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"Hole, David J"
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Population Structure and Linkage Disequilibrium in U.S. Barley Germplasm: Implications for Association Mapping
Previous studies have shown that there is considerable population structure in cultivated barley (Hordeum vulgare L.), with the strongest structure corresponding to differences in row number and growth habit. U.S. barley breeding programs include six-row and two-row types and winter and spring types in all combinations. To facilitate mapping of complex traits in breeding germplasm, 1816 barley lines from 10 U.S. breeding programs were scored with 1536 single nucleotide polymorphism (SNP) genotyping assays. The number of SNPs segregating within breeding programs varied from 854 to 1398. Model-based analysis of population structure showed the expected clustering by row type and growth habit; however, there was additional structure, some of which corresponded to the breeding programs. The model that fit the data best had seven populations: three two-row spring, two six-row spring, and two six-row winter. Average linkage disequilibrium (LD) within populations decayed over a distance of 20 to 30 cM, but some populations showed long-range LD suggestive of admixture. Genetic distance (allele-sharing) between populations varied from 0.11 (six-row spring vs. six-row spring) to 0.45 (two-row spring vs. six-row spring). Analyses of pairwise LD revealed that the phase of allelic associations was not well correlated between populations, particularly when their allele-sharing distance was >0.2. These results suggest that pooling divergent barley populations for purposes of association mapping may be inadvisable.
Journal Article
Quantitative Trait Loci Associated with the Tocochromanol (Vitamin E) Pathway in Barley
The Genome-Wide Association Studies approach was used to detect Quantitative Trait Loci associated with tocochromanol concentrations using a panel of 1,466 barley accessions. All major tocochromanol types- α-, β-, δ-, γ-tocopherol and tocotrienol- were assayed. We found 13 single nucleotide polymorphisms associated with the concentration of one or more of these tocochromanol forms in barley, seven of which were within 2 cM of sequences homologous to cloned genes associated with tocochromanol production in barley and/or other plants. These associations confirmed a prior report based on bi-parental QTL mapping. This knowledge will aid future efforts to better understand the role of tocochromanols in barley, with specific reference to abiotic stress resistance. It will also be useful in developing barley varieties with higher tocochromanol concentrations, although at current recommended daily consumption amounts, barley would not be an effective sole source of vitamin E. However, it could be an important contributor in the context of whole grains in a balanced diet.
Journal Article
Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer?
Previous studies have reported an increased risk of cancer with calcium-channel blockers in man. Other work in animals suggests that inhibitors of angiotensin-l-converting enzyme (ACE) protect against cancer. We aimed to assess the risk of cancer in hypertensive patients receiving ACE inhibitors or other antihypertensive drugs.
Our retrospective cohort study was based on the records of 5207 patients who attended the Glasgow Blood Pressure Clinic between Jan 1, 1980, and Dec 31, 1995. The patients' records are linked with the Registrar General Scotland and the West of Scotland Cancer Registry.
Compared with the West of Scotland controls, the relative risks of incident and fatal cancer among the 1559 patients receiving ACE inhibitors were 0·72 (95% Cl 0·55–0·92) and 0·65 (0·44–0·93). Among the 3648 patients receiving antihypertensive drugs other than ACE inhibitors (calcium-channel blockers 1416, diuretics 2099, β-blockers 2681), the corresponding relative risks were 1·10 (0·97–1·22) and 1·03 (0·87–1·20). The relative risk of cancer was lowest in women on ACE inhibitors: 0·63 (0·41–0·93) for incident cancer; 0·48 (0·23–0·88) for fatal cancer; and 0·37 (0·12–0·87) for female-specific cancers. The reduced relative risk of cancer in patients on ACE inhibitors was greatest with follow-up of longer than 3 years. Calcium-channel blockers, diuretics, and β-blockers had no apparent effect on risk of cancer.
Long-term use of ACE inhibitors may protect against cancer. The status of this finding is more that of hypothesis generation than of hypothesis testing; randomised controlled trials are needed.
Journal Article
Incidence of and survival from malignant melanoma in Scotland: an epidemiological study
We aimed to assess the incidence and survival for all patients with invasive primary cutaneous malignant melanoma diagnosed in Scotland, UK, during 1979–98.
