TY  - JOUR
AB  - PURPOSE: Due to the increasing application of genome analysis and interpretation in medical disciplines, professionals require adequate education. Here, we present the implementation of personal genotyping as an educational tool in two genomics courses targeting Digital Health students at the Hasso Plattner Institute (HPI) and medical students at the Technical University of Munich (TUM). METHODS: We compared and evaluated the courses and the students' perceptions on the course setup using questionnaires. RESULTS: During the course, students changed their attitudes towards genotyping (HPI: 79% [15 of 19], TUM: 47% [25 of 53]). Predominantly, students became more critical of personal genotyping (HPI: 73% [11 of 15], TUM: 72% [18 of 25]) and most students stated that genetic analyses should not be allowed without genetic counseling (HPI: 79% [15 of 19], TUM: 70% [37 of 53]). Students found the personal genotyping component useful (HPI: 89% [17 of 19], TUM: 92% [49 of 53]) and recommended its inclusion in future courses (HPI: 95% [18 of 19], TUM: 98% [52 of 53]). CONCLUSION: Students perceived the personal genotyping component as valuable in the described genomics courses. The implementation described here can serve as an example for future courses in Europe.
AU  - Slosarek, T.*
AU  - Ibing, S.*
AU  - Schormair, B.
AU  - Heyne, H.O.*
AU  - Bottinger, E.P.*
AU  - Andlauer, T.F.M.*
AU  - Schurmann, C.*
C1  - 67628
C2  - 53935
CY  - Campus, 4 Crinan St, London N1 9xw, England
TI  - Implementation and evaluation of personal genetic testing as part of genomics analysis courses in German universities.
JO  - BMC Med. Genomics
VL  - 16
IS  - 1
PB  - Bmc
PY  - 2023
ER  - 

TY  - JOUR
AB  - BACKGROUND: Head circumference is associated with intelligence and tracks from childhood into adulthood. METHODS: We performed a genome-wide association study meta-analysis and follow-up of head circumference in a total of 29,192 participants between 6 and 30 months of age. RESULTS: Seven loci reached genome-wide significance in the combined discovery and replication analysis of which three loci near ARFGEF2, MYCL1, and TOP1, were novel. We observed positive genetic correlations for early-life head circumference with adult intracranial volume, years of schooling, childhood and adult intelligence, but not with adult psychiatric, neurological, or personality-related phenotypes. CONCLUSIONS: The results of this study indicate that the biological processes underlying early-life head circumference overlap largely with those of adult head circumference. The associations of early-life head circumference with cognitive outcomes across the life course are partly explained by genetics.
AU  - Vogelezang, S.*
AU  - Bradfield, J.P.*
AU  - Grant, S.F.A.*
AU  - Felix, J.F.*
AU  - Jaddoe, V.W.V.*
AU  - Early Growth Genetics Consortium (Standl, M.
AU  - Heinrich, J.
AU  - Thiering, E.
AU  - Waldenberger, M.
AU  - Panoutsopoulou, K.
AU  - Zeggini, E.)
C1  - 66505
C2  - 52861
TI  - Genetics of early-life head circumference and genetic correlations with neurological, psychiatric and cognitive outcomes.
