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Biology subjects

Stamp, L. K.

Publications and source records attributed to Stamp, L. K..

2 recordsLinked to original sources

Discordant association of the CREBRF rs373863828 minor allele with increased body mass index and protection from type 2 diabetes in Maori and Pacific (Polynesian) people living in New Zealand

Aim/HypothesesThe minor allele of CREBRF rs373863828 associates with increased body mass index (BMI) and reduced risk of type 2 diabetes (T2D) in the Samoan population of Samoa and American Samoa. Our aim was to test rs373863828 for association with BMI and odds of T2D, gout and chronic kidney disease (CKD) in M[a]ori and Pacific (Polynesian) people living in Aotearoa New Zealand in 2,286 adults.\n\nMethodsAssociation analyses were performed by linear and logistic regression with BMI, log-transformed BMI, waist circumference, T2D, gout and CKD. Analyses were adjusted for age, sex, the first four genome-wide principal components, and (when appropriate) BMI, waist circumference and T2D.\n\nResultsFor the minor allele of rs373863828 the effect size for log-transformed BMI was 0.038 (95% CI [0.022-0.055], P=4.8x10-6) and for T2D was OR=0.59 (95% CI [0.47-0.73], P=1.9x10-6). There was no evidence for association of genotype with variance in BMI (P=0.13). Nor was there evidence for association with serum urate ({beta}=0.012 mmol/L, Pc=0.10), gout (OR=1.00, P=0.98) or CKD (OR=0.91, P=0.59).\n\nConclusions/interpretationOur results replicated, with very similar effect sizes, association of the minor allele of rs373863828 with higher BMI but lower odds of T2D among New Zealand Polynesian adults, as in Samoan adults living in Samoa and American Samoa.

genetics

Multiplexed nanopore sequencing of HLA-B locus in Maori and Polynesian samples

The human leukocyte antigen (HLA) system is a gene family that encodes the human major histocompatibility complex (MHC). HLA-B is the most polymorphic gene in the MHC class I region, comprised of 4,765 HLA-B alleles (IPD-IMGT/HLA Database Release 3.28). Many HLA-B alleles have been associated with adverse drug reactions and disease risks, and we are interested in developing efficient methods for analysis of HLA alleles in this context. Here we describe an approach to HLA-B typing using multiplexed next generation sequencing on the MinION nanopore sequencer (Oxford Nanopore Technologies), combined with data analysis with the SeqNext-HLA software package (JSI Medical Systems GmbH, Ettenheim, Germany). The nanopore sequencer offers the advantages of long-read capability and single molecule reads, which can facilitate effective haplotyping. We developed this method using reference samples of known HLA-B type as well as individuals of New Zealand M[a]ori or Pacific Island (Polynesian) descent, because HLA-B diversity in these populations is not well understood. We demonstrate here that nanopore sequencing of barcoded, pooled, 943 bp polymerase chain reaction (PCR) amplicons of 49 DNA samples, on one R9.4 flowcell (Oxford Nanopore Technologies), generated ample read depth for all samples. Sequence analysis using SeqNext-HLA software assigned HLA-B alleles to all samples at high-resolution with very little ambiguity. Our PCR-based next generation sequencing method is a scaleable and efficient approach for genotyping HLA-B and potentially any other HLA locus. Finally, we report our findings on HLA-B genotypes of this cohort, which adds to our understanding of HLA-B allele frequencies among M[a]ori and Polynesian people.

genetics