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Halldorsson, Bjarni V
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CitationJ. Bone Miner. Res. 2008, 23(10):1584-90
AbstractLow bone mass in adults is a major risk factor for low-impact fractures and is considered of complex origin because of interaction of environmental and genetic factors, each with modest effect. The objective was to assess the relative impact of genetics and environment and quantify the risk in relatives of osteopenic individuals. We studied 440 Icelandic nuclear families with 869 first-degree relatives of both sexes. Index cases (male or female) had BMD in the lumbar spine or hip >1.5 SD less than sex-matched controls. Heritability of BMD was estimated by maximum likelihood method, and variance component analysis was used to partition the genetic and environmental effects. Relative risk of low BMD (< -1 SD) in first-degree relatives was estimated, and heritable decrement in BMD was calculated compared with controls. Heritability was estimated as 0.61-0.66. Relative risk among first-degree relatives was 2.28, and the yield of screening was as high as 36%. The genetic influence was consistent with one or a few genes with considerable effect in addition to multiple genes each with a small effect. The genetic deficit in BMD was already present before 35 yr of age and equaled bone loss during 8-30 yr after menopause. We confirmed that genetics are more important than environment to low bone mass in adults. Our results are consistent with a few underlying genes with considerable effect. The prevalence among first-degree relatives of both sexes is common, suggesting that screening them should be cost effective and informative to elucidate the underlying genetics.
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