Relevance in population surveys of study place and time to (i) the mean general population serum folate level, and (ii) the excess plasma homocysteine level in the TT versus CC <i>MTHFR</i> C677T genotype.

a<p>Mean folate levels average all who were surveyed; SE denotes the standard error due only to within-survey variation. Between-survey variation in folate levels is illustrated in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001177#pmed-1001177-g001" target="_blank">Figure 1</a>.</p>b<p>From inverse-variance-weighted averages of within-study differences in log homocysteine; <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001177#pmed.1001177.s001" target="_blank">Figure S1</a>, Table S2 in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001177#pmed.1001177.s006" target="_blank">Text S1</a>.</p>c<p>Mainly of Japanese, Chinese, or Korean populations; none of South Asians.</p

Effects of folic acid on major coronary events (nonfatal myocardial infarction or coronary death) in a meta-analysis of the published results of all large randomized trials of homocysteine reduction.

<p>Data for the VITATOPS trial are for myocardial infarction only. Data for FAVORIT are for all cardiovascular disease outcomes. Symbols and conventions as in <a href="http://www.plosmedicine.org/article/info:doi/10.1371/journal.pmed.1001177#pmed-1001177-g002" target="_blank">Figure 2</a>.</p

Homozygote CHD OR (TT versus CC <i>MTHFR</i> C677T genotype) in each probable folate status category, from meta-analyses of 86 published studies, 14 large (i.e., variance of log OR less than 0.05) and 72 smaller studies.

<p>Black squares indicate OR (with areas inversely proportional to the variance of log OR in each subdivision), and horizontal lines indicate 99% CIs. The overall OR and its 95% CI are indicated by a black diamond. Average homocysteine difference (in the non-CHD general population) for all areas and periods is weighted in proportion to the numbers of TT CHD cases in all 86 studies.</p

Mean serum folate concentrations in 81 population surveys, by calendar year and region.

<p>White squares, no folate supplementation; black squares, after folate supplementation; broken vertical line, 1995–1996, when folate supplementation began in the United States, Canada, Australia, New Zealand (US & ANZ), and some but not all European countries. No Asian surveys were in supplemented populations.</p

Homozygote CHD OR (TT versus CC <i>MTHFR</i> C677T genotype) in 19 unpublished datasets, yielding 24 parts that are classified by genotyping panel size.

<p>For these datasets, being unpublished introduces a negligible bias (less than 0.3% for each OR and about 0.1% for the overall OR: eAppendix 1). Black squares indicate OR (with areas inversely proportional to the variance of log OR), and horizontal lines indicate 99% CIs. The subtotals and their 99% CIs are indicated by black diamonds. The overall OR and its 95% CI is indicated by a white diamond. The weight (defined as the inverse of the variance of the maximum likelihood estimate of the log OR) and the product of the weight times OR indicates how much each study has contributed to the subtotals and totals. Because the weights and products are approximately additive, they can be used to estimate the effects of ignoring particular studies, or of grouping studies in different ways.</p