title: IgA measurements in over 12 000 Swedish twins reveal sex differential heritability and regulatory locus near CD30L.
abstract: In a broad attempt to improve the understanding of the genetic regulation of serum IgA levels, the heritability was estimated in over 12 000 Swedish twins, and a genome-wide association study was conducted in a subsample of 9617. Using the classical twin model the heritability was found to be significantly larger among females (61%) compared with males (21%), while contribution from shared environment (20%) was only seen for males. By modeling the genetic relationship matrix with IgA levels, we estimate that a substantial proportion (31%) of variance in IgA levels can ultimately be explained by the investigated SNPs. The genome-wide association study revealed significant association to two loci: (i) rs6928791 located on chromosome 6, 22 kb upstream of the gene SAM and SH3 domain containing 1 (SASH1) and (ii) rs13300483 on chromosome 9, situated 12 kb downstream the CD30 ligand (CD30L) encoding gene. The association to rs13300483 was replicated in two additional independent Swedish materials. The heritability of IgA levels is moderate and can partly be attributable to common variation in the CD30L locus.
authors.affiliation: Department of Medical Epidemiology and Biostatistics.
authors.forename: Alexander
authors.initials: A
authors.lastname: Viktorin
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Marcel
authors.initials: M
authors.lastname: Frankowiack
authors.affiliation: Rheumatology Unit, Department of Medicine and.
authors.forename: Leonid
authors.initials: L
authors.lastname: Padyukov
authors.affiliation: Department of Medical Epidemiology and Biostatistics.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Chang
authors.affiliation: Institute of Environmental Medicine and Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden Sachś Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
authors.forename: Erik
authors.initials: E
authors.lastname: Melén
authors.affiliation: Institute of Environmental Medicine and Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Sääf
authors.affiliation: Institute of Environmental Medicine and Centre for Allergy Research, Karolinska Institutet, Stockholm, Sweden Department of Clinical Science and Education, Södersjukhuset, Karolinska Institutet, Stockholm, Sweden Sachś Children and Youth Hospital, Södersjukhuset, Stockholm, Sweden.
authors.forename: Inger
authors.initials: I
authors.lastname: Kull
authors.affiliation: Rheumatology Unit, Department of Medicine and.
authors.forename: Lars
authors.initials: L
authors.lastname: Klareskog
authors.affiliation: Department of Laboratory Medicine.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hammarström
authors.affiliation: Department of Medical Epidemiology and Biostatistics, patrik.magnusson@ki.se.
authors.forename: Patrik K E
authors.initials: PK
authors.lastname: Magnusson
mesh_terms: D053285:CD30 Ligand / Q000235:genetics* / Q000276:immunology; D005260:Female; D059647:Gene-Environment Interaction; D056426:Genetic Loci; D015894:Genome, Human; D055106:Genome-Wide Association Study; D006801:Humans; D007070:Immunoglobulin A / Q000235:genetics*; D040582:Inheritance Patterns; D008297:Male; D020641:Polymorphism, Single Nucleotide; D012737:Sex Factors; D013548:Sweden; D014430:Twins, Monozygotic; D044465:White People
chemical_list: D053285:CD30 Ligand; D007070:Immunoglobulin A