About the power of biostatistics in sibling analysis—comparison of empirical and simulated data

Abstract

The determination of potential sibship is a common task in routine kinship analysis, but often the putative parents are not available for analysis anymore. Then, a sibling analysis has to be conducted investigating only the potential siblings, thus reducing the power of the conclusion. In an attempt to determine meaningfulness of biostatistical calculations, 346 dizygotic twin pairs, 30 confirmed half siblings, and 112 unrelated people (to generate 6216 pair comparisons) were studied, all genetically typed using at least the Powerplex® 16 STRs. From every pair, the probabilities for a full sibship (identical parents) and half sibship (different fathers) were calculated using a commercially available computer program. Additionally, we simulated marker data for one million pairs of full sibs, half sibs, and unrelated persons each. Ninety-five percent of full sibling pairs demonstrated a likelihood ratio (LR) > 9 (W-value > 90 %) and less than 4% of these showed a LR < 3 (W-value < 75%) for full sibship after analysis of 15 STRs. The results for half siblings are less unambiguous. Here, only 57% achieved a LR > 9 and 23% a LR < 3. Regarding the unrelated pairs, more than 90% had a LR < 1/9 and only 2% reached a LR > 9. All in all, our results show that 15 to 20 STRs have sufficient power for analyses in kinship. Moreover, our data provide a statistical basis for the determination of the information content of a LR/W-value in a sibship case. Investigating an identical number of full siblings and unrelated pairs, it could be shown that 92% of pairs with a LR > 9 for full sibship probability really are full siblings. So, setting a cutoff level for full sibship at LR > 9, less than 10% of pairs will be wrongly assumed as full siblings even though they are unrelated.

A novel approach of kinship determination based on the physical length of genetically shared regions of chromosomes

“…Short tandem repeats (STRs) have traditionally been chosen as the primary genetic marker in forensic DNA typing for individual identification and paternity testing (Balding and Nichols 1995 ). These markers can provide sufficient discriminative power for close familial relationships such as paternity or siblings, and increasing the number of markers used can further enhance the reliability of the testing (von Wurmb-Schwark et al 2015 ). However, this STR system is less effective for extended familial relationships such as first-cousins, and the inclusion of more loci in the analysis to increase discriminative power is limited by frequent mutational events of STRs and several loci linkages on the same chromosome (von Wurmb-Schwark et al 2015 ; Tamura et al 2015 ).…”

“…These markers can provide sufficient discriminative power for close familial relationships such as paternity or siblings, and increasing the number of markers used can further enhance the reliability of the testing (von Wurmb-Schwark et al 2015 ). However, this STR system is less effective for extended familial relationships such as first-cousins, and the inclusion of more loci in the analysis to increase discriminative power is limited by frequent mutational events of STRs and several loci linkages on the same chromosome (von Wurmb-Schwark et al 2015 ; Tamura et al 2015 ). Additional genetic markers, such as Y chromosomal STRs and mitochondrial DNA polymorphisms can also serve as supplementary tools, but their applicability is limited in cases involving identification of paternal or maternal lineage.…”