Female-Specific Association Between Variants on Chromosome 9 and Self-Reported Diagnosis of Irritable Bowel Syndrome.
Обработка статьи · этапы, ошибки и управление
Ошибки и ограничения
История · было → стало
Состояние обновляется каждые 5 секунд, пока блок открыт. Процент показывается только там, где известен объём работы. Пауза останавливает продолжение этапа; текущий запрос к источнику может завершиться.
Bonfiglio Ferdinando, Zheng Tenghao, Garcia-Etxebarria Koldo, Hadizadeh Fatemeh, Bujanda Luis, Bresso Francesca, Agreus Lars, Andreasson Anna, Dlugosz Aldona, Lindberg Greger, Schmidt Peter T, Karling Pontus, Ohlsson Bodil, Simren Magnus, Walter Susanna, Nardone Gerardo, Cuomo Rosario, Usai-Satta Paolo, Galeazzi Francesca, Neri Matteo, Portincasa Piero, Bellini Massimo, Barbara Giovanni, Latiano Anna, Hübenthal Matthias, Thijs Vincent, Netea Mihai G, Jonkers Daisy, Chang Lin, Mayer Emeran A, Wouters Mira M, Boeckxstaens Guy, Camilleri Michael, Franke Andre, Zhernakova Alexandra, D'Amato Mauro
Аннотация
METHODS: We studied 7,287,191 high-quality single nucleotide polymorphisms in individuals who self-reported a doctor's diagnosis of IBS (cases; n = 9576) compared to the remainder of the cohort (controls; n = 336,499) (mean age of study subjects, 40-69 years). Genome-wide significant findings were further investigated in 2045 patients with IBS from tertiary centers and 7955 population controls from Europe and the United States, and a small general population sample from Sweden (n = 249). Functional annotation of GWAS results was carried out by integrating data from multiple biorepositories to obtain biological insights from the observed associations.
RESULTS: We identified a genome-wide significant association on chromosome 9q31.2 (single nucleotide polymorphism rs10512344; P = 3.57 × 10-8) in a region previously linked to age at menarche, and 13 additional loci of suggestive significance (P < 5.0×10-6). Sex-stratified analyses revealed that the variants at 9q31.2 affect risk of IBS in women only (P = 4.29 × 10-10 in UK Biobank) and also associate with constipation-predominant IBS in women (P = .015 in the tertiary cohort) and harder stools in women (P = .0012 in the population-based sample). Functional annotation of the 9q31.2 locus identified 8 candidate genes, including the elongator complex protein 1 gene (ELP1 or IKBKAP), which is mutated in patients with familial dysautonomia.
CONCLUSIONS: In a sufficiently powered GWAS of IBS, we associated variants at the locus 9q31.2 with risk of IBS in women. This observation may provide additional rationale for investigating the role of sex hormones and autonomic dysfunction in IBS.