Association and linkage of allelic variants of the dopamine transporter gene in ADHD
Previously, we had reported a genome-wide scan for attention-deficit/hyperactivity disorder (ADHD) in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 (parametric HLOD analysis under a dominant model) near the dopamine trans...
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| creator | FRIEDEL, S SAAR, K SCHERAG, A WINDEMUTH -KIESELBACH, C SCHIMMELMANN, B. G WEWETZER, C MEYER, J WARNKE, A LESCH, K. P REINHARDT, R HERPERTZ-DAHLMANN, B LINDER, M SAUER, S HINNEY, A REMSCHMIDT, H SCHÄFER, H KONRAD, K HÜBNER, N HEBEBRAND, J DEMPFLE, A WALITZA, S RENNER, T ROMANOS, M FREITAG, C SEITZ, C PALMASON, H |
| description | Previously, we had reported a genome-wide scan for attention-deficit/hyperactivity disorder (ADHD) in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 (parametric HLOD analysis under a dominant model) near the dopamine transporter gene (DAT1). We genotyped 30 single nucleotide polymorphisms (SNPs) in this candidate gene and its 5' region in 329 families (including the 102 initial families) with 523 affected offspring. We found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P=0.0046); (2) the global P-value for association of haplotypes was significant for block two upon correction for all (n=3) tested blocks (P=0.0048); (3) within block two we detected a nominal P=0.000034 for one specific marker combination. This CGC haplotype showed relative risks of 1.95 and 2.43 for heterozygous and homozygous carriers, respectively; and (4) finally, our linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains our linkage peak and that rs463379 (P |
| doi_str_mv | 10.1038/sj.mp.4001986 |
| format | Article |
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G ; WEWETZER, C ; MEYER, J ; WARNKE, A ; LESCH, K. P ; REINHARDT, R ; HERPERTZ-DAHLMANN, B ; LINDER, M ; SAUER, S ; HINNEY, A ; REMSCHMIDT, H ; SCHÄFER, H ; KONRAD, K ; HÜBNER, N ; HEBEBRAND, J ; DEMPFLE, A ; WALITZA, S ; RENNER, T ; ROMANOS, M ; FREITAG, C ; SEITZ, C ; PALMASON, H</creator><creatorcontrib>FRIEDEL, S ; SAAR, K ; SCHERAG, A ; WINDEMUTH -KIESELBACH, C ; SCHIMMELMANN, B. G ; WEWETZER, C ; MEYER, J ; WARNKE, A ; LESCH, K. P ; REINHARDT, R ; HERPERTZ-DAHLMANN, B ; LINDER, M ; SAUER, S ; HINNEY, A ; REMSCHMIDT, H ; SCHÄFER, H ; KONRAD, K ; HÜBNER, N ; HEBEBRAND, J ; DEMPFLE, A ; WALITZA, S ; RENNER, T ; ROMANOS, M ; FREITAG, C ; SEITZ, C ; PALMASON, H</creatorcontrib><description>Previously, we had reported a genome-wide scan for attention-deficit/hyperactivity disorder (ADHD) in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 (parametric HLOD analysis under a dominant model) near the dopamine transporter gene (DAT1). We genotyped 30 single nucleotide polymorphisms (SNPs) in this candidate gene and its 5' region in 329 families (including the 102 initial families) with 523 affected offspring. We found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P=0.0046); (2) the global P-value for association of haplotypes was significant for block two upon correction for all (n=3) tested blocks (P=0.0048); (3) within block two we detected a nominal P=0.000034 for one specific marker combination. This CGC haplotype showed relative risks of 1.95 and 2.43 for heterozygous and homozygous carriers, respectively; and (4) finally, our linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains our linkage peak and that rs463379 (P<0.05) is the only SNP of the above haplotype that contributed to the linkage signal. In sum, we have accumulated evidence that genetic variation at the DAT1 locus underlies our ADHD linkage peak on chromosome 5; additionally solid association for a single SNP and a haplotype were shown. Future studies are required to assess if variation at this locus also explains other positive linkage results obtained for chromosome 5p.