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Detection of QTL in outbred half-sib family structures has mainly been based on interval mapping of single QTL on individual chromosomes. Methods to account for linked and unlinked QTL have been developed, but most of them are only applicable in designs with inbred species or pose great demands on computing facilities. This study describes a strategy that allows for rapid analysis, involving multiple QTL, of complete genomes. The methods combine information from individual analyses after which trait scores for a specific linkage group are adjusted for identified QTL at other linkage groups. Regression methods are used to estimate QTL positions and effects; permutation tests are used to obtain empirical threshold values. The description of the methods is complemented by an example of the combined analysis of 28 bovine chromosomes and their associations with milk yield in Finnish Ayrshire cattle. In this example, the individual analysis revealed five suggestive QTL affecting milk yield. Following the strategy presented in this paper, the final combined analysis showed eight significant QTL affecting milk yield. This clearly demonstrates the potential gain of using the combined analysis. The use of regression methods, with low demands on computing resources, makes this approach very practical for total genome scans.

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Growth hormone receptor (GHR) has a major role in the regulation of growth hormone action, and thus, is an obvious candidate gene associated with milk production traits in mammals. The present authors have sequenced 273 bp of the 3' flanking region of the bovine GHR, and found three length variants and one base substitution polymorphism in this region. Allele frequencies of the length variants differ between Finnish native and commercial dairy cattle breeds. The chromosomal localization of GHR was confirmed to bovine chromosome 20 by synteny mapping and linkage analysis.

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The North Karelia Project is a community-based program to reduce the high cardiovascular disease rates in the province of North Karelia in eastern Finland. Dietary changes aimed at reducing serum cholesterol levels were among the main objectives. The evaluation of the program was based on examinations of independent cross-sectional population samples in 1972, 1977, and 1982 in North Karelia and in a matched reference area. A questionnaire was used to measure changes in dietary habits during the program. A major shift from whole to low-fat milk took place in both areas as well as a reduction in the amount of butter used on bread. The net reduction in North Karelia (difference in change compared with the reference area) in the intake of saturated fatty acids from milk and fat spreads used on bread was 20% in men and 14% in women. This reduction was similar in different age, education, and occupational groups suggesting that the dietary intervention had reached the whole community. The validity of the reported dietary changes was confirmed by parallel changes in serum cholesterol levels.

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The North Karelia Worksite Intervention Study was carried out to assess the effectiveness of worksite-based innovative intervention on chronic disease risk factors. The one-year intervention combined use of mass media, worksite opinion leaders, risk assessment and counselling and other health education measures. The study used eight medium sized intervention worksites (IW) and eight matched reference worksites (RW). Of the 715 workers 91% participated in the initial survey, and out of these 89% in the one-year follow-up survey. The proportion of current smokers changed from 39% to 30% (p less than 0.05) at the IWs while no change took place at the RWs (33%). The effect on smoking was confirmed by serum thiocyanate analyses. An additive score of the three main CHD risk factors changed from 3.1 to 2.7 at the IWs and from 3.2 to 3.0 at the RWs (p less than 0.05 for the net change). The results and experiences showed the feasibility of the intervention and significant, although modest, effects on risk factors and health behaviour, notably smoking.

