AUTHOR=Ferwerda Bart , Abdellaoui Abdel , Nieuwdorp Max , Zwinderman Koos 

TITLE=A Genetic Map of the Modern Urban Society of Amsterdam

JOURNAL=Frontiers in Genetics

VOLUME=Volume 12 - 2021

YEAR=2021

URL=https://www.frontiersin.org/journals/genetics/articles/10.3389/fgene.2021.727269

DOI=10.3389/fgene.2021.727269

ISSN=1664-8021

ABSTRACT=Genetic differences between individuals underlie susceptibility for many diseases. Genome-wide association studies (GWAS) have discovered many susceptibility genes but were often limited to cohorts of predominantly European ancestry. Genetic diversity between individuals due to different ancestries and evolutionary histories show that this approach has limitations. In order to gain a better understanding of the associated genetic variation, we need a more global genomics approach including a greater diversity.
Here we introduce the Healthy Life in an Urban Setting (HELIUS) cohort. The HELIUS cohort consists of participants living in Amsterdam, with a level of diversity that reflects the Dutch colonial and recent migration past. The current study includes 10,283 participants with GWAS data available from seven groups of inhabitants namely; with a Dutch, African-Surinamese, South-Asian Surinamese, Turkish, Moroccan, Ghanaian and Javanese Surinamese background. First, we describe the genetic variation and admixture within the HELIUS cohort. Second, we show the challenges during imputation when having a genetically diverse cohort. Third, we conduct a body mass index (BMI) and height GWAS where we investigate the effects of a joint analysis of the entire cohort and a meta-analysis approach for the different sub-groups. Finally, we construct polygenic scores for BMI and height and compare their predictive power across the different ethnic groups.
Overall, we give a comprehensive overview of a genetically diverse cohort from Amsterdam. Our study emphasizes the importance of a less biased, more realistic, representation of urban populations for mapping genetic associations with complex traits and disease risk for all.