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

2 Citations (Scopus)
276 Downloads (Pure)

Abstract

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
JournalGenes
Volume9
Issue number1
Early online date22 Jan 2018
DOIs
Publication statusPublished - Jan 2018

Bibliographical note

Special Issue: Complex Genetic Loci

Keywords

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

Fingerprint Dive into the research topics of 'Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications'. Together they form a unique fingerprint.

Cite this