TY - JOUR
T1 - A Genetic Map of the Modern Urban Society of Amsterdam
AU - Ferwerda, Bart
AU - Abdellaoui, Abdel
AU - Nieuwdorp, Max
AU - Zwinderman, Koos
N1 - Funding Information: The Amsterdam University Medical Centers—AMC and the Public Health Service of Amsterdam (GGD Amsterdam)— provided core financial support for HELIUS. The HELIUS study is also funded by the research grants of the Dutch Heart Foundation (Hartstichting; grant no. 2010T084), the Netherlands Organization for Health Research and Development (ZonMw; grant no. 200500003), the European Integration Fund (EIF; grant no. 2013EIF013), and the European Union (Seventh Framework Programme, FP-7; grant no. 278901). MN is supported by a ZonMw VICI grant 2020. AA is supported by the Foundation Volksbond Rotterdam and by ZonMw grant 849200011 from the Netherlands Organization for Health Research and Development. Publisher Copyright: Copyright © 2021 Ferwerda, Abdellaoui, Nieuwdorp and Zwinderman.
PY - 2021/11/30
Y1 - 2021/11/30
N2 - Genetic differences between individuals underlie susceptibility to 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 shows 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 genetic data available from seven groups of inhabitants, namely, Dutch, African Surinamese, South-Asian Surinamese, Turkish, Moroccan, Ghanaian, and Javanese Surinamese. 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 subgroups. 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 and more realistic representation of urban populations for mapping genetic associations with complex traits and disease risk for all.
AB - Genetic differences between individuals underlie susceptibility to 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 shows 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 genetic data available from seven groups of inhabitants, namely, Dutch, African Surinamese, South-Asian Surinamese, Turkish, Moroccan, Ghanaian, and Javanese Surinamese. 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 subgroups. 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 and more realistic representation of urban populations for mapping genetic associations with complex traits and disease risk for all.
KW - GWAS
KW - HELIUS
KW - admixture
KW - genetics
KW - multiethnic cohort
UR - http://www.scopus.com/inward/record.url?scp=85121352601&partnerID=8YFLogxK
U2 - https://doi.org/10.3389/fgene.2021.727269
DO - https://doi.org/10.3389/fgene.2021.727269
M3 - Article
C2 - 34917125
SN - 1664-8021
VL - 12
JO - Frontiers in genetics
JF - Frontiers in genetics
M1 - 727269
ER -