Linkage disequilibrium analysis in the genetically isolated Norfolk Island population

Bellis, Claire; Cox, Hannah; Ovcaric, Micky; Begley, Kimberly Nina; Lea, Rodney Arthur; Quinlan, Sharon Anne; Burgner, David; Heath, SC; Blangero, John; Griffiths, Lyn R.

doi:10.1038/sj.hdy.6801083

Cited by 25 publications

(21 citation statements)

References 54 publications

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“…A SOLAR LOD score of 3.0, 2.1, 1.2 and 0.59 equate to pointwise P values of 1×10 −4 , 1×10 −3 , 1×10 −2 , and 0.05, respectively. Previous studies of CVD risk determined the current trimmed pedigree structure had good power to detect the heritability of phenotypes whose variation is partially attributable to additive genetics and to detect loci for such phenotypes (Bellis et al, 2007). …”

Section: 1 Materials and Methodsmentioning

confidence: 99%

Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island

Cox

Lea

Bellis

et al. 2012

Gene

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Migraine is a common neurovascular disorder with a complex envirogenomic aetiology. In an effort to identify migraine susceptibility genes, we conducted a study of the isolated population of Norfolk Island, Australia. A large portion of the permanent inhabitants of Norfolk Island are descended from 18th Century English sailors involved in the infamous mutiny on the Bounty and their Polynesian consorts. In total, 600 subjects were recruited including a large pedigree of 377 individuals with lineage to the founders. All individuals were phenotyped for migraine using International Classification of Headache Disorders-II criterion. All subjects were genotyped for a genome-wide panel of microsatellite markers. Genotype and phenotype data for the pedigree was analyzed using heritability and linkage methods implemented in the program SOLAR. Follow-up association analysis was performed using the CLUMP program. A total of 154 migraine cases (25%) were identified indicating the Norfolk Island population is high-risk for migraine. Heritability estimation of the 377-member pedigree indicated a significant genetic component for migraine (h2=0.53, P=0.016). Linkage analysis showed peaks on chromosome 13q33.1 (P=0.003) and chromosome 9q22.32 (P=0.008). Association analysis of the key microsatellites in the remaining 223 unrelated Norfolk Island individuals showed evidence of association, which strengthen support for the linkage findings (P≤0.05). In conclusion, a genome-wide linkage analysis and follow-up association analysis of migraine in the genetic isolate of Norfolk Island provided evidence for migraine susceptibility loci on chromosomes 9q22.22 and 13q33.1.

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Section: 1 Materials and Methodsmentioning

confidence: 99%

Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island

Cox

Lea

Bellis

et al. 2012

Gene

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“…Consistent with their isolated history, we recently showed that a set of individuals drawn from Norfolk Island show long stretches of linkage disequilibrium. 19 Further background information on the Norfolk Island data 20 and on Polynesian settlement more generally 21 was published earlier.…”

Section: Introductionmentioning

confidence: 99%

Legacy of mutiny on the Bounty: founder effect and admixture on Norfolk Island

et al. 2009

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The population of Norfolk Island, located off the eastern coast of Australia, possesses an unusual and fascinating history. Most present-day islanders are related to a small number of the 'Bounty' mutineer founders. These founders consisted of Caucasian males and Polynesian females and led to an admixed present-day population. By examining a single large pedigree of 5742 individuals, spanning 4200 years, we analyzed the influence of admixture and founder effect on various cardiovascular disease (CVD)-related traits. On account of the relative isolation of the population, on average one-third of the genomes of present-day islanders (single large pedigree individuals) is derived from 17 initial founders. The proportion of Polynesian ancestry in the present-day individuals was found to significantly influence total triglycerides, body mass index, systolic blood pressure and diastolic blood pressure. For various cholesterol traits, the influence of ancestry was less marked but overall the direction of effect for all CVD-related traits was consistent with Polynesian ancestry conferring greater CVD risk. Marker-derived homozygosity was computed and agreed with measures of inbreeding derived from pedigree information. Founder effect (inbreeding and marker-derived homozygosity) significantly influenced height. In conclusion, both founder effect and extreme admixture have substantially influenced the genetic architecture of a variety of CVD-related traits in this population.

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“…Norfolk Island is a genetic isolate and has been targeted in previous genetic research into the aetiology of cardiovascular disease. [15][16][17] Using a similar approach, we are hoping to use this initial framework to uncover novel information about ocular phenotypes. Collectively, the population has been very supportive of health-related research.…”

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confidence: 99%

Distribution of conjunctival ultraviolet autoflourescence in a population-based study: the Norfolk Island Eye Study

Sherwin

Hewitt

Kearns

et al. 2011

Eye

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Objective The objective of this study was to describe the distribution of conjunctival ultraviolet autofluorescence (UVAF) in an adult population. Methods We conducted a cross-sectional, population-based study in the genetic isolate of Norfolk Island, South Pacific Ocean. In all, 641 people, aged 15 to 89 years, were recruited. UVAF and standard (control) photographs were taken of the nasal and temporal interpalpebral regions bilaterally. Differences between the groups for non-normally distributed continuous variables were assessed using the Wilcoxon-Mann-Whitney ranksum test. Trends across categories were assessed using Cuzick's non-parametric test for trend or Kendall's rank correlation s. Results Conjunctival UVAF is a nonparametric trait with a positively skewed distribution. Median amount of conjunctival UVAF per person (sum of four measurements; right nasal/temporal and left nasal/temporal) was 28.2 mm 2 (interquartile range 14.5-48.2). There was an inverse, linear relationship between UVAF and advancing age (Po0.001). Males had a higher sum of UVAF compared with females (34.4 mm 2 vs 23.2 mm 2 , Po0.0001). There were no statistically significant differences in area of UVAF between right and left eyes or between nasal and temporal regions. Conclusion We have provided the first quantifiable estimates of conjunctival UVAF in an adult population. Further data are required to provide information about the natural history of UVAF and to characterise other potential disease associations with UVAF. UVR protective strategies should be emphasised at an early age to prevent the long-term adverse effects on health associated with excess UVR.

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Linkage disequilibrium analysis in the genetically isolated Norfolk Island population

Cited by 25 publications

References 54 publications

Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island

Heritability and genome-wide linkage analysis of migraine in the genetic isolate of Norfolk Island

Legacy of mutiny on the Bounty: founder effect and admixture on Norfolk Island

Distribution of conjunctival ultraviolet autoflourescence in a population-based study: the Norfolk Island Eye Study

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