Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci
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Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci. / Fadista, Joao; Skotte, Line; Karjalainen, Juha; Abner, Erik; Sørensen, Erik; Ullum, Henrik; Werge, Thomas; Esko, Tõnu; Milani, Lili; Palotie, Aarno; Daly, Mark; Melbye, Mads; Feenstra, Bjarke; Geller, Frank; IPSYCH Grp; FinnGen Consortium.
I: Nature Communications, Bind 13, 3200, 2022.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Comprehensive genome-wide association study of different forms of hernia identifies more than 80 associated loci
AU - Fadista, Joao
AU - Skotte, Line
AU - Karjalainen, Juha
AU - Abner, Erik
AU - Sørensen, Erik
AU - Ullum, Henrik
AU - Werge, Thomas
AU - Esko, Tõnu
AU - Milani, Lili
AU - Palotie, Aarno
AU - Daly, Mark
AU - Melbye, Mads
AU - Feenstra, Bjarke
AU - Geller, Frank
AU - IPSYCH Grp
AU - FinnGen Consortium
PY - 2022
Y1 - 2022
N2 - Hernias are characterized by protrusion of an organ or tissue through its surrounding cavity and often require surgical repair. In this study we identify 65,492 cases for five hernia types in the UK Biobank and perform genome-wide association study scans for these five types and two combined groups. Our results show associated variants in all scans. Inguinal hernia has the most associations and we conduct a follow-up study with 23,803 additional cases from four study groups giving 84 independently associated variants. Identified variants from all scans are collapsed into 81 independent loci. Further testing shows that 26 loci are associated with more than one hernia type, suggesting substantial overlap between the underlying genetic mechanisms. Pathway analyses identify several genes with a strong link to collagen and/or elastin (ADAMTS6, ADAMTS16, ADAMTSL3, LOX, ELN) in the vicinity of associated loci for inguinal hernia, which substantiates an essential role of connective tissue morphology.Hernias involve protrusion of an organ or tissue through its surrounding cavity. Here the authors carry out GWAS for five types of hernia and find 81 variants, most of which are associated with inguinal hernia; downstream analysis suggests an important role for connective tissue morphology.
AB - Hernias are characterized by protrusion of an organ or tissue through its surrounding cavity and often require surgical repair. In this study we identify 65,492 cases for five hernia types in the UK Biobank and perform genome-wide association study scans for these five types and two combined groups. Our results show associated variants in all scans. Inguinal hernia has the most associations and we conduct a follow-up study with 23,803 additional cases from four study groups giving 84 independently associated variants. Identified variants from all scans are collapsed into 81 independent loci. Further testing shows that 26 loci are associated with more than one hernia type, suggesting substantial overlap between the underlying genetic mechanisms. Pathway analyses identify several genes with a strong link to collagen and/or elastin (ADAMTS6, ADAMTS16, ADAMTSL3, LOX, ELN) in the vicinity of associated loci for inguinal hernia, which substantiates an essential role of connective tissue morphology.Hernias involve protrusion of an organ or tissue through its surrounding cavity. Here the authors carry out GWAS for five types of hernia and find 81 variants, most of which are associated with inguinal hernia; downstream analysis suggests an important role for connective tissue morphology.
KW - LD SCORE REGRESSION
KW - MENDELIAN RANDOMIZATION
KW - INGUINAL-HERNIA
KW - HAPLOTYPE
KW - INFERENCE
KW - GENOTYPE
U2 - 10.1038/s41467-022-30921-4
DO - 10.1038/s41467-022-30921-4
M3 - Journal article
C2 - 35680855
VL - 13
JO - Nature Communications
JF - Nature Communications
SN - 2041-1723
M1 - 3200
ER -
ID: 312335950