Family‐based association study of the restless legs syndrome loci 2 and 3 in a European population
Identifieur interne : 001E22 ( Istex/Corpus ); précédent : 001E21; suivant : 001E23Family‐based association study of the restless legs syndrome loci 2 and 3 in a European population
Auteurs : David Kemlink ; Olli Polo ; Pasquale Montagna ; Federica Provini ; Karin Stiasny-Kolster ; Wolfgang Oertel ; Al De Weerd ; Sona Nevsimalova ; Karel Sonka ; Birgit Högl ; Birgit Frauscher ; Werner Poewe ; Claudia Trenkwalder ; Peter P. Pramstaller ; Luigi Ferini-Strambi ; Marco Zucconi ; Eric Konofal ; Isabelle Arnulf ; Georgios M. Hadjigeorgiou ; Svenja Happe ; Christine Klein ; Anja Hiller ; Peter Lichtner ; Thomas Meitinger ; Betram Müller-Myshok ; Juliane WinkelmannSource :
- Movement Disorders [ 0885-3185 ] ; 2007-01-15.
English descriptors
Abstract
Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family‐based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846‐D9S171 in a subset of South European trios and with a haplotype at D9S156‐D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS. © 2006 Movement Disorder Society
Url:
DOI: 10.1002/mds.21254
Links to Exploration step
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<author><name sortKey="Ferini Trambi, Luigi" sort="Ferini Trambi, Luigi" uniqKey="Ferini Trambi L" first="Luigi" last="Ferini-Strambi">Luigi Ferini-Strambi</name>
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<author><name sortKey="Zucconi, Marco" sort="Zucconi, Marco" uniqKey="Zucconi M" first="Marco" last="Zucconi">Marco Zucconi</name>
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<author><name sortKey="Arnulf, Isabelle" sort="Arnulf, Isabelle" uniqKey="Arnulf I" first="Isabelle" last="Arnulf">Isabelle Arnulf</name>
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<author><name sortKey="Happe, Svenja" sort="Happe, Svenja" uniqKey="Happe S" first="Svenja" last="Happe">Svenja Happe</name>
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<author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name>
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<author><name sortKey="Hiller, Anja" sort="Hiller, Anja" uniqKey="Hiller A" first="Anja" last="Hiller">Anja Hiller</name>
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<affiliation><mods:affiliation>Technical University, Institute of Human Genetics, Munich, Germany</mods:affiliation>
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<affiliation><mods:affiliation>Technical University, Institute of Human Genetics, Munich, Germany</mods:affiliation>
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<author><name sortKey="Muller Yshok, Betram" sort="Muller Yshok, Betram" uniqKey="Muller Yshok B" first="Betram" last="Müller-Myshok">Betram Müller-Myshok</name>
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<author><name sortKey="Winkelmann, Juliane" sort="Winkelmann, Juliane" uniqKey="Winkelmann J" first="Juliane" last="Winkelmann">Juliane Winkelmann</name>
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<sourceDesc><biblStruct><analytic><title level="a" type="main" xml:lang="en">Family‐based association study of the restless legs syndrome loci 2 and 3 in a European population</title>
<author><name sortKey="Kemlink, David" sort="Kemlink, David" uniqKey="Kemlink D" first="David" last="Kemlink">David Kemlink</name>
<affiliation><mods:affiliation>Institute of Human Genetics, GSF‐National Research Center for Environment and Health, Munich, Germany</mods:affiliation>
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<author><name sortKey="Montagna, Pasquale" sort="Montagna, Pasquale" uniqKey="Montagna P" first="Pasquale" last="Montagna">Pasquale Montagna</name>
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<author><name sortKey="Provini, Federica" sort="Provini, Federica" uniqKey="Provini F" first="Federica" last="Provini">Federica Provini</name>
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<author><name sortKey="Stiasny Olster, Karin" sort="Stiasny Olster, Karin" uniqKey="Stiasny Olster K" first="Karin" last="Stiasny-Kolster">Karin Stiasny-Kolster</name>
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</affiliation>
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<author><name sortKey="Oertel, Wolfgang" sort="Oertel, Wolfgang" uniqKey="Oertel W" first="Wolfgang" last="Oertel">Wolfgang Oertel</name>
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</affiliation>
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<author><name sortKey="Nevsimalova, Sona" sort="Nevsimalova, Sona" uniqKey="Nevsimalova S" first="Sona" last="Nevsimalova">Sona Nevsimalova</name>
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</affiliation>
</author>
<author><name sortKey="Sonka, Karel" sort="Sonka, Karel" uniqKey="Sonka K" first="Karel" last="Sonka">Karel Sonka</name>
