A novel c.5308 5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia-0

4, II-5, II-7, II-9, II-13, II-14 and II-15). Haplotypes were constructed using the order in which the microsatellite marker loci are located in the region; D9S115, D9S1831, D9S179, D9S1830 and D9S164. Affected individuals (II-2, II-3, II-9 and II-14) are homozygous for the 5-2-2-1-1 haplotype. PCR and agarose gel electrophoresis based mutation detection results are also shown below the corresponding individual. A 105 bp band denotes a normal sequence and a 101 bp band denotes a deleted sequence (c.5308_5311delGAGA). Homozygous normal individuals (II-4) have a single 105 bp band, homozygous mutant individuals (II-2, II-3, II-9 and II-14) have a single band of 101 bp and heterozygous mutation carrier individuals (I-2, II-5, II-13 and II-15) have two bands of 105 and 101 bp.<p><b>Copyright information:</b></p><p>Taken from "A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia"</p><p>http://www.biomedcentral.com/1471-2350/9/28</p><p>BMC Medical Genetics 2008;9():28-28.</p><p>Published online 14 Apr 2008</p><p>PMCID:PMC2330029.</p><p></p

A novel c.5308 5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia-1

<p><b>Copyright information:</b></p><p>Taken from "A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia"</p><p>http://www.biomedcentral.com/1471-2350/9/28</p><p>BMC Medical Genetics 2008;9():28-28.</p><p>Published online 14 Apr 2008</p><p>PMCID:PMC2330029.</p><p></p

A novel c.5308 5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia-2

4, II-5, II-7, II-9, II-13, II-14 and II-15). Haplotypes were constructed using the order in which the microsatellite marker loci are located in the region; D9S115, D9S1831, D9S179, D9S1830 and D9S164. Affected individuals (II-2, II-3, II-9 and II-14) are homozygous for the 5-2-2-1-1 haplotype. PCR and agarose gel electrophoresis based mutation detection results are also shown below the corresponding individual. A 105 bp band denotes a normal sequence and a 101 bp band denotes a deleted sequence (c.5308_5311delGAGA). Homozygous normal individuals (II-4) have a single 105 bp band, homozygous mutant individuals (II-2, II-3, II-9 and II-14) have a single band of 101 bp and heterozygous mutation carrier individuals (I-2, II-5, II-13 and II-15) have two bands of 105 and 101 bp.<p><b>Copyright information:</b></p><p>Taken from "A novel c.5308_5311delGAGA mutation in Senataxin in a Cypriot family with an autosomal recessive cerebellar ataxia"</p><p>http://www.biomedcentral.com/1471-2350/9/28</p><p>BMC Medical Genetics 2008;9():28-28.</p><p>Published online 14 Apr 2008</p><p>PMCID:PMC2330029.</p><p></p

Odds Ratios (95% Confidence Intervals) showing associations between mitochondrial haplogroup clusters and superclusters and PD.

<p>Odds Ratios (95% Confidence Intervals) showing associations between mitochondrial haplogroup clusters and superclusters and PD.</p

Distribution of mtDNA haplogroups between Cypriot PD patients and controls and Odds Ratios (95% Confidence Intervals) showing their association with PD.

<p>Distribution of mtDNA haplogroups between Cypriot PD patients and controls and Odds Ratios (95% Confidence Intervals) showing their association with PD.</p

Table_1_PheWAS and cross-disorder analysis reveal genetic architecture, pleiotropic loci and phenotypic correlations across 11 autoimmune disorders.xlsx

IntroductionAutoimmune disorders (ADs) are a group of about 80 disorders that occur when self-attacking autoantibodies are produced due to failure in the self-tolerance mechanisms. ADs are polygenic disorders and associations with genes both in the human leukocyte antigen (HLA) region and outside of it have been described. Previous studies have shown that they are highly comorbid with shared genetic risk factors, while epidemiological studies revealed associations between various lifestyle and health-related phenotypes and ADs.MethodsHere, for the first time, we performed a comparative polygenic risk score (PRS) - Phenome Wide Association Study (PheWAS) for 11 different ADs (Juvenile Idiopathic Arthritis, Primary Sclerosing Cholangitis, Celiac Disease, Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Myasthenia Gravis, Type 1 Diabetes, Systemic Lupus Erythematosus, Vitiligo Late Onset, Vitiligo Early Onset) and 3,254 phenotypes available in the UK Biobank that include a wide range of socio-demographic, lifestyle and health-related outcomes. Additionally, we investigated the genetic relationships of the studied ADs, calculating their genetic correlation and conducting cross-disorder GWAS meta-analyses for the observed AD clusters.ResultsIn total, we identified 508 phenotypes significantly associated with at least one AD PRS. 272 phenotypes were significantly associated after excluding variants in the HLA region from the PRS estimation. Through genetic correlation and genetic factor analyses, we identified four genetic factors that run across studied ADs. Cross-trait meta-analyses within each factor revealed pleiotropic genome-wide significant loci.DiscussionOverall, our study confirms the association of different factors with genetic susceptibility for ADs and reveals novel observations that need to be further explored.</p

