Background and aims: Diverticular disease is among the most prevalent conditions encountered by gastroenterologists, affecting ~50% of Americans before the age of 60. Our aim was to identify genetic risk variants and clinical phenotypes associated with diverticular disease, utilizing the electronic health record (EHR) with Natural Language Processing (NLP). Methods: We developed a NLP-enriched phenotype algorithm that incorporated colonoscopy or abdominal imaging reports to accurately identify patients with diverticulosis and diverticulitis from multicenter EHRs. We performed genome-wide association studies (GWAS) of diverticular disease in European, African and multi-ancestry participants, followed by phenome-wide association studies (PheWAS) of the risk variants to identify their potential comorbid/pleiotropic effects in the clinical phenome. For more in-depth investigation of associated clinical phenotypes, we also performed PheWAS with the previously reported 52 GWAS susceptibility variants for diverticular disease. Results: Ancestry-stratified GWAS analyses confirmed the well-established associations between ARHGAP15 loci with diverticular disease in European cohorts, and found similar positive effect sizes in African cohorts but with non-significant p-values. With overall intensified GWAS signals in diverticulitis patients compared to diverticulosis patients, we found substantial genetic correlations between diverticulosis and diverticulitis, up to 0.997 in European ancestry. PheWAS analyses identified associations between the diverticular disease GWAS variants and circulatory system, genitourinary, and neoplastic EHR phenotypes. Conclusion: Our multiancestry GWAS-PheWAS study demonstrated an effective use of multidimensional EHR information in disease case/control classification with NLP for more comprehensive and scalable phenotyping, and implementation of an integrative analytical pipeline to facilitate etiological investigation of a disease from a clinical perspective. ### Competing Interest Statement The authors have declared no competing interest.

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