RESUMO
Irritable bowel syndrome (IBS) results from disordered brain-gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS with independent cohorts. We conducted a genome-wide association study with 53,400 cases and 433,201 controls and replicated significant associations in a 23andMe panel (205,252 cases and 1,384,055 controls). Our study identified and confirmed six genetic susceptibility loci for IBS. Implicated genes included NCAM1, CADM2, PHF2/FAM120A, DOCK9, CKAP2/TPTE2P3 and BAG6. The first four are associated with mood and anxiety disorders, expressed in the nervous system, or both. Mirroring this, we also found strong genome-wide correlation between the risk of IBS and anxiety, neuroticism and depression (rg > 0.5). Additional analyses suggested this arises due to shared pathogenic pathways rather than, for example, anxiety causing abdominal symptoms. Implicated mechanisms require further exploration to help understand the altered brain-gut interactions underlying IBS.
Assuntos
Transtornos de Ansiedade/genética , Síndrome do Intestino Irritável/genética , Transtornos do Humor/genética , Idoso , Antígeno CD56/genética , Moléculas de Adesão Celular/genética , Proteínas do Citoesqueleto/genética , Feminino , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Fatores de Troca do Nucleotídeo Guanina/genética , Proteínas de Homeodomínio/genética , Humanos , Síndrome do Intestino Irritável/epidemiologia , Masculino , Pessoa de Meia-Idade , Chaperonas Moleculares/genética , Polimorfismo de Nucleotídeo Único , Reino Unido/epidemiologiaRESUMO
A rapidly growing proportion of health research uses 'secondary data': data used for purposes other than those for which it was originally collected. Do researchers using secondary data have an obligation to disclose individual research findings to participants? While the importance of this question has been duly recognised in the context of primary research (ie, where data are collected from participants directly), it remains largely unexamined in the context of research using secondary data. In this paper, we critically examine the arguments for a moral obligation to disclose individual research findings in the context of primary research, to determine if they can be applied to secondary research. We conclude that they cannot. We then propose that the nature of the relationship between researchers and participants is what gives rise to particular moral obligations, including the obligation to disclose individual results. We argue that the relationship between researchers and participants in secondary research does not generate an obligation to disclose. However, we also argue that the biobanks or data archives which collect and provide access to secondary data may have such an obligation, depending on the nature of the relationship they establish with participants.