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</affiliation>
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<author><name sortKey="Hogl, Birgit" sort="Hogl, Birgit" uniqKey="Hogl B" first="Birgit" last="Högl">Birgit Högl</name>
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</affiliation>
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<author><name sortKey="Frauscher, Birgit" sort="Frauscher, Birgit" uniqKey="Frauscher B" first="Birgit" last="Frauscher">Birgit Frauscher</name>
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</affiliation>
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<author><name sortKey="Poewe, Werner" sort="Poewe, Werner" uniqKey="Poewe W" first="Werner" last="Poewe">Werner Poewe</name>
<affiliation><mods:affiliation>University Clinic Innsbruck, Neurology, Innsbruck, Austria</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Trenkwalder, Claudia" sort="Trenkwalder, Claudia" uniqKey="Trenkwalder C" first="Claudia" last="Trenkwalder">Claudia Trenkwalder</name>
<affiliation><mods:affiliation>Paracelsius‐Elena Klinik, Kassel, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Pramstaller, Peter P" sort="Pramstaller, Peter P" uniqKey="Pramstaller P" first="Peter P." last="Pramstaller">Peter P. Pramstaller</name>
<affiliation><mods:affiliation>Institute of Genetic Medicine, EURAC research, Bolzano, Italy</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Ferini Trambi, Luigi" sort="Ferini Trambi, Luigi" uniqKey="Ferini Trambi L" first="Luigi" last="Ferini-Strambi">Luigi Ferini-Strambi</name>
<affiliation><mods:affiliation>Università Vita‐Salute San Raffaele, Sleep Disorders Center, Milan, Italy</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Zucconi, Marco" sort="Zucconi, Marco" uniqKey="Zucconi M" first="Marco" last="Zucconi">Marco Zucconi</name>
<affiliation><mods:affiliation>Università Vita‐Salute San Raffaele, Sleep Disorders Center, Milan, Italy</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Konofal, Eric" sort="Konofal, Eric" uniqKey="Konofal E" first="Eric" last="Konofal">Eric Konofal</name>
<affiliation><mods:affiliation>Federation des Pathologies du Sommeil, Groupe Hospitalier Pitie‐Salpetriere, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Arnulf, Isabelle" sort="Arnulf, Isabelle" uniqKey="Arnulf I" first="Isabelle" last="Arnulf">Isabelle Arnulf</name>
<affiliation><mods:affiliation>Federation des Pathologies du Sommeil, Groupe Hospitalier Pitie‐Salpetriere, Paris, France</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Hadjigeorgiou, Georgios M" sort="Hadjigeorgiou, Georgios M" uniqKey="Hadjigeorgiou G" first="Georgios M." last="Hadjigeorgiou">Georgios M. Hadjigeorgiou</name>
<affiliation><mods:affiliation>University of Thessaly, Medical School, Department of Neurology, Thessaly, Greece</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Happe, Svenja" sort="Happe, Svenja" uniqKey="Happe S" first="Svenja" last="Happe">Svenja Happe</name>
<affiliation><mods:affiliation>Georg‐August‐University Göttingen Department Clinical Neurophysiology, Göttingen, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Klein, Christine" sort="Klein, Christine" uniqKey="Klein C" first="Christine" last="Klein">Christine Klein</name>
<affiliation><mods:affiliation>University of Lübeck, Department of Neurology, Lübeck, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Hiller, Anja" sort="Hiller, Anja" uniqKey="Hiller A" first="Anja" last="Hiller">Anja Hiller</name>
<affiliation><mods:affiliation>University of Lübeck, Department of Neurology, Lübeck, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Lichtner, Peter" sort="Lichtner, Peter" uniqKey="Lichtner P" first="Peter" last="Lichtner">Peter Lichtner</name>
<affiliation><mods:affiliation>Institute of Human Genetics, GSF‐National Research Center for Environment and Health, Munich, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Technical University, Institute of Human Genetics, Munich, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Meitinger, Thomas" sort="Meitinger, Thomas" uniqKey="Meitinger T" first="Thomas" last="Meitinger">Thomas Meitinger</name>
<affiliation><mods:affiliation>Institute of Human Genetics, GSF‐National Research Center for Environment and Health, Munich, Germany</mods:affiliation>
</affiliation>
<affiliation><mods:affiliation>Technical University, Institute of Human Genetics, Munich, Germany</mods:affiliation>
</affiliation>
</author>
<author><name sortKey="Muller Yshok, Betram" sort="Muller Yshok, Betram" uniqKey="Muller Yshok B" first="Betram" last="Müller-Myshok">Betram Müller-Myshok</name>
<affiliation><mods:affiliation>Max Planck Institute of Psychiatry, Munich, Germany</mods:affiliation>
</affiliation>