JO  - BMC Med. Genomics
VL  - 15
IS  - 1
PY  - 2022
ER  - 

TY  - JOUR
AB  - Background Advanced age-related macular degeneration (AMD) is a leading cause of blindness. While around half of the genetic contribution to advanced AMD has been uncovered, little is known about the genetic architecture of early AMD. Methods To identify genetic factors for early AMD, we conducted a genome-wide association study (GWAS) meta-analysis (14,034 cases, 91,214 controls, 11 sources of data including the International AMD Genomics Consortium, IAMDGC, and UK Biobank, UKBB). We ascertained early AMD via color fundus photographs by manual grading for 10 sources and via an automated machine learning approach for > 170,000 photographs from UKBB. We searched for early AMD loci via GWAS and via a candidate approach based on 14 previously suggested early AMD variants. Results Altogether, we identified 10 independent loci with statistical significance for early AMD: (i) 8 from our GWAS with genome-wide significance (P < 5 x 10(- 8)), (ii) one previously suggested locus with experiment-wise significance (P < 0.05/14) in our non-overlapping data and with genome-wide significance when combining the reported and our non-overlapping data (together 17,539 cases, 105,395 controls), and (iii) one further previously suggested locus with experiment-wise significance in our non-overlapping data. Of these 10 identified loci, 8 were novel and 2 known for early AMD. Most of the 10 loci overlapped with known advanced AMD loci (nearARMS2/HTRA1, CFH,C2,C3,CETP,TNFRSF10A,VEGFA, APOE), except two that have not yet been identified with statistical significance for any AMD. Among the 17 genes within these two loci, in-silico functional annotation suggestedCD46andTYRas the most likely responsible genes. Presence or absence of an early AMD effect distinguished the known pathways of advanced AMD genetics (complement/lipid pathways versus extracellular matrix metabolism). Conclusions Our GWAS on early AMD identified novel loci, highlighted shared and distinct genetics between early and advanced AMD and provides insights into AMD etiology. Our data provide a resource comparable in size to the existing IAMDGC data on advanced AMD genetics enabling a joint view. The biological relevance of this joint view is underscored by the ability of early AMD effects to differentiate the major pathways for advanced AMD.
AU  - Winkler, T.W.*
AU  - Grassmann, F.*
AU  - Brandl, C.*
AU  - Kiel, C.*
AU  - Günther, F.*
AU  - Strunz, T.*
AU  - Weidner, L.*
AU  - Zimmermann, M.E.*
AU  - Korb, C.A.*
AU  - Poplawski, A.*
AU  - Schuster, A.K.*
AU  - Müller-Nurasyid, M.
AU  - Peters, A.
AU  - Rauscher, F.G.*
AU  - Elze, T.*
AU  - Horn, K.*
AU  - Scholz, M.*
AU  - Cañadas-Garre, M.*
AU  - McKnight, A.J.*
AU  - Quinn, N.*
AU  - Hogg, R.E.*
AU  - Küchenhoff, H.*
AU  - Heid, I.M.*
AU  - Stark, K.J.*
AU  - Weber, B.H.F.*
C1  - 59970
C2  - 48990
CY  - Campus, 4 Crinan St, London N1 9xw, England
TI  - Genome-wide association meta-analysis for early age-related macular degeneration highlights novel loci and insights for advanced disease.
JO  - BMC Med. Genomics
VL  - 13
IS  - 1
PB  - Bmc
PY  - 2020
ER  - 

TY  - JOUR
AB  - Background: Non-cellular blood circulating microRNAs (plasma miRNAs) represent a promising source for the development of prognostic and diagnostic tools owing to their minimally invasive sampling, high stability, and simple quantification by standard techniques such as RT-qPCR. So far, the majority of association studies involving plasma miRNAs were disease-specific case-control analyses. In contrast, in the present study, plasma miRNAs were analysed in a sample of 372 individuals from a population-based cohort study, the Study of Health in Pomerania (SHIP). Methods: Quantification of miRNA levels was performed by RT-qPCR using the Exiqon Serum/Plasma Focus microRNA PCR Panel V3.M covering 179 different miRNAs. Of these, 155 were included in our analyses after quality-control. Associations between plasma miRNAs and the phenotypes age, body mass index (BMI), and sex were assessed via a two-step linear regression approach per miRNA. The first step regressed out the technical parameters and the second step determined the remaining associations between the respective plasma miRNA and the phenotypes of interest. Results: After regressing out technical parameters and adjusting for the respective other two phenotypes, 7, 15, and 35 plasma miRNAs were significantly (q < 0.05) associated with age, BMI, and sex, respectively. Additional adjustment for the blood cell parameters identified 12 and 19 miRNAs to be significantly associated with age and BMI, respectively. Most of the BMI-associated miRNAs likely originate from liver. Sex-associated differences in miRNA levels were largely determined by differences in blood cell parameters. Thus, only 7 as compared to originally 35 sex-associated miRNAs displayed sex-specific differences after adjustment for blood cell parameters. Conclusions: These findings emphasize that circulating miRNAs are strongly impacted by age, BMI, and sex. Hence, these parameters should be considered as covariates in association studies based on plasma miRNA levels. The established experimental and computational workflow can now be used in future screening studies to determine associations of plasma miRNAs with defined disease phenotypes.