The Scottish Melanoma Group obtained data for 8830 patients (3301 male and 5529 female) first diagnosed with invasive cutaneous malignant melanoma.
Age-standardised incidence rose from 3·5 in 1979 to 10·6 per 10
5
population in 1998 for men, and from 7·0 to 13·1 for women, a rise of 303% and 187%, respectively. After 1995, the rate of increase levelled in women younger than 65 years at diagnosis. Melanoma incidence increased most in men on the trunk, head, and neck and in women on the leg. 5-year survival rose from 58% to 80% for men diagnosed in 1979 and 1993, respectively, and from 74% to 85% for women; improvements of 38% (p<0·001) and 15% (p<0·001), respectively. Most improvement was attributable to a higher proportion of thinner tumours. Male mortality from melanoma was 1·9/10
5
population per year at the start and end of the study, whereas mortality for men younger than 65 years at diagnosis rose from 1·2 to 1·35 (p=0·24). For all women, mortality fell slightly from 1·9 to 1·85/10
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population per year (p=0·61), whereas for women younger than 65 years at diagnosis, mortality fell from 1·3 to 1·15 (p=0·62).
Interventions aimed at both primary and secondary prevention of melanoma are justified. Specialist tumour registers for entire countries can be used to plan and monitor public health interventions.
Published online June 25, 2002. http://image.thelancet.com/extras/01art7335web.pdf
Journal Article
Effect of conjugal bereavement on mortality of the bereaved spouse in participants of the Renfrew/Paisley Study
Objectives: To investigate how loss of a spouse affects mortality risk in the bereaved partner. Design and setting: Prospective cohort study in Renfrew and Paisley in Scotland. Participants: 4395 married couples aged 45–64 years when the study was carried out between 1972 and 1976. Methods: The date of bereavement for the bereaved spouse was the date of death of his or her spouse. Bereavement could occur at any time during the follow-up period, so it was considered as a time-dependent exposure variable and the Cox proportional hazards model for time-dependent variables was used. The relative rate (RR) of mortality was calculated for bereaved versus non-bereaved spouses and adjusted for confounding variables. Main outcome measures: Causes of death to 31 March 2004. Results: Bereaved participants were at higher risk than non-bereaved participants of dying from any cause (RR 1.27; 95% CI 1.2 to 1.35). These risks remained but were attenuated after adjustment for confounding variables. There were raised RRs for bereaved participants dying of cardiovascular disease, coronary heart disease, stroke, all cancer, lung cancer, smoking-related cancer, and accidents or violence. After adjustment for confounding variables, RRs remained higher for bereaved participants for all these causes except for mortality from lung cancer. There was no strong statistical evidence that the increased risks of death associated with bereavement changed with time after bereavement. Conclusions: Conjugal bereavement, in addition to existing risk factors, is related to mortality risk for major causes of death.
Journal Article
Alcohol consumption and mortality from all causes, coronary heart disease, and stroke: results from a prospective cohort study of Scottish men with 21 years of follow up
Abstract Objectives: To relate alcohol consumption to mortality. Design: Prospective cohort study. Setting: 27 workplaces in the west of Scotland. Participants: 5766 men aged 35-64 when screened in 1970-3 who answered questions on their usual weekly alcohol consumption. Main outcome measures: Mortality from all causes, coronary heart disease, stroke, and alcohol related causes over 21 years of follow up related to units of alcohol consumed per week. Results: Risk for all cause mortality was similar for non-drinkers and men drinking up to 14 units a week. Mortality risk then showed a graded association with alcohol consumption (relative rate compared with non-drinkers 1.34 (95% confidence interval 1.14 to 1.58) for 15-21 units a week, 1.49 (1.27 to 1.75) for 22-34 units, 1.74 (1.47 to 2.06) for 35 or more units). Adjustment for risk factors attenuated the increased relative risks, but they remained significantly above 1 for men drinking 22 or more units a week. There was no strong relation between alcohol consumption and mortality from coronary heart disease after adjustment. A strong positive relation was seen between alcohol consumption and risk of mortality from stroke, with men drinking 35 or more units having double the risk of non-drinkers, even after adjustment. Conclusions: The overall association between alcohol consumption and mortality is unfavourable for men drinking over 22 units a week, and there is no clear evidence of any protective effect for men drinking less than this.
