Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms:Application to Childhood Height

Combining genotype data across cohorts increases power to estimate the heritability due to common single nucleotide polymorphisms (SNPs), based on analyzing a Genetic Relationship Matrix (GRM). However, the combination of SNP data across multiple cohorts may lead to stratification, when for example, different genotyping platforms are used. In the current study, we address issues of combining SNP data from different cohorts, the Netherlands Twin Register (NTR) and the Generation R (GENR) study. Both cohorts include children of Northern European Dutch background (N = 3102 + 2826, respectively) w... Mehr ...

Verfasser: Fedko, Iryna O.
Hottenga, Jouke-Jan
Medina-Gomez, Carolina
Pappa, Irene
van Beijsterveldt, Catharina E. M.
Ehli, Erik A.
Davies, Gareth E.
Rivadeneira, Fernando
Tiemeier, Henning
Swertz, Morris A.
Middeldorp, Christel M.
Bartels, Meike
Boomsma, Dorret I.
Dokumenttyp: Artikel
Erscheinungsdatum: 2015
Reihe/Periodikum: Fedko , I O , Hottenga , J-J , Medina-Gomez , C , Pappa , I , van Beijsterveldt , C E M , Ehli , E A , Davies , G E , Rivadeneira , F , Tiemeier , H , Swertz , M A , Middeldorp , C M , Bartels , M & Boomsma , D I 2015 , ' Estimation of Genetic Relationships Between Individuals Across Cohorts and Platforms : Application to Childhood Height ' , Behavior Genetics , vol. 45 , no. 5 , pp. 514-528 . https://doi.org/10.1007/s10519-015-9725-7
Schlagwörter: Genotyping platform / Heterogeneity / Imputation / GCTA / SNP-heritability / Height / GENOME-WIDE ASSOCIATION / NETHERLANDS TWIN REGISTER / COMMON SNPS EXPLAIN / POPULATION-STRUCTURE / ADMIXED POPULATIONS / LARGE PROPORTION / GENERATION R / HERITABILITY / ARCHITECTURE
Sprache: Englisch
Permalink: https://search.fid-benelux.de/Record/base-27601062
Datenquelle: BASE; Originalkatalog
Powered By: BASE
Link(s) : https://hdl.handle.net/11370/7ca6982e-db78-425c-96ea-874a9f8146d6

Combining genotype data across cohorts increases power to estimate the heritability due to common single nucleotide polymorphisms (SNPs), based on analyzing a Genetic Relationship Matrix (GRM). However, the combination of SNP data across multiple cohorts may lead to stratification, when for example, different genotyping platforms are used. In the current study, we address issues of combining SNP data from different cohorts, the Netherlands Twin Register (NTR) and the Generation R (GENR) study. Both cohorts include children of Northern European Dutch background (N = 3102 + 2826, respectively) who were genotyped on different platforms. We explore imputation and phasing as a tool and compare three GRM-building strategies, when data from two cohorts are (1) just combined, (2) pre-combined and cross-platform imputed and (3) cross-platform imputed and post-combined. We test these three strategies with data on childhood height for unrelated individuals (N = 3124, average age 6.7 years) to explore their effect on SNP-heritability estimates and compare results to those obtained from the independent studies. All combination strategies result in SNP-heritability estimates with a standard error smaller than those of the independent studies. We did not observe significant difference in estimates of SNP-heritability based on various cross-platform imputed GRMs. SNP-heritability of childhood height was on average estimated as 0.50 (SE = 0.10). Introducing cohort as a covariate resulted in a parts per thousand 2 % drop. Principal components (PCs) adjustment resulted in SNP-heritability estimates of about 0.39 (SE = 0.11). Strikingly, we did not find significant difference between cross-platform imputed and combined GRMs. All estimates were significant regardless the use of PCs adjustment. Based on these analyses we conclude that imputation with a reference set helps to increase power to estimate SNP-heritability by combining cohorts of the same ethnicity genotyped on different platforms. However, important factors should be ...