPL Z=2.32), 4q31.3 (LOD=1.44; NPL Z=2.42), 12q24.3 (LOD=1.91; NPL Z=2.67), and 19p13.3 (LOD=1.49; NPL Z=2.32).

Figure 1.

Figure 1

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Multipoint nonparametric LOD score (Kong and Cox 1997) of genomewide scan for JSSLG ASPs with schizophrenia

Table 2.

Chromosome Regions with Genomewide Significant and Suggestive Linkage to Schizophrenia in 268 Nonindependent JSSLG ASPs

Peak SNP ChromosomeRegion Distancefrom pterMarker(cM) Positiona(Mb) NPL Z (P) LODb (P) 95% CI SNP Regiona 95% CIPositiona(Mb) 95% CIChromosomeRegion
rs2048839  1p21.1 126.18 105.7 3.96 (.00004) 3.39 (.00004) rs1445225–rs575208 102.0–111.9 1p21.2-p13.2
rs1319956  14q11.2 .00 19.4 3.14 (.0009) 2.87 (.0001) rs1319956–rs8904 19.4–34.9 14q11.2-q13.2
rs7149108  14q12 31.14 32.0 2.95 (.002) 2.33 (.0005) rs1319956–rs8904 19.4–34.9 14q11.2-q13.2
rs7988  20p11.2 53.08 23.3 3.10 (.001) 2.33 (.0005) rs775133–rs663550 16.0–33.2 20p12.1-q11.2
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a

NCBI build 35.

b

Calculated with the Kong and Cox (1997) linear model.

Among 5,736 SNPs, 22 pairs of nonadjacent SNPs were in LD with r2>0.05 but no adjacent SNPs were in LD with r2<0.05. However, no such pairs were located in the significant and suggestive regions. The LOD scores were not changed by decreasing the thresholds to remove LD in the SNPLINK program, because pairs of adjacent SNPs showed high LD (r2>0.4) or no or very low LD (r2<0.01) in these regions.

Discussion

In our previous study of 130 families (JSSLG 2003), we did not observe any significant or suggestive evidence of linkage with schizophrenia. Of the 236 families examined in the present study, 122 had been analyzed previously. The present study revealed significant and suggestive evidence of linkage of specific chromosome regions to schizophrenia. The larger number of families and increased information extracted by the high-density SNP linkage system used in the present study may have contributed to the present results. The overall genetic linkage information content per 3-cM interval increased from 0.48 in our previous study (JSSLG 2003) to 0.72 in the present study. In addition to the increase in extractable information, high-throughput DNA typing technology is advantageous because it is accurate, fast, and requires little DNA. The genotyping error rate was ∼0.073% in the present study. Although error rates are rarely published—and when they are expressed, the terminology varies greatly—it is noteworthy that microsatellite error rates of 0.1%–12.7% per reaction have been reported (Brzustowicz et al. 1993; Ginot et al. 1996; Ghosh et al. 1997; Ewen et al. 2000; Sobel et al. 2002; Weeks et al. 2002). Abecasis et al. (2001) reported that error rates of just 1% can reduce observed LOD scores by as much as 50%.

Our strongest finding was significant evidence of linkage of schizophrenia to the region 1p21-p13. To our knowledge, studies of linkage to schizophrenia have not focused on linkage to this region. However, this region overlaps a telomeric part of bin 1.6, which showed evidence of linkage to schizophrenia in the meta-analysis reported by Lewis et al. (2003) (table 2). A small peak LOD score for this region was observed in a cohort in the Central Valley of Costa Rica (DeLisi et al. 2002a). An NPL score of 2.72 for region 1p21 was observed in seven families with schizophrenia or schizophrenia spectrum personality disorders (Pulver et al. 2000). The NTNG1 gene (MIM 608818) is located on 1p13.3 and may be a candidate gene for schizophrenia susceptibility. Association between specific haplotypes encompassing alternatively spliced exons of NTNG1 and schizophrenia was observed in a Japanese population (Aoki-Suzuki et al. 2005).

Suggestive evidence of linkage to 14q11.2-q13.2 was also obtained in the present study. One region with NPL scores >2.0 in Arab-Israeli families was 14q11.1-q11.2 (Lerer et al. 2003). Potential linkage of schizophrenia to 14q13 was reported for the Maryland epidemiologic sample comprising 44 families of European descent (NPL=2.57; P=.005) (Blouin et al. 1998). A mother and daughter who received the diagnoses of schizophrenia and schizophrenia comorbid with mild learning disability, respectively, possessed a balanced reciprocal translocation t(9,14)(q34.2;q13), and the NPAS3 gene (MIM 609430) on 14q13.1 (32.5–33.3 Mb) was disrupted (Kamnasaran et al. 2003; Pickard et al. 2005). The region of 14q11.2-q13.2 is included in bin 14.1, which showed evidence of linkage in the meta-analysis reported by Lewis et al. (2003) (table 2).

Suggestive evidence of linkage to 20p11.2 was also obtained in the present study. Linkage of 20p11 with bipolar disorders has been reported (Radhakrishna et al. 2001; McInnis et al. 2003). This region is included in bin 20.2, which showed evidence of linkage with schizophrenia in the meta-analysis reported by Lewis et al. (2003) (table 2).

