References of "Ziegler, Andreas"
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See detailGenome-wide association study in musician's dystonia: a risk variant at the arylsulfatase G locus?
Lohmann, Katja; Schmidt, Alexander; Schillert, Arne et al

in Movement disorders : official journal of the Movement Disorder Society (2014), 29(7), 921-7

Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument ... [more ▼]

Musician's dystonia (MD) affects 1% to 2% of professional musicians and frequently terminates performance careers. It is characterized by loss of voluntary motor control when playing the instrument. Little is known about genetic risk factors, although MD or writer's dystonia (WD) occurs in relatives of 20% of MD patients. We conducted a 2-stage genome-wide association study in whites. Genotypes at 557,620 single-nucleotide polymorphisms (SNPs) passed stringent quality control for 127 patients and 984 controls. Ten SNPs revealed P < 10(-5) and entered the replication phase including 116 MD patients and 125 healthy musicians. A genome-wide significant SNP (P < 5 x 10(-8) ) was also genotyped in 208 German or Dutch WD patients, 1,969 Caucasian, Spanish, and Japanese patients with other forms of focal or segmental dystonia as well as in 2,233 ethnically matched controls. Genome-wide significance with MD was observed for an intronic variant in the arylsulfatase G (ARSG) gene (rs11655081; P = 3.95 x 10(-9) ; odds ratio [OR], 4.33; 95% confidence interval [CI], 2.66-7.05). rs11655081 was also associated with WD (P = 2.78 x 10(-2) ) but not with any other focal or segmental dystonia. The allele frequency of rs11655081 varies substantially between different populations. The population stratification in our sample was modest (lambda = 1.07), but the effect size may be overestimated. Using a small but homogenous patient sample, we provide data for a possible association of ARSG with MD. The variant may also contribute to the risk of WD, a form of dystonia that is often found in relatives of MD patients. [less ▲]

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See detailNext-generation phenotyping using the parkin example: time to catch up with genetics.
Grünewald, Anne UL; Kasten, Meike; Ziegler, Andreas et al

in JAMA neurology (2013), 70(9), 1186-91

IMPORTANCE: Two decades of intense research have led to important insights into the pathophysiology of neurodegenerative diseases, with limited direct clinical impact. While next-generation sequencing has ... [more ▼]

IMPORTANCE: Two decades of intense research have led to important insights into the pathophysiology of neurodegenerative diseases, with limited direct clinical impact. While next-generation sequencing has emerged as a powerful research tool, we hypothesized that systematic exploitation of phenotypic data are lagging behind genetic advances. OBJECTIVES: To use the 15-year experience with parkin-associated Parkinson disease (PD) to evaluate type, quality, and quantity of genetic and phenotypic data and to elucidate clinical or genetic features impacting genetic testing and counseling. EVIDENCE REVIEW: We searched MEDLINE: (1998-2012) using the term parkin AND mutation for English publications about proved parkin-associated PD and at least minimal, individual clinical information excluding digenic cases, and redundant articles. This approach identified 877 articles, of which 196 described patients with PD with confirmed parkin mutations and 127 articles fulfilled our inclusion criteria. Information was extracted using predefined criteria and a consensus approach for questionable details. To evaluate study method differences, we devised a quality score representing the completeness of clinical, demographic, and genetic information. FINDINGS: In the data about 1184 patients, the quality score increased steadily and was driven exclusively by improvements in genetic analyses. By contrast, demographic and clinical content stagnated. The mean age at onset was 9 years lower in index patients with 2 mutant parkin alleles than in heterozygotes. Genotype-phenotype correlation was observed for the number of mutated alleles and dystonia. By contrast, dementia was rare in all parkin-mutation carriers (<3%), despite long disease duration. CONCLUSIONS AND RELEVANCE: Notwithstanding large gaps in phenotypic information content, we identified dystonia and the absence of dementia as "red flags" to be incorporated in counseling guidelines. We propose mandatory minimal criteria for genotype-phenotype studies to facilitate the next breakthrough-following genetics-toward more personalized medicine for genetic conditions, extending well beyond the parkin example. [less ▲]

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