</description><identifier>ISSN: 1359-4184</identifier><identifier>EISSN: 1476-5578</identifier><identifier>DOI: 10.1038/sj.mp.4001986</identifier><identifier>PMID: 17579611</identifier><language>eng</language><publisher>Basingstoke: Nature Publishing Group</publisher><subject>Adolescent ; Attention Deficit Disorder with Hyperactivity - genetics ; Attention deficit disorders. Hyperactivity ; Attention deficit hyperactivity disorder ; Biological and medical sciences ; Child ; Child & adolescent psychiatry ; Child clinical studies ; Chromosome 5 ; Chromosomes ; Chromosomes, Human, Pair 5 ; Diagnosis ; Dopamine ; Dopamine Plasma Membrane Transport Proteins - genetics ; Dopamine transporter ; Family Health ; Female ; Gene Frequency ; Genetic aspects ; Genetic diversity ; Genetic Predisposition to Disease ; Genetic variation ; Genomes ; Genotype ; Haplotypes ; Health aspects ; Humans ; Hyperactivity ; Linkage Disequilibrium ; Lod Score ; Male ; Medical sciences ; Physiological aspects ; Polymorphism, Single Nucleotide ; Psychology. Psychoanalysis. Psychiatry ; Psychopathology. Psychiatry ; Psychotherapy ; Risk assessment ; Risk factors ; Single-nucleotide polymorphism ; Statistics, Nonparametric</subject><ispartof>Molecular psychiatry, 2007-10, Vol.12 (10), p.923-933</ispartof><rights>2007 INIST-CNRS</rights><rights>COPYRIGHT 2007 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Oct 2007</rights><rights>Nature Publishing Group 2007.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c567t-ea87465236e242b871dd5a1007af4327939aef264a8900c7cc6bb15813d1da073</citedby><cites>FETCH-LOGICAL-c567t-ea87465236e242b871dd5a1007af4327939aef264a8900c7cc6bb15813d1da073</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>315,781,785,27928,27929</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=19087537$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/17579611$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>FRIEDEL, S</creatorcontrib><creatorcontrib>SAAR, K</creatorcontrib><creatorcontrib>SCHERAG, A</creatorcontrib><creatorcontrib>WINDEMUTH -KIESELBACH, C</creatorcontrib><creatorcontrib>SCHIMMELMANN, B. G</creatorcontrib><creatorcontrib>WEWETZER, C</creatorcontrib><creatorcontrib>MEYER, J</creatorcontrib><creatorcontrib>WARNKE, A</creatorcontrib><creatorcontrib>LESCH, K. P</creatorcontrib><creatorcontrib>REINHARDT, R</creatorcontrib><creatorcontrib>HERPERTZ-DAHLMANN, B</creatorcontrib><creatorcontrib>LINDER, M</creatorcontrib><creatorcontrib>SAUER, S</creatorcontrib><creatorcontrib>HINNEY, A</creatorcontrib><creatorcontrib>REMSCHMIDT, H</creatorcontrib><creatorcontrib>SCHÄFER, H</creatorcontrib><creatorcontrib>KONRAD, K</creatorcontrib><creatorcontrib>HÜBNER, N</creatorcontrib><creatorcontrib>HEBEBRAND, J</creatorcontrib><creatorcontrib>DEMPFLE, A</creatorcontrib><creatorcontrib>WALITZA, S</creatorcontrib><creatorcontrib>RENNER, T</creatorcontrib><creatorcontrib>ROMANOS, M</creatorcontrib><creatorcontrib>FREITAG, C</creatorcontrib><creatorcontrib>SEITZ, C</creatorcontrib><creatorcontrib>PALMASON, H</creatorcontrib><title>Association and linkage of allelic variants of the dopamine transporter gene in ADHD</title><title>Molecular psychiatry</title><addtitle>Mol Psychiatry</addtitle><description>Previously, we had reported a genome-wide scan for attention-deficit/hyperactivity disorder (ADHD) in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 (parametric HLOD analysis under a dominant model) near the dopamine transporter gene (DAT1). We genotyped 30 single nucleotide polymorphisms (SNPs) in this candidate gene