AU  - Ameling, S.*
AU  - Kacprowski, T.*
AU  - Chilukoti, R.K.*
AU  - Malsch, C.*
AU  - Liebscher, V.*
AU  - Suhre, K.
AU  - Pietzner, M.*
AU  - Friedrich, N.*
AU  - Homuth, G.*
AU  - Hammer, E.*
AU  - Völker, U.*
C1  - 47107
C2  - 39190
TI  - Associations of circulating plasma microRNAs with age, body mass index and sex in a population-based study.
JO  - BMC Med. Genomics
VL  - 8
PY  - 2015
ER  - 

TY  - JOUR
AB  - Background: Human endogenous retroviruses (HERVs) are flanked by long terminal repeats (LTRs), which possess promoter activity and can therefore influence the expression of neighboring genes. HERV involvement in different types of cancer has already been thoroughly documented. However, so far there has been no systematic study of HERV expression patterns in a multitude of cell types in health and disease. In particular, the publication of the comprehensive ENCODE dataset has already facilitated many gene expression studies, but none so far focusing exclusively on HERVs. Results: We present a comprehensive differential analysis of HERV expression based on ENCODE Tier 1 and Tier 2 RNA-seq data produced by Cold Spring Harbor Laboratories and the California Institute of Technology. This analysis was conducted for individual HERV loci and for entire HERV families in twelve different cell lines, of which six correspond to the normal condition and the other six represent cancer cell types. Although the principal component analysis revealed that the two groups of cells show distinguishable expression patterns, we were not able to link these differences to one or multiple particular HERV families. Two samples exhibit expression patterns, which are not similar to the corresponding cell lines of the other producing lab. Instead they show signs of cancer formation and expression of the pluripotency marker HERVH, despite being classified as a normal cell line and a differentiated cell, respectively. Conclusions: Our study demonstrates that ENCODE data are generally comparable between the different contributing labs and that the analysis of HERV elements can provide novel insights into differentiation and disease state of a cell that are easily overlooked when focusing on protein-coding genes. Our findings hint at a change in HERV expression during cancerogenesis.
AU  - Haase, K.*
AU  - Mösch, A.*
AU  - Frishman, D.
C1  - 47293
C2  - 40517
TI  - Differential expression analysis of human endogenous retroviruses based on ENCODE RNA-seq data.
JO  - BMC Med. Genomics
VL  - 8
PY  - 2015
ER  - 

TY  - JOUR
AB  - BACKGROUND: Obesity, defined as pathologically increased body mass index (BMI), is strongly related to an increased risk for numerous common cardiovascular and metabolic diseases. It is particularly associated with insulin resistance, hyperglycemia, and systemic oxidative stress and represents the most important risk factor for type 2 diabetes (T2D). However, the pathophysiological mechanisms underlying these associations are still not completely understood. Therefore, in order to identify potentially disease-relevant BMI-associated gene expression signatures, a transcriptome-wide association study (TWAS) on BMI was performed. METHODS: Whole-blood mRNA levels determined by array-based transcriptional profiling were correlated with BMI in two large independent population-based cohort studies (KORA F4 and SHIP-TREND) comprising a total of 1977 individuals. RESULTS: Extensive alterations of the whole-blood transcriptome were associated with BMI: More than 3500 transcripts exhibited significant positive or negative BMI-correlation. Three major whole-blood gene expression signatures associated with increased BMI were identified. The three signatures suggested: i) a ratio shift from mature erythrocytes towards reticulocytes, ii) decreased expression of several genes essentially involved in the transmission and amplification of the insulin signal, and iii) reduced expression of several key genes involved in the defence against reactive oxygen species (ROS). CONCLUSIONS: Whereas the first signature confirms published results, the other two provide possible mechanistic explanations for well-known epidemiological findings under conditions of increased BMI, namely attenuated insulin signaling and increased oxidative stress. The putatively causative BMI-dependent down-regulation of the expression of numerous genes on the mRNA level represents a novel finding. BMI-associated negative transcriptional regulation of insulin signaling and oxidative stress management provide new insights into the pathogenesis of metabolic syndrome and T2D.
AU  - Homuth, G.*
AU  - Wahl, S.
