title: Quantitative trait loci for BMD identified by autosome-wide linkage scan to chromosomes 7q and 21q in men from the Amish Family Osteoporosis Study.
abstract: Using autosome-wide linkage analysis in 964 Amish, strong evidence was found for the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22 (LOD = 4.15 and 3.36, respectively).
  
  
  BACKGROUND
  BMD is highly heritable, with genetic factors accounting for 60-88% of variation. The goal of this study was to localize genes contributing to BMD variation.
  
  
  METHODS
  The Amish Family Osteoporosis Study was designed to identify genes affecting bone health. The Amish are a genetically closed population with a homogeneous lifestyle. BMD was measured at the spine, hip, and radius using DXA in 964 participants (mean age, 50.2 +/- 16.3 [SD] years; range, 18-99 years) from large multigenerational families. Genotyping of 731 highly polymorphic microsatellite markers (average spacing of 5.4 cM) and autosome-wide multipoint linkage analysis were performed.
  
  
  RESULTS
  In the overall study population, no strong evidence for linkage was detected to any chromosomal region (peak LOD: 2.11 for radius BMD on chromosome 3q26). In a subgroup analysis of men (n = 371), strong evidence was detected for a quantitative trait locus (QTL) influencing BMD variation on chromosome 7q31 at the total hip (LOD = 4.15) and femoral neck (LOD = 3.09) and for a second QTL influencing spine BMD at 21q22 (LOD = 3.36). Suggestive evidence of linkage was found in men for a QTL at 12q24 affecting total hip BMD (LOD = 2.60) and at 18p11 for femoral neck (LOD = 2.07), and in women (n = 593) at 1p36 for femoral neck BMD (LOD = 2.02) and at 1q21 for spine BMD (LOD = 2.11). In age subgroup analyses, suggestive evidence for linkage was found for those <50 years of age (n = 521) on chromosomes 11q22 and 14q23 (LODs = 2.11 and 2.16, respectively) and for those >50 years of age (n = 443) on 3p25.2 (LOD = 2.32).
  
  
  CONCLUSIONS
  These results strongly suggest the presence of genes affecting hip and spine BMD in men on chromosomes 7q31 and 21q22. Modest evidence was found for genes affecting BMD in women on chromosomes 1p36 and 1q21 and in men at 12q24, replicating results from other populations.
authors.affiliation: Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. estreete@medicine.umaryland.edu
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Streeten
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: McBride
authors.forename: Toni I
authors.initials: TI
authors.lastname: Pollin
authors.forename: Kathy
authors.initials: K
authors.lastname: Ryan
authors.forename: Jay
authors.initials: J
authors.lastname: Shapiro
authors.forename: Sandy
authors.initials: S
authors.lastname: Ott
authors.forename: Braxton D
authors.initials: BD
authors.lastname: Mitchell
authors.forename: Alan R
authors.initials: AR
authors.lastname: Shuldiner
authors.forename: Jeffery R
authors.initials: JR
authors.lastname: O'Connell
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D015519:Bone Density / Q000235:genetics*; D002874:Chromosome Mapping; D002891:Chromosomes, Human, Pair 21; D002897:Chromosomes, Human, Pair 7; D005260:Female; D008040:Genetic Linkage; D005828:Genetics, Population; D006801:Humans; D008126:Lod Score; D008297:Male; D008875:Middle Aged; D010024:Osteoporosis / Q000235:genetics*; D044382:Population Groups; D040641:Quantitative Trait Loci; D012307:Risk Factors