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

Genetic Epidemiology Group, Department of Health Sciences, University of Leicester, Leicester LE1 7RH, UK
MRC Integrative Epidemiology Unit (IEU), Population Health Sciences, Bristol Medical School, University of Bristol, Oakfield House, Oakfield Grove, Bristol BS8 2BN, UK
Author to whom correspondence should be addressed.
Genes 2018, 9(1), 45;
Received: 23 October 2017 / Revised: 16 January 2018 / Accepted: 16 January 2018 / Published: 22 January 2018
(This article belongs to the Special Issue Complex Genetic Loci)
PDF [1478 KB, uploaded 22 January 2018]


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. View Full-Text
Keywords: Y-DNA; haplogroups; body mass index; Avon Longitudinal Study of Parents and Children; 1958 Birth Cohort Y-DNA; haplogroups; body mass index; Avon Longitudinal Study of Parents and Children; 1958 Birth Cohort

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Erzurumluoglu, A.M.; Baird, D.; Richardson, T.G.; Timpson, N.J.; Rodriguez, S. Using Y-Chromosomal Haplogroups in Genetic Association Studies and Suggested Implications. Genes 2018, 9, 45.

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