AU  - Mueller, C.*
AU  - Schurmann, C.*
AU  - Maeder, U.*
AU  - Blankenberg, S.*
AU  - Carstensen, M.*
AU  - Doerr, M.*
AU  - Endlich, K.*
AU  - Englbrecht, C.*
AU  - Felix, S.B.*
AU  - Gieger, C.
AU  - Grallert, H.
AU  - Herder, C.*
AU  - Illig, T.
AU  - Kruppa, J.*
AU  - Marzi, C.S.*
AU  - Mayerle, J.*
AU  - Meitinger, T.
AU  - Metspalu, A.*
AU  - Nauck, M.*
AU  - Peters, A.
AU  - Rathmann, W.*
AU  - Reinmaa, E.*
AU  - Rettig, R.*
AU  - Roden, M.*
AU  - Schillert, A.*
AU  - Schramm, K.
AU  - Steil, L.*
AU  - Strauch, K.
AU  - Teumer, A.*
AU  - Voelzke, H.*
AU  - Wallaschofski, H.*
AU  - Wild, P.S.*
AU  - Ziegler, A.*
AU  - Voelker, U.*
AU  - Prokisch, H.
AU  - Zeller, T.*
C1  - 47193
C2  - 39147
TI  - Extensive alterations of the whole-blood transcriptome are associated with body mass index: Results of an mRNA profiling study involving two large population-based cohorts.
JO  - BMC Med. Genomics
VL  - 8
IS  - 1
PY  - 2015
ER  - 

TY  - JOUR
AB  - BACKGROUND: The SH2B1 gene (Src-homology 2B adaptor protein 1 gene) is a solid candidate gene for obesity. Large scale GWAS studies depicted markers in the vicinity of the gene; animal models suggest a potential relevance for human body weight regulation. METHODS: We performed a mutation screen for variants in the SH2B1 coding sequence in 95 extremely obese children and adolescents. Detected variants were genotyped in independent childhood and adult study groups (up to 11,406 obese or overweight individuals and 4,568 controls). Functional implications on STAT3 mediated leptin signalling of the detected variants were analyzed in vitro. RESULTS: We identified two new rare mutations and five known SNPs (rs147094247, rs7498665, rs60604881, rs62037368 and rs62037369) in SH2B1. Mutation g.9483C/T leads to a non-synonymous, non-conservative exchange in the beta (βThr656Ile) and gamma (γPro674Ser) splice variants of SH2B1. It was additionally detected in two of 11,206 (extremely) obese or overweight children, adolescents and adults, but not in 4,506 population-based normal-weight or lean controls. The non-coding mutation g.10182C/A at the 3' end of SH2B1 was only detected in three obese individuals. For the non-synonymous SNP rs7498665 (Thr484Ala) we observed nominal over-transmission of the previously described risk allele in 705 obesity trios (nominal p = 0.009, OR = 1.23) and an increased frequency of the same allele in 359 cases compared to 429 controls (nominal p = 0.042, OR = 1.23). The obesity risk-alleles at Thr484Ala and βThr656Ile/γPro674Ser had no effect on STAT3 mediated leptin receptor signalling in splice variants β and γ. CONCLUSION: The rare coding mutation βThr656Ile/γPro674Ser (g.9483C/T) in SH2B1 was exclusively detected in overweight or obese individuals. Functional analyzes did not reveal impairments in leptin signalling for the mutated SH2B1.
AU  - Volckmar, A.-L.*
AU  - Bolze, F.*
AU  - Jarick, I.*
AU  - Knoll, N.*
AU  - Scherag, A.*
AU  - Reinehr, T.*
AU  - Illig, T.
AU  - Grallert, H.
AU  - Wichmann, H.-E.
AU  - Wiegand, S.*
AU  - Biebermann, H.*
AU  - Krude, H.*
AU  - Fischer-Posovszky, P.*
AU  - Rief, W.*
AU  - Wabitsch, M.*
AU  - Klingenspor, M.*
AU  - Hebebrand, J.*
AU  - Hinney, A.*
C1  - 22988
C2  - 30972
TI  - Mutation screen in the GWAS derived obesity gene SH2B1 including functional analyses of detected variants.
JO  - BMC Med. Genomics
VL  - 5
PB  - BioMed Central
PY  - 2012
ER  -