and its 5' region in 329 families (including the 102 initial families) with 523 affected offspring. We found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P=0.0046); (2) the global P-value for association of haplotypes was significant for block two upon correction for all (n=3) tested blocks (P=0.0048); (3) within block two we detected a nominal P=0.000034 for one specific marker combination. This CGC haplotype showed relative risks of 1.95 and 2.43 for heterozygous and homozygous carriers, respectively; and (4) finally, our linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains our linkage peak and that rs463379 (P<0.05) is the only SNP of the above haplotype that contributed to the linkage signal. In sum, we have accumulated evidence that genetic variation at the DAT1 locus underlies our ADHD linkage peak on chromosome 5; additionally solid association for a single SNP and a haplotype were shown. Future studies are required to assess if variation at this locus also explains other positive linkage results obtained for chromosome 5p.</description><subject>Adolescent</subject><subject>Attention Deficit Disorder with Hyperactivity - genetics</subject><subject>Attention deficit disorders. Hyperactivity</subject><subject>Attention deficit hyperactivity disorder</subject><subject>Biological and medical sciences</subject><subject>Child</subject><subject>Child & adolescent psychiatry</subject><subject>Child clinical studies</subject><subject>Chromosome 5</subject><subject>Chromosomes</subject><subject>Chromosomes, Human, Pair 5</subject><subject>Diagnosis</subject><subject>Dopamine</subject><subject>Dopamine Plasma Membrane Transport Proteins - genetics</subject><subject>Dopamine transporter</subject><subject>Family Health</subject><subject>Female</subject><subject>Gene Frequency</subject><subject>Genetic aspects</subject><subject>Genetic diversity</subject><subject>Genetic Predisposition to Disease</subject><subject>Genetic variation</subject><subject>Genomes</subject><subject>Genotype</subject><subject>Haplotypes</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Hyperactivity</subject><subject>Linkage Disequilibrium</subject><subject>Lod Score</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Physiological aspects</subject><subject>Polymorphism, Single Nucleotide</subject><subject>Psychology. Psychoanalysis. Psychiatry</subject><subject>Psychopathology. Psychiatry</subject><subject>Psychotherapy</subject><subject>Risk assessment</subject><subject>Risk factors</subject><subject>Single-nucleotide polymorphism</subject><subject>Statistics, Nonparametric</subject><issn>1359-4184</issn><issn>1476-5578</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2007</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNqF0s2P1CAUAPDGaNx19ehR02jUU0deKV_Hya66Jpt4Wc_kDaUjYwsVWhP_e2mmOtH4kR5oHj94D3hF8RjIBgiVr9NhM4ybhhBQkt8pzqERvGJMyLv5nzJVNSCbs-JBSods8iS7X5yBYEJxgPPidptSMA4nF3yJvi175z_j3pahK7Hvbe9M-RWjQz-lJTZ9smUbRhyct-UU0acxxMnGcm9zwPlye3V99bC412Gf7KN1vCg-vn1ze3ld3Xx49_5ye1MZxsVUWZSi4aym3NZNvZMC2pYhECKwa2gtFFVou5o3KBUhRhjDdztgEmgLLRJBL4pXx33HGL7MNk16cMnYvkdvw5y0YIoC46TJ8uU_JZcUsoP_wnzLShJSZ_j8N3gIc_T5uDpXzATnIHlWz_6qasgpJRenrfbYW-18F_LFmiWv3oKUklAil8o2f1D5a-3gTPC2czn-y4LquMDEkFK0nR6jGzB-00D00js6HfQw6rV3sn-61jrvBtue9NosGbxYASaDfZdf37h0copIwehynidH53Gao_0JfiT6Drl10XA</recordid><startdate>20071001</startdate><enddate>20071001</enddate><creator>FRIEDEL, S</creator><creator>SAAR, K</creator><creator>SCHERAG, A</creator><creator>WINDEMUTH -KIESELBACH, C</creator><creator>SCHIMMELMANN, B. 