Fine-scale population structure and demographic history of British Pakistanis

Arciero, Elena; Dogra, Sufyan Abid; Mezzavilla, Massimo; Tsismentzoglou, Theofanis; Huang, Qin Qin; Hunt, Karen A.; Mason, Dan; Heel, David A. van; Sheridan, Eamonn; Wright, John; Small, Neil; Carmi, Shai; Iles, Mark M.; Martin, Hilary C.

doi:10.1101/2020.09.02.279190

Cited by 11 publications

(15 citation statements)

References 107 publications

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“…Ethnicity was self-reported and the homogeneity of the WE group has been confirmed in previous genetic analyses within BIB (33). 93.2% of the included WEs were born in the British Isles (i.e., the UK, Republic of Ireland, Channel Islands or Isle of Man), with the majority in England (91.4%).…”

Section: Methodsmentioning

confidence: 68%

Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low and High-Risk Women Living in the UK

Fuller

Iles

Moore

et al. 2022

Preprint

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Background: Gestational Diabetes Mellitus (GDM) is the most common pregnancy complication to occur worldwide, however prevalence varies substantially between ethnicities with South Asians experiencing up to 3-times the risk of the disease compared to white Europeans (WEs). Factors driving this discrepancy in prevalence and the pathogenesis of GDM are unclear, although the metabolome is of great importance due to the metabolic dysregulation characterised GDM. Objective: To characterise and distinguish the metabolic profiles of GDM in two distinct ethnic populations at < 28 weeks gestation. Design: 146 fasting serum metabolite values, quantified by nuclear magnetic resonance, from 2668 pregnant WE and 2671 pregnant Pakistani (PK) women from the Born in Bradford (BIB) cohort, were analysed using partial least squares discriminatory analyses (PLSDA). The presence of a linear relationships between metabolite values and post-oral glucose tolerance test measures of dysglycemia (fasting glucose and 2- hour post glucose) were also examined. Results: Seven metabolites were associated with GDM status in both ethnicities, while 6 additional metabolites associated with GDM only in WE women. Unique metabolic profiles were observed in healthy weight women who later developed GDM, with distinct metabolite patterns identified by ethnicity and BMI status. Of the 146 metabolite values analysed in relation to dysglycemia, quantities of lactate, histidine, apolipoprotein A1, HDL cholesterol, HDL2 cholesterol, and DHA, as well as the diameter of very low density lipoprotein particles (nm) were associated with dysglycemia in WE women; while in PK women albumin alone associated with dysglycemia. Conclusion: This is the first study to show that the metabolic risk profile for GDM differs between ethnicities and highlights a need for ethnically appropriate GDM prevention strategies.

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Section: Methodsmentioning

confidence: 68%

Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low and High-Risk Women Living in the UK

Fuller

Iles

Moore

et al. 2022

Preprint

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“…S9b). A notable feature of the XSA cohort is elevated genomic inbreeding, likely due to endogamy 45 , particularly among self-identified Pakistanis 46 (Fig. S9a).…”

Section: Resultsmentioning

confidence: 99%

The sequences of 150,119 genomes in the UK biobank

Halldórsson

Moore

Hauswedell

et al. 2021

Preprint

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We describe the analysis of whole genome sequencing (WGS) of 150,119 individuals from the UK biobank (UKB). This yielded a set of high quality variants, including 585,040,410 SNPs, representing 7.0% of all possible human SNPs, and 58,707,036 indels. The large set of variants allows us to characterize selection based on sequence variation within a population through a Depletion Rank (DR) score for windows along the genome. DR analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UKB, a large British Irish cohort (XBI) and smaller African (XAF) and South Asian (XSA) cohorts. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large scale WGS studies. Using this formidable new resource, we provide several noteworthy examples of trait associations with rare variants with large effects not found previously through studies based on exome sequencing and/or imputation.

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“…Because we have found that the different types of first-cousin consanguinity generate an observable effect on X chromosomal coalescence times, it is possible that features of coalescence times can be compared across populations to assess signatures of the different types of consanguinity. Such assessments can potentially capitalize on the inverse relationship between coalescence times and genomic sharing (Palamara et al ., 2012; Carmi et al ., 2014; Browning and Browning, 2015) to use genomic sharing patterns to uncover features of consanguinity (Arciero et al ., 2021).…”

Section: Discussionmentioning

confidence: 99%

Limiting distribution of X-chromosomal coalescence times under first-cousin consanguineous mating

Cotter¹,

Severson²,

Carmi

et al. 2022

Preprint

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By providing additional opportunities for coalescence within families, the presence of consanguineous unions in a population reduces coalescence times relative to non-consanguineous populations. First-cousin consanguinity can take one of six forms differing in the configuration of sexes in the pedigree of the male and female cousins who join in a consanguineous union: patrilateral parallel, patrilateral cross, matrilateral parallel, matrilateral cross, bilateral parallel, and bilateral cross. Considering populations with each of the six types of first-cousin consanguinity individually and a population with a mixture of the four unilateral types, we examine coalescent models of consanguinity. We previously computed, for first-cousin consanguinity models, the mean coalescence time for X-chromosomal loci and the limiting distribution of coalescence times for autosomal loci. Here, we use the separation-of-time-scales approach to obtain the limiting distribution of coalescence times for X-chromosomal loci. This limiting distribution has an instantaneous coalescence probability that depends on the probability that a union is consanguineous; lineages that do not coalesce instantaneously coalesce according to an exponential distribution. We study the effects on the coalescence time distribution of the type of first-cousin consanguinity, showing that patrilateral-parallel and patrilateral-cross consanguinity have no effect on X-chromosomal coalescence time distributions and that matrilateral-parallel consanguinity decreases coalescence times to a greater extent than does matrilateral-cross consanguinity.

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Fine-scale population structure and demographic history of British Pakistanis

Cited by 11 publications

References 107 publications

Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low and High-Risk Women Living in the UK

Unique Metabolic Profiles Associate with Gestational Diabetes and Ethnicity in Low and High-Risk Women Living in the UK

The sequences of 150,119 genomes in the UK biobank

Limiting distribution of X-chromosomal coalescence times under first-cousin consanguineous mating

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