In the present study, all of the regions that showed significant and suggestive evidence of linkage to schizophrenia are included in or partially overlap the 10 regions that passed the two aggregate criteria of a meta-analysis (Lewis et al. 2003), although these regions have not received much attention (Owen et al. 2004). Therefore, the presence of susceptibility loci for schizophrenia in both European and Asian populations in these regions is plausible, although these loci may have larger populationwide effects on schizophrenia in Asian populations than in European populations. Additional larger studies of Asian populations might validate the hypothesis (Hwu et al. 2005). In conclusion, the present JSSLG linkage study of Japanese families—which is one of the largest genomewide ASP analyses of a single ethnicity for schizophrenia to date and is comparable to genomewide ASP analyses of families of European descent with schizophrenia—supports the existence of schizophrenia susceptibility loci common to different ethnic groups but with possible ethnic-specific effects.

Acknowledgments

We thank Dr. Emiko Noguchi for technical assistance with the statistical procedures.

Author affiliations.—Department of Medical Genetics, Graduate School of Comprehensive Human Sciences (T. Arinami, T. Ohtsuki, and H.I.), and Department of Psychiatry, Institute of Clinical Medicine (H.T., T.H., and T. Asada), University of Tsukuba, Tsukuba, Japan; CREST, Japan Science and Technology Agency, Kawaguchi, Japan (T. Arinami, T. Ohtsuki, H.I., A.I., T.M., T.I., T.Y., T. Asada, N.O., Y.F., M.I., and Y.O.); Department of Neuropsychiatry, Okayama University, Graduate School of Medicine, Dentistry & Pharmaceutical Sciences, Okayama, Japan (H.U., Y.T., and Y.M.); Department of Psychiatry, Faculty of Medicine, Saga University, Saga, Japan (M.M., M.T., and S.Y.); Division of Neuropsychiatry, Department of Translational Medical Sciences, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki (A.I.); Clinical Research Institute, National Minami Hanamaki Hospital, Hanamaki, Japan (Koichi Ohara and H. Shibuya); Department of Psychiatry, Hamamatsu University School of Medicine, Hamamatsu, Japan (Koichi Ohara, Kensiro Ohara, and Y.S.); Department of Psychiatry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan (T.M., N.K., and T. Someya); Department of Psychiatry, Ichihara Hospital, Teikyo University School of Medicine Anesaki, Ichihara, Japan (T.I.); Laboratory for Molecular Psychiatry, RIKEN Brain Science Institute, Wako, Japan (T.Y., T.T., and K.Y.); Department of Neuropsychiatry, Nihon University School of Medicine (T. Kojima and S.T.), Department of Neuropsychiatry, Toho University School of Medicine (M.N.), Department of Psychiatry and Genome Research Center, Teikyo University School of Medicine (S.N.), Department of Psychiatry, Juntendo University School of Medicine (H.A. and T.O.), and Department of Schizophrenia Research, Tokyo Institute of Psychiatry (M.I.), Tokyo; Department of Psychiatry, University of Occupational and Environmental Health, Kitakyushu, Japan (O.O. and T. Shinkai); Department of Neuropsychiatry, Faculty of Medicine, Kagoshima University, Kagoshima, Japan (H.F. and T.H.); Department of Neuropsychiatry, School of Medicine, Fukushima Medical University, Fukushima, Japan (S.-i.N. and T.U.); Department of Mental Disorder Research, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Japan (H.K. and R.H.); Department of Psychiatry, School of Medicine, Nagoya University, Nagoya, Japan (N.O.); Department of Psychiatry, Fujita Health University School of Medicine, Toyoake, Japan (N.I.); Department of Neuropsychiatry, Kurume University School of Medicine, Kurume, Japan (M.H.); Department of Psychiatry, Hokkaido University School of Medicine, Sapporo, Japan (I.K. and T. Koyama); Department of Neuropsychiatry, Osaka Medical College, Takatsuki, Japan (H.Y.); Division of Disease Genes, Research Center for Genetic Information, Medical Institute of Bioregulation, Kyushu University, Fukuoka, Japan (Y.F. and H. Shibata); Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, Japan (S.K., H.H., and N.Y.-F.); Department of Psychobiology, Tohoku University Graduate School of Medicine, Sendai, Japan (Y.N.); and Department of Psychiatry, Mie University School of Medicine, Tsu, Japan (Y.O.).

Web Resources

The URLs for data presented herein are as follows:

  1. Center of Statistical Genetics, http://csg.sph.umich.edu/ (for the MERLIN program)
  2. GeneFinder, http://www.biostat.jhsph.edu/~wmchen/gf.html
  3. Haploview, http://www.broad.mit.edu/mpg/haploview/
  4. Institute of Cancer Research, http://www.icr.ac.uk/cancgen/molgen/MolPopGen_Bioinformatics.htm (for the SNPLINK program)
  5. NCBI, http://www.ncbi.nlm.nih.gov/mapview/map_search.cgi?taxid=9606 (for map view build 35 and identification of candidate genes in locus of interest)
  6. Online Mendelian Inheritance in Man (OMIM), http://www.ncbi.nlm.nih.gov/Omim/ (for schizophrenia, 6p24-p22, 1q21-q22, 13q32-q34, 8p22-p21, 6q21-q25, 22q11-q12, 5q21-q33, HTR2A, NTNG1, and NPAS3)

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