Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications

A. Mesut Erzurumluoglu, Denis Baird, Tom G. Richardson, Nicholas J. Timpson, Santiago Rodriguez*

*Corresponding author for this work

Research output: Contribution to journalArticle (Academic Journal)peer-review

5 Citations (Scopus)
332 Downloads (Pure)


Y-chromosomal (Y-DNA) haplogroups are more widely used in population genetics than in genetic epidemiology, although associations between Y-DNA haplogroups and several traits, including cardiometabolic traits, have been reported. In apparently homogeneous populations defined by principal component analyses, there is still Y-DNA haplogroup variation which will result from population history. Therefore, hidden stratification and/or differential phenotypic effects by Y-DNA haplogroups could exist. To test this, we hypothesised that stratifying individuals according to their Y-DNA haplogroups before testing for associations between autosomal single nucleotide polymorphisms (SNPs) and phenotypes will yield difference in association. For proof of concept, we derived Y-DNA haplogroups from 6537 males from two epidemiological cohorts, Avon Longitudinal Study of Parents and Children (ALSPAC) (n = 5080; 816 Y-DNA SNPs) and the 1958 Birth Cohort (n = 1457; 1849 Y-DNA SNPs), and studied the robust associations between 32 SNPs and body mass index (BMI), including SNPs in or near Fat Mass and Obesity-associated protein (FTO) which yield the strongest effects. Overall, no association was replicated in both cohorts when Y-DNA haplogroups were considered and this suggests that, for BMI at least, there is little evidence of differences in phenotype or SNP association by Y-DNA structure. Further studies using other traits, phenome-wide association studies (PheWAS), other haplogroups and/or autosomal SNPs are required to test the generalisability and utility of this approach.

Original languageEnglish
Article number45
Number of pages11
Issue number1
Early online date22 Jan 2018
Publication statusPublished - Jan 2018

Bibliographical note

Special Issue: Complex Genetic Loci


  • 1958 Birth Cohort
  • Avon longitudinal study of parents and children
  • Body mass index
  • Haplogroups
  • Y-DNA


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