Meyerhof family graves; Jewish cemetery; Hildesheim Cemeteries Tombs

(l-r) Ilse Meyerhof, Joel Meyerhof (father), Adolf Meyerhof

Portrait of Yael Bernkopf with her grandmother Aenny Catzenstein nee Gottschalk; Israel Portraits Family

Digital Image

Margot Molling with her brother Adolf Molling; Laughlin, Nevada Portraits Family

Temperature: 117 F

Patrick and Susan Matthiesen playing chess at Aenny Catzenstein nee Gottschalk's 80th birthday; London Portraits Family

Digital Image

Family and guests at Aenny Catzenstein nee Gottschalk's 80th birthday; London.

Front row l-r: Beatrice Durand, Francine Durand and Aenny Catzenstein, the boys are Ara-Serge Donabedian and Patrick Matthiesen and the adults are Susan Prior, Francis Matthiesen, Maren Matthiesen, Nino Fabri and Olga Matthiesen,

Family and guests at Aenny Catzenstein nee Gottschalk's 80th birthday party; London.

Dinner scene with Franz Mattheisen left, daughter Susan Mattheisen next to him, next daughter Maren Matthiesen, his wife Olga Matthiesen at the end of the table. Beatrice Durand is facing the camera

Gottschalk family on vacation; Norderney, Germany.

Left to right: two unidentified women, Kurt Gottschalk, Therese Gottschalk nee Molling, Fritz Gottschalk, unidentified woman (the maid?), and Elizabeth Gottschalk

Gottschalk family on vacation in front of Kurhaus Brunig; Norderney, Germany.

From left to right: man with camera: Karl Gottschalk; sitting on stairs: Fritz Gottschalk, unidentified woman, Therese Gottschalk nee Molling, Hans Ludwig, Kurt Gottschalk, unidentified woman (maid?) and Elizabeth Gottschalk

Family of Dr. Max and Helen Bejach portraits family

unidentified family members

Within-family outliers: Segregating alleles or environmental effects? A linkage analysis of height from 5815 sibling pairs

Most information in linkage analysis for quantitative traits comes from pairs of relatives that are phenotypically most discordant or concordant. Confounding this, within-family outliers from non-genetic causes may create false positives and negatives. We investigated the influence of within-family outliers empirically, using one of the largest genome-wide linkage scans for height. The subjects were drawn from Australian twin cohorts consisting of 8447 individuals in 2861 families, providing a total of 5815 possible pairs of siblings in sibships. A variance component linkage analysis was performed, either including or excluding the within-family outliers. Using the entire dataset, the largest LOD scores were on chromosome 15q (LOD 2.3) and 11q (1.5). Excluding within-family outliers increased the LOD score for most regions, but the LOD score on chromosome 15 decreased from 2.3 to 1.2, suggesting that the outliers may create false negatives and false positives, although rare alleles of large effect may also be an explanation. Several regions suggestive of linkage to height were found after removing the outliers, including 1q23.1 (2.0), 3q22.1 (1.9) and 5q32 (2.3). We conclude that the investigation of the effect of within-family outliers, which is usually neglected, should be a standard quality control measure in linkage analysis for complex traits and may reduce the noise for the search of common variants of modest effect size as well as help identify rare variants of large effect and clinical significance. We suggest that the effect of within-family outliers deserves further investigation via theoretical and simulation studies.