DataSheet_1_PheWAS and cross-disorder analysis reveal genetic architecture, pleiotropic loci and phenotypic correlations across 11 autoimmune disorders.pdf

IntroductionAutoimmune disorders (ADs) are a group of about 80 disorders that occur when self-attacking autoantibodies are produced due to failure in the self-tolerance mechanisms. ADs are polygenic disorders and associations with genes both in the human leukocyte antigen (HLA) region and outside of it have been described. Previous studies have shown that they are highly comorbid with shared genetic risk factors, while epidemiological studies revealed associations between various lifestyle and health-related phenotypes and ADs.MethodsHere, for the first time, we performed a comparative polygenic risk score (PRS) - Phenome Wide Association Study (PheWAS) for 11 different ADs (Juvenile Idiopathic Arthritis, Primary Sclerosing Cholangitis, Celiac Disease, Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Myasthenia Gravis, Type 1 Diabetes, Systemic Lupus Erythematosus, Vitiligo Late Onset, Vitiligo Early Onset) and 3,254 phenotypes available in the UK Biobank that include a wide range of socio-demographic, lifestyle and health-related outcomes. Additionally, we investigated the genetic relationships of the studied ADs, calculating their genetic correlation and conducting cross-disorder GWAS meta-analyses for the observed AD clusters.ResultsIn total, we identified 508 phenotypes significantly associated with at least one AD PRS. 272 phenotypes were significantly associated after excluding variants in the HLA region from the PRS estimation. Through genetic correlation and genetic factor analyses, we identified four genetic factors that run across studied ADs. Cross-trait meta-analyses within each factor revealed pleiotropic genome-wide significant loci.DiscussionOverall, our study confirms the association of different factors with genetic susceptibility for ADs and reveals novel observations that need to be further explored.</p

Table_2_PheWAS and cross-disorder analysis reveal genetic architecture, pleiotropic loci and phenotypic correlations across 11 autoimmune disorders.xlsx

IntroductionAutoimmune disorders (ADs) are a group of about 80 disorders that occur when self-attacking autoantibodies are produced due to failure in the self-tolerance mechanisms. ADs are polygenic disorders and associations with genes both in the human leukocyte antigen (HLA) region and outside of it have been described. Previous studies have shown that they are highly comorbid with shared genetic risk factors, while epidemiological studies revealed associations between various lifestyle and health-related phenotypes and ADs.MethodsHere, for the first time, we performed a comparative polygenic risk score (PRS) - Phenome Wide Association Study (PheWAS) for 11 different ADs (Juvenile Idiopathic Arthritis, Primary Sclerosing Cholangitis, Celiac Disease, Multiple Sclerosis, Rheumatoid Arthritis, Psoriasis, Myasthenia Gravis, Type 1 Diabetes, Systemic Lupus Erythematosus, Vitiligo Late Onset, Vitiligo Early Onset) and 3,254 phenotypes available in the UK Biobank that include a wide range of socio-demographic, lifestyle and health-related outcomes. Additionally, we investigated the genetic relationships of the studied ADs, calculating their genetic correlation and conducting cross-disorder GWAS meta-analyses for the observed AD clusters.ResultsIn total, we identified 508 phenotypes significantly associated with at least one AD PRS. 272 phenotypes were significantly associated after excluding variants in the HLA region from the PRS estimation. Through genetic correlation and genetic factor analyses, we identified four genetic factors that run across studied ADs. Cross-trait meta-analyses within each factor revealed pleiotropic genome-wide significant loci.DiscussionOverall, our study confirms the association of different factors with genetic susceptibility for ADs and reveals novel observations that need to be further explored.</p