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<author><name sortKey="Winkelmann, Juliane" sort="Winkelmann, Juliane" uniqKey="Winkelmann J" first="Juliane" last="Winkelmann">Juliane Winkelmann</name>
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<affiliation><mods:affiliation>Max Planck Institute of Psychiatry, Munich, Germany</mods:affiliation>
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<series><title level="j">Movement Disorders</title>
<title level="j" type="sub">Official Journal of the Movement Disorder Society</title>
<title level="j" type="abbrev">Mov. Disord.</title>
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<date type="published" when="2007-01-15">2007-01-15</date>
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<profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>RLS1</term>
<term>RLS2</term>
<term>RLS3</term>
<term>genetics</term>
<term>restless legs syndrome</term>
<term>transmission disequilibrium test</term>
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<front><div type="abstract" xml:lang="en">Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family‐based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846‐D9S171 in a subset of South European trios and with a haplotype at D9S156‐D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS. © 2006 Movement Disorder Society</div>
</front>
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<author><json:item><name>David Kemlink MD</name>
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<json:item><name>Olli Polo MD</name>
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<json:item><name>Pasquale Montagna MD</name>
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<keywordGroup xml:lang="en" type="author"><keyword xml:id="kwd1">restless legs syndrome</keyword>
<keyword xml:id="kwd2">genetics</keyword>
<keyword xml:id="kwd3">transmission disequilibrium test</keyword>
<keyword xml:id="kwd4">RLS1</keyword>
<keyword xml:id="kwd5">RLS2</keyword>
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<fundingNumber>IGA MZ CR 8086‐3/2004</fundingNumber>
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<abstractGroup><abstract type="main" xml:lang="en"><title type="main">Abstract</title>
<p>Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family‐based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical <i>P</i>
values were estimated by permutation testing. On chromosome 14q, a significant association (empirical <i>P</i>
= 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846‐D9S171 in a subset of South European trios and with a haplotype at D9S156‐D9S157 in a subset of Central European trios (<i>P</i>
= 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS. © 2006 Movement Disorder Society</p>
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<abstract lang="en">Three loci for the restless legs syndrome (RLS) on chromosomes 12q, 14q, and 9p (RLS1, RLS2, and RLS3) have been mapped, but no gene has been identified as yet. RLS1 has been confirmed in families from three different populations. We conducted a family‐based association study of 159 European RLS trios. The subjects were genotyped using microsatellite markers evenly covering the candidate regions on chromosomes 14q and 9p with an average intermarker distance of 1.1 cM. Transmission disequilibrium tests were used to analyze the data, and empirical P values were estimated by permutation testing. On chromosome 14q, a significant association (empirical P = 0.0033) was found with a haplotype formed by markers D14S1014 and D14S1017 when analyzing all families. On chromosome 9p, no significant association in the sample of all families and only marginally significant associations were detected, with a haplotype involving markers D9S1846‐D9S171 in a subset of South European trios and with a haplotype at D9S156‐D9S157 in a subset of Central European trios (P = 0.0086 and 0.0077, respectively). These results represent the first confirmation of these loci in a mixed European population. Variable results observed in families of different ethnic groups further corroborate the genetic complexity of RLS. © 2006 Movement Disorder Society</abstract>
<note type="funding">International RLS Foundation</note>
<note type="funding">Czech Ministry of Health - No. IGA MZ CR 8086‐3/2004; </note>
<subject lang="en"><genre>Keywords</genre>
<topic>restless legs syndrome</topic>
<topic>genetics</topic>
<topic>transmission disequilibrium test</topic>
<topic>RLS1</topic>
<topic>RLS2</topic>
<topic>RLS3</topic>
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<identifier type="ISSN">0885-3185</identifier>
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<identifier type="DOI">10.1002/(ISSN)1531-8257</identifier>
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<part><date>2007</date>
<detail type="volume"><caption>vol.</caption>
<number>22</number>
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