TY  - JOUR
A1  - Tanoey, Justine
A1  - Baechle, Christina
A1  - Brenner, Hermann
A1  - Deckert, Andreas
A1  - Fricke, Julia
A1  - Günther, Kathrin
A1  - Karch, André
A1  - Keil, Thomas
A1  - Kluttig, Alexander
A1  - Leitzmann, Michael
A1  - Mikolajczyk, Rafael
A1  - Obi, Nadia
A1  - Pischon, Tobias
A1  - Schikowski, Tamara
A1  - Schipf, Sabine M.
A1  - Schulze, Matthias B.
A1  - Sedlmeier, Anja
A1  - Moreno Velásquez, Ilais
A1  - Weber, Katharina S.
A1  - Völzke, Henry
A1  - Ahrens, Wolfgang
A1  - Gastell, Sylvia
A1  - Holleczek, Bernd
A1  - Jöckel, Karl-Heinz
A1  - Katzke, Verena
A1  - Lieb, Wolfgang
A1  - Michels, Karin B.
A1  - Schmidt, Börge
A1  - Teismann, Henning
A1  - Becher, Heiko
T1  - Birth order, Caesarean section, or daycare attendance in relation to child- and adult-onset type 1 diabetes: results from the German National Cohort
JF  - International Journal of Environmental Research and Public Health
N2  - (1) Background: Global incidence of type 1 diabetes (T1D) is rising and nearly half occurred in adults. However, it is unclear if certain early-life childhood T1D risk factors were also associated with adult-onset T1D. This study aimed to assess associations between birth order, delivery mode or daycare attendance and type 1 diabetes (T1D) risk in a population-based cohort and whether these were similar for childhood- and adult-onset T1D (cut-off age 15); (2) Methods: Data were obtained from the German National Cohort (NAKO Gesundheitsstudie) baseline assessment. Self-reported diabetes was classified as T1D if: diagnosis age ≤ 40 years and has been receiving insulin treatment since less than one year after diagnosis. Cox regression was applied for T1D risk analysis; (3) Results: Analyses included 101,411 participants (100 childhood- and 271 adult-onset T1D cases). Compared to “only-children”, HRs for second- or later-born individuals were 0.70 (95% CI = 0.50–0.96) and 0.65 (95% CI = 0.45–0.94), respectively, regardless of parental diabetes, migration background, birth year and perinatal factors. In further analyses, higher birth order reduced T1D risk in children and adults born in recent decades. Caesarean section and daycare attendance showed no clear associations with T1D risk; (4) Conclusions: Birth order should be considered in both children and adults’ T1D risk assessment for early detection.
KW  - perinatal
KW  - adult-onset
KW  - late-onset
KW  - autoimmune
KW  - delivery mode
KW  - sex
KW  - offspring
KW  - NAKO
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-286216
SN  - 1660-4601
VL  - 19
IS  - 17
ER  - 
TY  - JOUR
A1  - Gómez-Fernández, Paloma
A1  - Lopez de Lapuente Portilla, Aitzkoa
A1  - Astobiza, Ianire
A1  - Mena, Jorge
A1  - Urtasun, Andoni
A1  - Altmann, Vivian
A1  - Matesanz, Fuencisla
A1  - Otaegui, David
A1  - Urcelay, Elena
A1  - Antigüedad, Alfredo
A1  - Malhotra, Sunny
A1  - Montalban, Xavier
A1  - Castillo-Triviño, Tamara
A1  - Espino-Paisán, Laura
A1  - Aktas, Orhan
A1  - Buttmann, Mathias
A1  - Chan, Andrew
A1  - Fontaine, Bertrand
A1  - Gourraud, Pierre-Antoine
A1  - Hecker, Michael
A1  - Hoffjan, Sabine
A1  - Kubisch, Christian
A1  - Kümpfel, Tania
A1  - Luessi, Felix
A1  - Zettl, Uwe K.
A1  - Zipp, Frauke
A1  - Alloza, Iraide
A1  - Comabella, Manuel
A1  - Lill, Christina M.
A1  - Vandenbroeck, Koen
T1  - The rare IL22RA2 signal peptide coding variant rs28385692 decreases secretion of IL-22BP isoform-1, -2 and -3 and is associated with risk for multiple sclerosis
JF  - Cells
N2  - The IL22RA2 locus is associated with risk for multiple sclerosis (MS) but causative variants are yet to be determined. In a single nucleotide polymorphism (SNP) screen of this locus in a Basque population, rs28385692, a rare coding variant substituting Leu for Pro at position 16 emerged significantly (p = 0.02). This variant is located in the signal peptide (SP) shared by the three secreted protein isoforms produced by IL22RA2 (IL-22 binding protein-1(IL-22BPi1), IL-22BPi2 and IL-22BPi3). Genotyping was extended to a Europe-wide case-control dataset and yielded high significance in the full dataset (p = 3.17 × 10\(^{-4}\)). Importantly, logistic regression analyses conditioning on the main known MS-associated SNP at this locus, rs17066096, revealed that this association was independent from the primary association signal in the full case-control dataset. In silico analysis predicted both disruption of the alpha helix of the H-region of the SP and decreased hydrophobicity of this region, ultimately affecting the SP cleavage site. We tested the effect of the p.Leu16Pro variant on the secretion of IL-22BPi1, IL-22BPi2 and IL-22BPi3 and observed that the Pro16 risk allele significantly lowers secretion levels of each of the isoforms to around 50%–60% in comparison to the Leu16 reference allele. Thus, our study suggests that genetically coded decreased levels of IL-22BP isoforms are associated with augmented risk for MS.
KW  - IL22RA2
KW  - IL-22 binding protein isoform
KW  - mutation
KW  - signal peptide
KW  - multiple sclerosis
KW  - autoimmune
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200769
SN  - 2073-4409
VL  - 9
IS  - 1
ER  -