Journal Article
Survival outcome of care by specialist surgeons in breast cancer: a study of 3786 patients in the west of Scotland
Abstract Objective: To compare survival outcome for patients with breast cancer cared for by specialist and non-specialist surgeons in a geographically defined area. Design: Retrospective study of all female patients aged under 75 years in the area treated between 1980 and June 1988 (before breast screening began). Patients were identified from the cancer registry and from pathology records of all hospitals in the area. Specialist surgeons were identified by one author. All other surgeons caring for patients from the area were considered non-specialists. Setting: A geographically defined population in urban west of Scotland. Subjects: 3786 patients with histologically verified breast cancer operated on between 1 January 1980 and 30 June 1988 and followed to 31 December 1993. Main outcome measures: Five and 10 year survival rates for specialists and non-specialists; relative hazard ratios derived from Cox's proportional hazards model adjusted for prognostic factors—age, socioeconomic status, tumour size, and nodal involvement. Results: The five year survival rate was 9% higher and the 10 year survival 8% higher for patients cared for by specialist surgeons. A reduction in risk of dying of 16% (95% confidence interval 6% to 25%) was found after adjustment for age, tumour size, socioeconomic status, and nodal involvement. The benefit of specialist care was apparent for all age groups, for small and large tumours, and for tumours that did and did not affect the nodes and was consistent across all socioeconomic categories. Conclusions: Survival differences of the magnitude demonstrated have implications for the provision of services for the treatment of women with breast cancer. There is a need to improve equity in the treatment of breast cancer.
Journal Article
Body mass index in middle life and future risk of hospital admission for psychoses or depression: findings from the Renfrew/Paisley study
There is evidence that greater body mass index (BMI) protects against depression, schizophrenia and suicide. However, there is a need for prospective studies.
We examined the association of BMI with future hospital admissions for psychoses or depression/anxiety disorders in a large prospective study of 7036 men and 8327 women. Weight and height were measured at baseline (1972-76) when participants were aged 45-64. Follow-up was for a median of 29 years.
Greater BMI and obesity were associated with a reduced risk of hospital admission for psychoses and depression/anxiety in both genders, with the magnitude of these associations being the same for males and females. With adjustment for age, sex, smoking and social class, a 1 standard deviation (s.d.) greater BMI at baseline was associated with a rate ratio of 0.91 [95% confidence interval (CI) 0.82-1.01] for psychoses and 0.87 (95% CI 0.77-0.98) for depression/anxiety. Further adjustment for baseline psychological distress and total cholesterol did not alter these associations.
Our findings add to the growing body of evidence that suggests that greater BMI is associated with a reduced risk of major psychiatric outcomes. Long-term follow-up of participants in randomized controlled trials of interventions that effectively result in weight loss and the use of genetic variants that are functionally related to obesity as instrumental variables could help to elucidate whether these associations are causal.
Journal Article
Economically Optimal Compost Rates for Organic Crop Production
Current guidelines for the use of compost in organic agriculture are based on nutrient targets, which represent the conditions needed for maximum yield. Due to the high cost of inputs, however, a maximum-yield strategy may be far from economically optimal in some organic cropping systems. In this article we formulate a theory of economically optimal rates (EORs) for compost that incorporates the effects on yield in the years after application. When carryover is neglected, it is well known that the slope of the yield response at the EOR equals the fertilizer/crop price ratio. We show that when carry-over effects are modeled with a decay series, the critical slope is reduced by the sum of the decay series, and this criterion holds for each crop in a rotation. To demonstrate the application of these theoretical results, we used data from a previous study in which the dryland wheat yield response to compost was measured on organic farmland in northern Utah. Since a decay series was not measured, EORs are presented for a range of values of the cumulative carryover, as well as for different compost/wheat price ratios. The EOR for compost sold by one of the region's main composting facilities was predicted to be zero, which highlights the challenging nature of organic fertility management in northern Utah's dryland agriculture. Confidence in the EOR was hindered by our limited understanding of carryover in dryland systems, which should be a priority for future research.
Journal Article