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G ; WEWETZER, C ; MEYER, J ; WARNKE, A ; LESCH, K. P ; REINHARDT, R ; HERPERTZ-DAHLMANN, B ; LINDER, M ; SAUER, S ; HINNEY, A ; REMSCHMIDT, H ; SCHÄFER, H ; KONRAD, K ; HÜBNER, N ; HEBEBRAND, J ; DEMPFLE, A ; WALITZA, S ; RENNER, T ; ROMANOS, M ; FREITAG, C ; SEITZ, C ; PALMASON, H</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c567t-ea87465236e242b871dd5a1007af4327939aef264a8900c7cc6bb15813d1da073</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2007</creationdate><topic>Adolescent</topic><topic>Attention Deficit Disorder with Hyperactivity - genetics</topic><topic>Attention deficit disorders. 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We genotyped 30 single nucleotide polymorphisms (SNPs) in this candidate gene and its 5' region in 329 families (including the 102 initial families) with 523 affected offspring. We found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P=0.0046); (2) the global P-value for association of haplotypes was significant for block two upon correction for all (n=3) tested blocks (P=0.0048); (3) within block two we detected a nominal P=0.000034 for one specific marker combination. This CGC haplotype showed relative risks of 1.95 and 2.43 for heterozygous and homozygous carriers, respectively; and (4) finally, our linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains our linkage peak and that rs463379 (P<0.05) is the only SNP of the above haplotype that contributed to the linkage signal. In sum, we have accumulated evidence that genetic variation at the DAT1 locus underlies our ADHD linkage peak on chromosome 5; additionally solid association for a single SNP and a haplotype were shown. Future studies are required to assess if variation at this locus also explains other positive linkage results obtained for chromosome 5p.</abstract><cop>Basingstoke</cop><pub>Nature Publishing Group</pub><pmid>17579611</pmid><doi>10.1038/sj.mp.4001986</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1359-4184 |
| ispartof | Molecular psychiatry, 2007-10, Vol.12 (10), p.923-933 |
| issn | 1359-4184 1476-5578 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_759315604 |
| source | MEDLINE; Alma/SFX Local Collection |
| subjects | Adolescent Attention Deficit Disorder with Hyperactivity - genetics Attention deficit disorders. Hyperactivity Attention deficit hyperactivity disorder Biological and medical sciences Child Child & adolescent psychiatry Child clinical studies Chromosome 5 Chromosomes Chromosomes, Human, Pair 5 Diagnosis Dopamine Dopamine Plasma Membrane Transport Proteins - genetics Dopamine transporter Family Health Female Gene Frequency Genetic aspects Genetic diversity Genetic Predisposition to Disease Genetic variation Genomes Genotype Haplotypes Health aspects Humans Hyperactivity Linkage Disequilibrium Lod Score Male Medical sciences Physiological aspects Polymorphism, Single Nucleotide Psychology. Psychoanalysis. Psychiatry Psychopathology. Psychiatry Psychotherapy Risk assessment Risk factors Single-nucleotide polymorphism Statistics, Nonparametric |
| title | Association and linkage of allelic variants of the dopamine transporter gene in ADHD |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-17T02%3A50%3A45IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_proqu&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Association%20and%20linkage%20of%20allelic%20variants%20of%20the%20dopamine%20transporter%20gene%20in%20ADHD&rft.jtitle=Molecular%20psychiatry&rft.au=FRIEDEL,%20S&rft.date=2007-10-01&rft.volume=12&rft.issue=10&rft.spage=923&rft.epage=933&rft.pages=923-933&rft.issn=1359-4184&rft.eissn=1476-5578&rft_id=info:doi/10.1038/sj.mp.4001986&rft_dat=%3Cgale_proqu%3EA188803081%3C/gale_proqu%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=221160867&rft_id=info:pmid/17579611&rft_galeid=A188803081&rfr_iscdi=true |