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PIP: This article describes the systematic use of lay opinion leaders in the North Karelia project, a comprehensive community-based preventive cardiovascular program in Finland. Over 800 lay opinion leaders were trained to promote the reduction of heart disease risk factors and, after approximately 4 years, a survey was conducted to assess the long-term feasibility and self-reported effects. 267 of the 399 active lay workers surveyed were women; their median age was 52 years. The median age of the men was 50. 86% of the lay workers were married, and the majority lived in large villages. On the average they were members of 4 different associations or organizations and had acted as lay health workers for an average of 4 years. About 10% of these workers stated that they had had coronary heart disease themselves, and hypertension had been diagnosed in 19%. Only 2% were current smokers. The different types of milk they consumed was 1 indicator of their dietary habits: 14% too no milk at all, 23% skim milk/butter milk, 27% "low-fat" milk, 13% "consumption" milk (fatty milk), and 23% "full milk" (directly from the farm). 78% said they used butter on their bread. According to the lay workers' findings, 15% responded "very positively" and 60% "positively" in discussions about health matters; only 1% were reported as negative. There was little difference between the answers given by male and female lay workers. Discussions about physical activity were said to be the easiest, all other topics being only relatively easy. Although changes in health behavior were important, these workers saw clearly the difficulties in influencing people to accomplish these changes. Altogether 36% of the lay workers reported that at least 1 person had stopped smoking in association with their efforts, and 3% reported that as many as 6 or more persons had stopped smoking. This means that over 500 persons had over this period of time been influenced by the program to stop smoking. About 15-25% of the lay workers tried to promote action to restrict smoking in local bars, worksites, and at local meeting places. In bars this was rarely successful but in the other places some change often followed. The overall community impact of this volunteer lay worker activity cannot be assessed with certainty, but the overall evaluation of the project interventions in North Karelia from 1972-82 showed a major impact on behaviors and risk factors related to cardiovascular disease, i.e., a 28% reduction in smoking when adjusted for simultaneous changes in a matched reference area and a significant reduction in coronary mortality rates in contrast to the rest of the country.^ieng

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A dietary intervention study to reduce risk factors for coronary heart disease was carried out among 30 free-living middle-aged couples in North Karelia, Eastern Finland. During the study, the subjects changed their normal diet for six weeks. The main changes in the diet were decrease in the consumption of fat (from 39% to 24% of total calories), increase in the P:S ratio from 0.15 to 1.22, and increased consumption of fruit and vegetables. The changes in the food consumption pattern were facilitated by giving the families free food items, such as skim milk, vegetable margarine, vegetables, and fruit. The food consumption and nutrient intakes were measured by food consumption records kept every other day. Also, duplicate diets were collected once during each study period for chemical analysis. Compliance with the dietary changes was better than expected, and the acceptability and the palatability of the diet were reported to be good. The decrease in the fat content of the diet increased the nutrient density of the diet; i.e., the concentration of vitamins and minerals improved. This study showed how even more drastic dietary changes than those recommended by health authorities can be realized among ordinary Finnish people.

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Thirty couples living in Liperi, a community of North Karelia, aged 40 to 50 yr participated in a dietary intervention study to assess the influence of dietary fat on blood pressure and other parameters. After a weeklong base-line period the subjects consumed a low fat diet (24% of energy) with a polyunsaturated/saturated fat ratio (P/S) of 1.2 for 6 wk. After this 6-wk intervention period the subjects resumed their normal diets (36% energy from fat, P/S 0.15) for an additional 6-wk period. Body weight remained constant throughout the study and salt intakes were approximately 12 g/day. During the low fat, high P/S period a decrease of 7.5 and 2.8 mm Hg pressure occurred for systolic and diastolic blood pressure from the base-line level. When the normal diet was resumed, systolic and diastolic blood pressures increased by 7.7 and 6.3 mm Hg, respectively, from the levels observed at the end of the intervention period.

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57 couples living in two communities of North Karelia, aged 30-50 years, were randomly allocated to three groups. After a 2-week baseline period group I followed a diet low in fat (23% of energy) with a high polyunsaturated/saturated (P/S) ratio (1 . 0), group II reduced daily salt intake from 192 mmol to 77 mmol, and group III (control group) continued the usual diet. After the 6-week intervention period groups I and II reverted to their usual diets. In group I systolic blood pressure declined from 138 . 4 to 129 . 5 mm Hg and diastolic blood pressure from 88 . 9 to 81 . 3 mm Hg during the intervention period; the values rose during switch-back. The fall was greater among hypertensive than among normotensive subjects. In groups II and III the mean blood pressure changed very little during the study.

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